Major interaction on record — check this product against your medications before combining. Based on 46 of 48 ingredients. Check your meds →
Dietary supplement

Neuro-Natural Recall Ingredients & Drug Interactions

by XtendLife

Neuro-Natural Recall label
See full label image
Tablet Or Pill Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 9, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Neuro-Natural Recall against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Major

Neuro-Natural Recall is a dietary supplement by XtendLife with 48 active ingredients. Its ingredients are commonly taken for muscle recovery and sports performance, gut health and 'leaky gut', recovery from severe illness or injury.Based on those ingredients, 1,918 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Tea extract, Ginkgo extract, Quercetin. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Neuro-Natural Recall by XtendLife

Ask about any prescription or over-the-counter medication and we check it for interactions with Neuro-Natural Recall by XtendLife — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
Prefer a human? Send your question to our licensed pharmacists — free, answered by email within 24 hours.
Computed from our clinical databases

HelloPharmacist Scorecard of Neuro-Natural Recall by XtendLife

Four independent checks of what is known — a summary of the available information, not a grade of the product itself.

Evidence for Intended Use
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Not assessable

The stated purpose hasn't been mapped to our evidence data yet.

Why this rating?
  • We haven't mapped this product's purpose to our evidence data yet — it'll be graded on the next content refresh.
Ingredient Transparency
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 48 of its 48 active ingredients.
  • “SAMe” is listed as a grouped ingredient — the label gives one combined amount (149 mg) without saying how much of each component you get.
Known Interaction Concern
Major identified

At least one ingredient has a documented Major-severity interaction. Check your medications for a personalized result.

Why this rating?
  • 39 of the 46 matched ingredients can interact with medications — Milk Thistle, Vinpocetine, Manganese, Bilberry, Lysine, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,919 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.
Safety Information
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 46 of the 46 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 46 of 46.
  • General safety write-ups exist for 46 of 46.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

HelloPharmacist summaryFully disclosed formula with no assessable stated purpose. Major medication interactions have been identified, and safety information is well characterized.

Assessment coverage: 46 of 48 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Apr 25, 2014.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Neuro-Natural Recall, straight from the product label.

Brand XtendLife
Net contents 90 Tablet(s)
Market status Off market
Date entered into DSLD Apr 25, 2014
DSLD ID 32230
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Neuro-Natural Recall by XtendLife, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
6 Tablet(s)
Maximum serving Sizes:
6 Tablet(s)
Servings per container
15
IngredientAmount% DV
Calories25 {Calories}--
L-Glutamine149 mg--
Calories from Fat5 {Calories}--
Folic Acid300 mcg80%
Pantothenic Acid9 mg90%
Thiamine4 mg270%
Biotin1994 mcg660%
L-Methionine99 mg--
L-Lysine Hydrochloride100 mg--
L-Tyrosine300 mg--
Inositol88 mg--
Boron738 mcg--
Vitamin E5 IU20%
Choline Bitartrate299 mg--
Zinc2.5 mg20%
Selenium89 mcg130%
5-HTP148 mg--
Ginkgo extract120 mg--
Green Tea extract75 mg--
Acetyl L-Carnitine150 mg--
Alpha Lipoic Acid150 mg--
Riboflavin3 mg180%
Passionflower extract90 mg--
Eleuthero extract90 mg--
Grape seed extract45 mg--
DL-Phenylalanine238 mg--
Schisandra extract90 mg--
Molybdenum59 mcg80%
Niacin8 mg40%
Chromium35 mcg30%
Lycopene1.1 mg--
Copper0.07 mg4%
Manganese0.08 mg40%
SAMe149 mg--
from 294 mg S-Adenosylmethionine tosylate294 mg--
Piperine15 mg--
Bilberry extract75 mg--
Soy Lecithin300 mg--
Betain HCL148 mg--
Milk Thistle extract120 mg--
Hawthorn extract75 mg--
Quercetin150 mg--
Vitamin B610 mg500%
Bacopa extract250 mg--
Huperzine A300 mcg--
Lithium37 mcg--
Gotu kola extract225 mg--
Yucca extract90 mg--
Phosphatidyl serine24 mg--
Vinpocetine15 mg--
RNA75 mg--

Other ingredients: Microcrystalline Cellulose, Dextrose, Enteric Coating, Silicon Dioxide, Magnesium Stearate, Dicalcium Phosphate, Maltodextrin

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
General Statements

Not a significant source of Calcium.

love life. live life.

Batch number: Manufactured: Use by date:

Made in New Zealand

With Ingredients to Help Support Memory

Enteric coated

General

L1078-8

Brand IP Statement(s)

Xtend-Life(TM) Neuro-Natural Recall is an all-natural professional supplement formulated to include ingredients specifically chosen to help support memory function*.

FDA Statement of Identity

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Dietary Supplement

Seals/Symbols

BEST QUALITY GUARANTEE

Formula

Contains ingredients derived from soy

Precautions

Contains ingredients derived from soy

Storage

Store in a cool, dry place.

Formulation

Does not contain dairy, gluten, shellfish or peanut

Suggested/Recommended/Usage/Directions

Directions For Use Adults: 6 tablets per day Age 16-18 years: 4 tablets per day Age 12-15 years: 3 tablets per day Age 10-11 years: 2 tablets per day For optimal results split into 2 doses per day; first thing in the morning, and around mid to late afternoon.

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Neuro-Natural Recall by XtendLife label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

Neuro-Natural Recall label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Neuro-Natural Recall by XtendLife

These are the 48 active ingredients this product is made of. Select any to open its full monograph.

Serving size6 Tablet(s) Dosage formTablet Or Pill Servings per container15 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

L-Glutamine

Interacts with
50 drugs
149 mg per serving

Glutamine is the most abundant amino acid in the body and is usually made in your muscles. A prescription form is FDA-approved to help reduce sickle c...

L-Glutamine monograph & interactions

Folic Acid

Interacts with
40 drugs
300 mcg per serving

Folic acid is the man-made form of vitamin B9 and is one of the most well-studied supplements, especially for preventing serious birth defects when ta...

Folic Acid monograph & interactions

Pantothenic Acid

No known
interactions
9 mg per serving Form: Calcium Pantothenate

Pantothenic acid is vitamin B5, an essential nutrient your body uses to turn food into energy. True deficiency is very rare because it is found in nea...

Pantothenic Acid monograph & interactions

Thiamine

Interacts with
3 drugs
4 mg per serving Form: Thiamine Hydrochloride

Thiamine (vitamin B1) is an essential nutrient your body needs to turn food into energy and to keep your nerves and heart healthy. Most people get eno...

Thiamine monograph & interactions

Biotin

No known
interactions
1994 mcg per serving

Biotin (vitamin B7) is a water-soluble vitamin your body needs to turn food into energy and to support healthy hair, skin, and nails. Most people get...

Biotin monograph & interactions

L-Methionine

No known
interactions
99 mg per serving

Methionine is an essential amino acid that your body needs for protein building and many basic chemical reactions. Most people get enough from a norma...

L-Methionine monograph & interactions

L-Lysine Hydrochloride

Interacts with
1 drug
100 mg per serving

Lysine is an essential amino acid your body cannot make on its own, so it must come from food or supplements. People most often take extra lysine to t...

L-Lysine Hydrochloride monograph & interactions

L-Tyrosine

Interacts with
21 drugs
300 mg per serving

L-tyrosine is an amino acid your body uses to make brain chemicals like dopamine and norepinephrine. Some studies suggest it may help mental performan...

L-Tyrosine monograph & interactions

Inositol

Interacts with
86 drugs
88 mg per serving

Inositol is a sugar alcohol made naturally in the body and found in many foods, and it is sold as a supplement (often myo-inositol) mainly for PCOS, m...

Inositol monograph & interactions

Boron

No known
interactions
738 mcg per serving Form: Boron Citrate

Boron is a trace mineral found in many plant foods and sold as a supplement, mainly promoted for bone, joint, and hormone health. The human evidence f...

Boron monograph & interactions

Vitamin E

Interacts with
764 drugs
5 IU per serving Form: D-Alpha-Tocopheryl Succinate

Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correc...

Vitamin E monograph & interactions

Choline Bitartrate

Interacts with
16 drugs
299 mg per serving

Choline is an essential nutrient your body needs for liver function, brain health, and nerve signaling, and many people get enough from foods like egg...

Choline Bitartrate monograph & interactions

Zinc

Interacts with
67 drugs
2.5 mg per serving Form: Zinc Citrate

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but suppleme...

Zinc monograph & interactions

Selenium

Interacts with
321 drugs
89 mcg per serving Form: L-Selenomethionine

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who...

Selenium monograph & interactions

5-HTP

Interacts with
398 drugs
148 mg per serving Form: Griffonia simplicifolia

5-HTP is a compound your body uses to make serotonin, and people take it as a supplement hoping to improve mood, sleep, and headaches. Some early rese...

5-HTP monograph & interactions

Ginkgo extract

Interacts with
1,266 drugs
120 mg per serving

Ginkgo is one of the world's most popular herbal supplements, mostly taken to support memory and circulation. The evidence for these uses is mixed and...

Ginkgo extract monograph & interactions

Green Tea extract

Interacts with
1,293 drugs
75 mg per serving

Green tea is a popular beverage rich in antioxidants called catechins, and drinking it in normal amounts is considered safe for most people. Concentra...

Green Tea extract monograph & interactions

Acetyl L-Carnitine

Interacts with
203 drugs
150 mg per serving

Acetyl-L-carnitine is a form of the amino acid carnitine that the body uses to help produce energy in cells. It is most studied for nerve pain and mem...

Acetyl L-Carnitine monograph & interactions

Alpha Lipoic Acid

Interacts with
263 drugs
150 mg per serving

Alpha-lipoic acid (ALA) is an antioxidant made naturally by the body and found in small amounts in foods. It is most studied for diabetic nerve pain,...

Alpha Lipoic Acid monograph & interactions

Riboflavin

Interacts with
20 drugs
3 mg per serving Form: Riboflavin 5-Phosphate

Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally...

Riboflavin monograph & interactions

Passionflower extract

Interacts with
836 drugs
90 mg per serving

Passion flower is a traditional calming herb that many people use for anxiety and sleep. Early studies hint it may help with mild anxiety and restless...

Passionflower extract monograph & interactions

Eleuthero extract

Interacts with
1,140 drugs
90 mg per serving

Eleuthero is an herb traditionally used as an 'adaptogen' to fight fatigue, boost energy, and help the body handle stress. The scientific evidence beh...

Eleuthero extract monograph & interactions

Grape seed extract

Interacts with
910 drugs
45 mg per serving

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and b...

Grape seed extract monograph & interactions

DL-Phenylalanine

238 mg per serving

Schisandra extract

Interacts with
803 drugs
90 mg per serving

Schisandra is a traditional Chinese medicine berry used as an adaptogen for stress, fatigue, and liver support. Human evidence is limited and most cla...

Schisandra extract monograph & interactions

Molybdenum

No known
interactions
59 mcg per serving Form: Sodium Molybdate

Molybdenum is an essential trace mineral your body needs in tiny amounts to help certain enzymes work. Most people get enough from a normal diet, so s...

Molybdenum monograph & interactions

Niacin

Interacts with
727 drugs
8 mg per serving Form: Chromium Nicotinate, Niacinamide

Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescr...

Niacin monograph & interactions

Chromium

Interacts with
178 drugs
35 mcg per serving Form: Chromium Nicotinate

Chromium is an essential trace mineral involved in how the body handles sugar and fat. Some studies suggest it may modestly help blood sugar control i...

Chromium monograph & interactions

Lycopene

Interacts with
122 drugs
1.1 mg per serving Form: Tomato

Lycopene is a red plant pigment and antioxidant found mainly in tomatoes and other red fruits. Eating lycopene-rich foods is linked with possible hear...

Lycopene monograph & interactions

Copper

Interacts with
31 drugs
0.07 mg per serving Form: Copper Gluconate

Copper is an essential trace mineral your body needs in small amounts for making red blood cells, supporting nerves and bones, and helping enzymes wor...

Copper monograph & interactions

Manganese

Interacts with
83 drugs
0.08 mg per serving Form: Manganese Citrate

Manganese is an essential trace mineral your body needs in small amounts for bone formation, metabolism, and antioxidant defense, and most people get...

Manganese monograph & interactions

SAMe

Interacts with
189 drugs
149 mg per serving

SAM-e is a compound your body makes naturally that is sold as a supplement, most often for depression and osteoarthritis. Some research suggests it ma...

SAMe monograph & interactions

Piperine

Interacts with
1,019 drugs
15 mg per serving Form: Black Pepper

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to he...

Piperine monograph & interactions

Bilberry extract

Interacts with
275 drugs
75 mg per serving

Bilberry is a blueberry-like fruit rich in antioxidant plant compounds called anthocyanins, and it has a long history of traditional use for eye healt...

Bilberry extract monograph & interactions

Soy Lecithin

No known
interactions
300 mg per serving

Lecithin is a natural fatty substance found in foods and made by the body that is widely used as a supplement and food emulsifier. Evidence supporting...

Soy Lecithin monograph & interactions

Betain HCL

Interacts with
36 drugs
148 mg per serving

Betaine hydrochloride is a supplement used to temporarily increase stomach acid in people who may have low acid levels. Evidence for its benefits is l...

Betain HCL monograph & interactions

Milk Thistle extract

Interacts with
954 drugs
120 mg per serving

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin....

Milk Thistle extract monograph & interactions

Hawthorn extract

Interacts with
191 drugs
75 mg per serving

Hawthorn is a plant traditionally used for heart-related complaints, and some studies suggest it may modestly help symptoms of mild heart failure when...

Hawthorn extract monograph & interactions

Quercetin

Interacts with
1,169 drugs
150 mg per serving Form: Saphorae japonica

Quercetin is a plant flavonoid with antioxidant and anti-inflammatory properties found in many common foods and sold as a supplement. While early rese...

Quercetin monograph & interactions

Vitamin B6

Interacts with
210 drugs
10 mg per serving Form: Pyridoxal 5-Phosphate

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is b...

Vitamin B6 monograph & interactions

Bacopa extract

Interacts with
930 drugs
250 mg per serving

Bacopa is an Ayurvedic herb most often used for memory and thinking. Some small studies suggest it may modestly help memory when taken regularly for s...

Bacopa extract monograph & interactions

Huperzine A

Interacts with
219 drugs
300 mcg per serving Form: Lyopodium serrata

Huperzine A is a purified compound from a Chinese clubmoss that acts like a mild cholinesterase inhibitor, similar in mechanism to some prescription A...

Huperzine A monograph & interactions

Lithium

Interacts with
515 drugs
37 mcg per serving Form: Lithium Carbonate

Lithium is a naturally occurring metal that, in prescription form (lithium carbonate or citrate), is an FDA-approved, well-proven treatment for bipola...

Lithium monograph & interactions

Gotu kola extract

Interacts with
579 drugs
225 mg per serving

Gotu kola is a traditional Ayurvedic and Asian herb that people use for wound healing, circulation, skin problems, and as a calming or memory-supporti...

Gotu kola extract monograph & interactions

Yucca extract

No known
interactions
90 mg per serving Form: Yucca schidigera

Yucca is a desert plant traditionally used for joint pain, arthritis, and digestion, and it contains compounds called saponins thought to have anti-in...

Yucca extract monograph & interactions

Phosphatidyl serine

Interacts with
219 drugs
24 mg per serving Form: Soy bean

Phosphatidylserine is a natural fat-like compound found in cell membranes, especially in the brain, and it is sold mainly to support memory and thinki...

Phosphatidyl serine monograph & interactions

Vinpocetine

Interacts with
208 drugs
15 mg per serving Form: Criocerus longiflorus

Vinpocetine is a lab-made compound based on a chemical from the periwinkle plant, and it is marketed mainly for memory and brain health. The evidence...

Vinpocetine monograph & interactions

RNA

75 mg per serving

Other (inactive) ingredients: Microcrystalline Cellulose, Dextrose, Enteric Coating, Silicon Dioxide, Magnesium Stearate, Dicalcium Phosphate, Maltodextrin. These complete the product’s ingredient list but are not active constituents.

Interaction report

Neuro-Natural Recall by XtendLife Drug Interactions

Neuro-Natural Recall contains 48 ingredients, and 39 of them have known drug interactions. Altogether they interact with 1,918 medications. Here’s the picture, then you can look up your own drug.

Want to check YOUR meds against Neuro-Natural Recall?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

 Go to the checker
1,918Drugs
285 Major 1,620 Moderate 13 Minor

Ingredients driving the most interactions

Green Tea extract 1,293
Ginkgo extract 1,266
Quercetin 1,169
Eleuthero extract 1,140
Piperine 1,019

Individual Drug Interactions

The ingredients in Neuro-Natural Recall interact with 1,918 drugs. Click any drug to see the details.

39 of the 48 ingredients in Neuro-Natural Recall interact with drugs. Each result below shows which ingredient is responsible. Green Tea extract Ginkgo extract Quercetin Eleuthero extract Piperine Milk Thistle extract Bacopa extract Grape seed extract Passionflower extract Schisandra extract Vitamin E Niacin Gotu kola extract Lithium 5-HTP Selenium Bilberry extract Alpha Lipoic Acid Huperzine A Phosphatidyl serine Vitamin B6 Vinpocetine Acetyl L-Carnitine Hawthorn extract SAMe Chromium Lycopene Inositol Manganese Zinc L-Glutamine Folic Acid Betain HCL Copper L-Tyrosine Riboflavin Choline Bitartrate Thiamine L-Lysine Hydrochloride

Each ingredient & the kinds of drugs it affects

For each ingredient in Neuro-Natural Recall with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Green Tea extract58 drug types · 1,293 drugs

Atorvastatin (Lipitor)

Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected. Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin. It is not clear if drinking green tea alters the absorption of atorvastatin.

Likelihood Likely Evidence B
Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Green tea contains caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death.

Likelihood Probable Evidence D
Nadolol (Corgard)

Green tea seems to reduce the levels and clinical effects of nadolol.
Preliminary clinical research shows that green tea consumption reduces plasma concentrations of nadolol. Compared to a control group, both peak levels and total drug exposure (AUC) of nadolol were reduced by approximately 85% in subjects who drank green tea daily for two weeks. Drinking green tea with nadolol also significantly reduced nadolol's systolic blood pressure lowering effect. Other clinical research shows that a single dose of green tea can affect plasma nadolol levels for at least one hour. Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is involved in the uptake of nadolol in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Likelihood Likely Evidence B
5-Fluorouracil

Theoretically, high doses of green tea might increase the effects and side effects of 5-fluorouracil.
Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425%.

Likelihood Possible Evidence D
Adenosine (Adenocard)

Theoretically, green tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Green tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine doesn't seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup. Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea. However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity.

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Bortezomib (Velcade)

Theoretically, green tea might interfere with the effects of bortezomib.
In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines. Advise patients taking bortezomib, not to take green tea.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg. Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals.

Likelihood Possible Evidence D
Celiprolol (Celicard)

Theoretically, green tea might reduce the levels and clinical effects of celiprolol.
In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98%. This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Likelihood Possible Evidence D
Cimetidine (Tagamet)

Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.
Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels. Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine.

Likelihood Possible Evidence B
Contraceptive Drugs

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.
Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65%.

Likelihood Probable Evidence B
Cytochrome P450 1A2 (Cyp1A2) Inhibitors

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2),. Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from green tea and increase caffeine levels.

Likelihood Possible Evidence D
Dipyridamole (Persantine)

Theoretically, green tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Green tea contains caffeine. Caffeine might inhibit dipyridamole-induced vasodilation. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Likelihood Probable Evidence B
Disulfiram (Antabuse)

Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
In human research, disulfiram decreases the clearance and increases the half-life of caffeine.

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.
Green tea contains caffeine. In excessive amounts, caffeine can reduce potassium levels due to stimulation of the sodium-potassium pump. Diuretics can also cause lower potassium levels.

Likelihood Possible Evidence D
Estrogens

Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, green tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Felbamate (Felbatol)

Theoretically, green tea might reduce the effects of felbamate and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Fexofenadine (Allegra)

Green tea can decrease blood levels of fexofenadine.
Clinical research shows that green tea can significantly decrease blood levels and excretion of fexofenadine. Taking green tea extract with a dose of fexofenadine decreased bioavailability of fexofenadine by about 30%. In vitro, green tea inhibits the cellular accumulation of fexofenadine by inhibiting the organic anion transporting polypeptide (OATP) drug transporter. Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates.

Likelihood Probable Evidence B
Flutamide (Eulexin)

Theoretically, green tea might increase the levels and adverse effects of flutamide.
Green tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk adverse effects.

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Fluvoxamine reduces caffeine metabolism.

Likelihood Probable Evidence D
Hepatotoxic Drugs

Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Green tea extract supplements have been linked to several cases of hepatotoxicity and might have additive hepatotoxic effects with other drugs..

Likelihood Unlikely Evidence D
Imatinib (Gleevec)

Theoretically, green tea might reduce the levels and clinical effects of imatinib.
In animal research, a single dose of green tea extract reduces the area under the curve (AUC) of imatinib by up to approximately 64% and its main metabolite N-desmethyl imatinib by up to approximately 81%. This interaction has not been shown in humans. The mechanism of action is unclear but may involve multiple pathways.

Likelihood Possible Evidence D
Green Tea extract full monograph & all 58 interactions

Ginkgo extract23 drug types · 1,266 drugs

Talinolol

Taking ginkgo with talinolol seems to increase blood levels of talinolol.
There is some evidence that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of talinolol by 36% in healthy male individuals. However, single doses of ginkgo do not seem to affect talinolol pharmacokinetics.

Likelihood Probable Evidence B
Alprazolam (Xanax)

Theoretically, ginkgo might decrease the levels and clinical effects of alprazolam.
In clinical research, ginkgo extract (Ginkgold) 120 mg twice daily seems to decrease alprazolam levels by about 17%. However, ginkgo does not appear to decrease the elimination half-life of alprazolam. This suggests that ginkgo is more likely to decrease absorption of alprazolam rather than induce hepatic metabolism of alprazolam.

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin. Theoretically, ginkgo might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. However, population and clinical studies have produced mixed results. Some evidence shows that short-term use of ginkgo leaf does not significantly reduce platelet aggregation and blood clotting. A study in healthy males who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days found no change in prothrombin time. An analysis of a large medical record database suggests that ginkgo increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin. It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation. However, a meta-analysis of 18 studies using standardized ginkgo extracts, 80-480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. In addition, a single dose of ginkgo plus clopidogrel or ticlopidine does not seem to significantly increase bleeding time or platelet aggregation. Also, taking ginkgo leaf extract daily for 8 days in conjunction with rivaroxaban does not affect anti-factor Xa activity; however, this study did not evaluate bleeding time.

Likelihood Possible Evidence A
Anticonvulsants

Theoretically, ginkgo might reduce the effectiveness of anticonvulsants.
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves. Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity. However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking ginkgo with antidiabetes drugs might alter the response to antidiabetes drugs.
Ginkgo leaf extract seems to alter insulin secretion and metabolism, and might affect blood glucose levels in people with type 2 diabetes. The effect of ginkgo seems to differ depending on the insulin and treatment status of the patient. In diet-controlled diabetes patients with hyperinsulinemia, taking ginkgo does not seem to significantly affect insulin or blood glucose levels. In patients with hyperinsulinemia who are treated with oral hypoglycemic agents, taking ginkgo seems to decrease insulin levels and increase blood glucose following an oral glucose tolerance test. Researchers speculate that this could be due to ginkgo-enhanced hepatic metabolism of insulin. In patients with pancreatic exhaustion, taking ginkgo seems to stimulate pancreatic beta-cells, resulting in increased insulin and C-peptide levels, but with no significant change in blood glucose levels in response to an oral glucose tolerance test.

Likelihood Possible Evidence B
Atorvastatin (Lipitor)

Theoretically, ginkgo might decrease the levels and clinical effects of atorvastatin.
In humans, intake of ginkgo extract appears to increase atorvastatin clearance, reducing the area under the curve of atorvastatin by 10% to 14% and the maximum concentration by 29%. However, this interaction does not appear to affect cholesterol synthesis and absorption. Further, a model in rats with hyperlipidemia suggests that administering ginkgo extract does not impact blood levels of atorvastatin and leads to lower total cholesterol, low-density lipoprotein cholesterol, and triglycerides when compared with rats given atorvastatin alone.

Likelihood Probable Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, ginkgo might increase levels of drugs metabolized by CYP1A2.
Laboratory research suggests that ginkgo leaf extract can mildly inhibit CYP1A2 enzymes. However, clinical research suggests ginkgo might not affect CYP1A2. Until more is known, use ginkgo cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Possible Evidence B
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.
Some clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce CYP2C19 enzymes and potentially decrease levels of drugs metabolized by these enzymes. However, other clinical research shows that taking ginkgo 120 mg twice daily for 12 days has no effect on levels of drugs metabolized by CYP2C19.

Likelihood Probable Evidence B
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, ginkgo might increase levels of drugs metabolized by CYP2C9.
In vitro, a specific standardized extract of ginkgo leaf (EGb 761) inhibits CYP2C9 activity . The terpenoid (ginkgolides) and flavonoid (quercetin, kaempferol, etc.) constituents seem to be responsible for this effect. Most ginkgo extracts contain some amount of these constituents. Therefore, other ginkgo leaf extracts might also inhibit the CYP2C9 enzyme. However, clinical research suggests that ginkgo might not have a significant effect on CYP2C9 in humans. Ginkgo does not seem to significantly affect the pharmacokinetics of CYP2C9 substrates diclofenac or tolbutamide.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP3A4.
There is conflicting evidence about whether ginkgo induces or inhibits CYP3A4. Ginkgo does not appear to affect hepatic CYP3A4. However, it is not known if ginkgo affects intestinal CYP3A4. Preliminary clinical research suggests that taking ginkgo does not significantly affect levels of donepezil, lopinavir, or ritonavir, which are all CYP3A4 substrates. Other clinical research also suggests ginkgo does not significantly affect CYP3A4 activity. However, there are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4).

Likelihood Possible Evidence B
Efavirenz (Sustiva)

Theoretically, ginkgo might decrease the levels and clinical effects of efavirenz.
There are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. In one case, an HIV-positive male experienced over a 50% decrease in efavirenz levels over the course of 14 months while taking ginkgo extract. HIV-1 RNA copies also increased substantially, from less than 50 to more than 1500. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4). In another case report, a patient stable on antiviral therapy including efavirenz for 10 years, had an increase in viral load from <50 copies/mL to 1350 copies/mL after 2 months of taking a combination of supplements including ginkgo. After stopping ginkgo, the viral load was again controlled with the same antiviral therapy regimen.

Likelihood Possible Evidence D
Ibuprofen (Advil, Others)

Theoretically, ginkgo might increase the risk of bleeding when used with ibuprofen.
Ginkgo might have antiplatelet effects and has been associated with several case reports of spontaneous bleeding. In one case, a 71-year-old male had taken a specific ginkgo extract (Gingium, Biocur) 40 mg twice daily for 2.5 years. About 4 weeks after starting ibuprofen 600 mg daily he experienced a fatal intracerebral hemorrhage. However, the antiplatelet effects of ginkgo have been questioned. A meta-analysis and other studies have not found a significant antiplatelet effect with standardized ginkgo extracts, 80 mg to 480 mg taken daily for up to 32 weeks.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, taking ginkgo with P-glycoprotein substrates might increase the levels and adverse effects of these substrates.
A small clinical study in healthy volunteers shows that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of the P-glycoprotein substrate, talinolol, by 36% in healthy male individuals. However, single doses of ginkgo do not have the same effect.

Likelihood Possible Evidence B
Risperidone (Risperdal)

Theoretically, taking ginkgo with risperidone might increase the levels and adverse effects of risperidone.
A single case of priapism has been reported for a 26-year-old male with schizophrenia who used risperidone 3 mg daily along with ginkgo extract 160 mg daily. Risperidone is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4. CYP3A4 activity might be affected by ginkgo. Theoretically, ginkgo may inhibit the metabolism of risperidone and increase the risk of adverse effects.

Likelihood Possible Evidence D
Rosiglitazone (Avandia)

Theoretically, ginkgo might decrease the levels and clinical effects of rosiglitazone.
Animal research shows that ginkgo leaf extract orally 100 or 200 mg/kg daily for 10 days alters the pharmacodynamics of rosiglitazone in a dose-dependent manner. The 100 mg/kg and 200 mg/kg doses reduce the area under the concentration time curve (AUC) of rosiglitazone by 39% and 52%, respectively, and the half-life by 28% and 39%, respectively. It is hypothesized that these changes may be due to induction of cytochrome P450 2C8 by ginkgo.

Likelihood Possible Evidence D
Seizure Threshold Lowering Drugs

Theoretically, taking ginkgo with drugs that lower the seizure threshold might increase the risk for convulsions.
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves. Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity. However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy.

Likelihood Possible Evidence D
Simvastatin (Zocor)

Theoretically, ginkgo might decrease the levels and clinical effects of simvastatin.
Clinical research shows that taking ginkgo extract can reduce the area under the curve and maximum concentration of simvastatin by 32% to 39%. However, ginkgo extract does not seem to affect the cholesterol-lowering ability of simvastatin.

Likelihood Probable Evidence B
Sofosbuvir (Sovaldi)

Theoretically, ginkgo might increase the levels and clinical effects of sofosbuvir.
Animal research in rats shows that giving a ginkgo extract 25 mg/kg orally daily for 14 days increases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 11%, increases the half-life by 60%, and increases the plasma concentration at 4 hours by 38%. This interaction appears to be related to the inhibition of intestinal P-glycoprotein by ginkgo.

Likelihood Possible Evidence D
Tacrolimus (Prograf)

Theoretically, ginkgo might increase the blood levels of tacrolimus.
In vitro evidence suggests that certain biflavonoids in ginkgo leaves (i.e. amentoflavone, ginkgetin, bilobetin) may inhibit the metabolism of tacrolimus by up to 50%. This interaction appears to be time-dependent and due to inhibition of cytochrome P450 (CYP) 3A4 by these bioflavonoids. In rats given tacrolimus 1 mg/kg orally, amentoflavone was shown to increase the area under the concentration time curve (AUC) of tacrolimus by 3.8-fold.

Likelihood Possible Evidence D
Trazodone (Desyrel)

Theoretically, ginkgo might increase the levels and clinical effects of trazodone.
In a case report, an Alzheimer patient taking trazodone 20 mg twice daily and ginkgo leaf extract 80 mg twice daily for four doses became comatose. The coma was reversed by administration of flumazenil (Romazicon). Coma might have been induced by excessive GABA-ergic activity. Ginkgo flavonoids are thought to have GABA-ergic activity and act directly on benzodiazepine receptors. Ginkgo might also increase metabolism of trazodone to active GABA-ergic metabolites, possibly by inducing cytochrome P450 3A4 (CYP3A4) metabolism.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. Information from a medical database suggests that when taken concurrently with warfarin, ginkgo increases the risk of a bleeding adverse event by 38%. There is also some evidence that ginkgo leaf extract can inhibit cytochrome P450 2C9, an enzyme that metabolizes warfarin. This could result in increased warfarin levels. However, population and clinical research has produced mixed results. Clinical research in healthy people suggests that ginkgo has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. A meta-analysis of 18 studies using standardized ginkgo extracts, 80 mg to 480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. There is also some preliminary clinical research that suggests ginkgo might not significantly increase the effects of warfarin in patients that have a stable INR.

Likelihood Possible Evidence B
Nifedipine (Procardia)

Theoretically, taking ginkgo with oral, but not intravenous, nifedipine might increase levels and adverse effects of nifedipine.
Animal research and some clinical evidence suggests that taking ginkgo leaf extract orally in combination with oral nifedipine might increase nifedipine levels and cause increased side effects, such as headaches, dizziness, and hot flushes. However, taking ginkgo orally does not seem to affect the pharmacokinetics of intravenous nifedipine.

Likelihood Possible Evidence B
Omeprazole (Prilosec)

Theoretically, taking ginkgo with omeprazole might decrease the levels and clinical effects of omeprazole.
Clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce cytochrome P450 (CYP) 2C19 enzymes and decrease levels of omeprazole by about 27% to 42%.

Likelihood Possible Evidence B
Ginkgo extract full monograph & interactions

Quercetin21 drug types · 1,169 drugs

Antidiabetes Drugs

Theoretically, concomitant use of quercetin and antidiabetes drugs might increase the risk of hypoglycemia.

Clinical research suggests that a combination of quercetin, myricetin, and chlorogenic acid reduce levels of fasting glucose in patients with type 2 diabetes, including those already taking antidiabetes agents. The effect of quercetin alone is unknown.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking quercetin with antihypertensive drugs might increase the risk of hypotension.

Quercetin can modestly decrease blood pressure in people with mild hypertension. Theoretically, it might have additive blood pressure lowering effects when used with antihypertensive drugs.

Likelihood Possible Evidence B
Cyclosporine (Neoral, Sandimmune)

Theoretically, concomitant use might increase the levels and adverse effects of cyclosporine.

A small study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine, possibly due to inhibition of p-glycoprotein or cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporin.

Likelihood Possible Evidence B
Cytochrome P450 2C8 (Cyp2C8) Substrates

Theoretically, concomitant use might increase the levels and adverse effects of CYP2C8 substrates.

In vitro research shows that quercetin inhibits CYP2C8. Inhibition of paclitaxel (Taxol) metabolism via CYP2C8 has been reported in vitro. However, a small study in humans found no effect of quercetin on rosiglitazone (Avandia), which is also a CYP2C8 substrate.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, concomitant use might increase the levels and adverse effects of CYP2C9 substrates.

A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac, a CYP2C9 substrate, increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5%. Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar), a substrate of CYP2C9. Furthermore, laboratory research shows that quercetin inhibits CYP2C9.

Likelihood Possible Evidence B
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, concomitant use might increase the levels and adverse effects of CYP2D6 substrates.

In vitro research show that quercetin inhibits CYP2D6. This effect has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, concomitant use might alter the effects and adverse effects of CYP3A4 substrates.
A small clinical study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine (Neoral, Sandimmune), a substrate of CYP3A4. Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) and quetiapine (Seroquel), substrates of CYP3A4. Other laboratory research also shows that quercetin inhibits CYP3A4. However, one clinical study shows that quercetin can increase the metabolism of midazolam, a substrate of CYP3A4, and decrease serum concentrations of midazolam by about 24% in some healthy individuals, suggesting possible induction of CYP3A4.

Likelihood Possible Evidence D
Diclofenac (Voltaren, Others)

Theoretically, concomitant use might increase the levels and adverse effects of diclofenac.

A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5%. This is thought to be due to inhibition of CYP2C9 by quercetin.

Likelihood Probable Evidence B
Losartan (Cozaar)

Theoretically, concomitant use might increase the effects and adverse effects of losartan and decrease the effects of its active metabolite.

Animal research shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) while decreasing plasma levels of losartan's active metabolite. This metabolite, which is around 10-fold more potent than losartan, is the result of cytochrome P450 (CYP) 2C9- and CYP3A4-mediated transformation of losartan. Additionally, in vitro research shows that quercetin may inhibit P-glycoprotein-mediated efflux of losartan from the intestines, resulting in increased absorption of losartan. These results suggest that concomitant use of quercetin and losartan might increase systemic exposure to losartan while also decreasing plasma concentrations of losartan's active and more potent metabolite.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, concomitant use might decrease the levels and effects of midazolam.

A small clinical study in healthy volunteers shows that quercetin can increase the metabolism of midazolam, with a decrease in AUC of about 24%.

Likelihood Possible Evidence B
Mitoxantrone

Theoretically, quercetin might increase the effects and adverse effects of mitoxantrone.
In vitro research shows that quercetin increases the intracellular accumulation and cytotoxicity of mitoxantrone, possibly through inhibition of breast cancer resistance protein (BCRP), of which mitoxantrone is a substrate. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Organic Anion Transporter 1 (Oat1) Substrates

Theoretically, concomitant use might increase the effects and adverse effects of OAT1 substrates.

In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT1, with half-maximal inhibitory concentration (IC50) values less than 10 mcM. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Organic Anion Transporter 3 (Oat3) Substrates

Theoretically, concomitant use might increase the effects and adverse effects of OAT3 substrates.

In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT3, with half-maximal inhibitory concentration (IC50) values as low as 0.75 mcM. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Theoretically, concomitant use might increase the effects and adverse effects of OATP substrates.

In vitro evidence shows that quercetin can inhibit organic anion-transporting peptide (OATP) 1B1-mediated uptake of estrone-3-sulfate and pravastatin. Furthermore, clinical research in healthy males shows that intake of quercetin along with pravastatin increases the AUC of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Theoretically, concomitant use might alter the effects and adverse effects of P-glycoprotein substrates.

There is preliminary evidence that quercetin inhibits the gastrointestinal P-glycoprotein efflux pump, which might increase the bioavailability and serum levels of drugs transported by the pump. A small study in healthy volunteers reported that pretreatment with quercetin increased bioavailability and plasma levels after a single dose of cyclosporine (Neoral, Sandimmune). Also, two small studies have shown that quercetin might decrease the absorption of talinolol, a substrate transported by the gastrointestinal P-glycoprotein efflux pump. However, in another small study, several days of quercetin treatment did not significantly affect the pharmacokinetics of saquinavir (Invirase). The reason for these discrepancies is not entirely clear. Until more is known, use quercetin cautiously in combination with P-glycoprotein substrates.

Likelihood Possible Evidence B
Pravastatin (Pravachol)

Theoretically, concomitant use might increase the effects and adverse effects of pravastatin.
In vitro evidence shows that quercetin can inhibit OATP 1B1-mediated uptake of pravastatin. Also, preliminary clinical research in healthy males shows that intake of quercetin along with pravastatin increases the maximum concentration of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells.

Likelihood Possible Evidence B
Prazosin (Minipress)

Theoretically, quercetin might increase the effects and adverse effects of prazosin.
In vitro research shows that quercetin inhibits the transcellular efflux of prazosin, possibly through inhibition of breast cancer resistance protein (BCRP), of which prazosin is a substrate. BCRP is an ATP-binding cassette efflux transporter in the intestines, kidneys, and liver. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Quetiapine (Seroquel)

Theoretically, concomitant use might increase the effects and adverse effects of quetiapine.
Animal research shows that pretreatment with quercetin can increase plasma levels of quetiapine and prolong its clearance, possibly due to inhibition of cytochrome P450 3A4 (CYP3A4) by quercetin. Additionally, the brain-to-plasma ratio of quetiapine concentrations increased, possibly due to inhibition of P-glycoprotein at the blood-brain barrier. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, concomitant use might inhibit the effects of quinolone antibiotics.
In vitro, quercetin binds to the DNA gyrase site on bacteria, which may interfere with the activity of quinolone antibiotics.

Likelihood Possible Evidence B
Sulfasalazine (Azulfidine)

Theoretically, quercetin might increase the effects and adverse effects of sulfasalazine.
Animal research shows that quercetin increases the maximum serum concentration (Cmax) and area under the curve (AUC) of sulfasalazine, possibly through inhibition of breast cancer resistance protein (BCRP), of which sulfasalazine is a substrate. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, quercetin may increase the risk of bleeding if used with warfarin.
Animal and in vitro studies show that quercetin might increase serum levels of warfarin. Quercetin and warfarin have the same human serum albumin (HSA) binding site, and in vitro research shows that quercetin has stronger affinity for the HSA binding site and can theoretically displace warfarin, causing higher serum levels of warfarin. Animal research shows that taking quercetin for 2 weeks before initiating warfarin increases the maximum serum level of warfarin by 30%, the half-life by 10%, and the overall exposure by 63% when compared with control. Concomitant administration of quercetin and warfarin, without quercetin pre-treatment, also increased these measures, but to a lesser degree. Researchers theorize that inhibition of CYP3A4 by quercetin may explain these effects. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Quercetin full monograph & interactions

Eleuthero extract10 drug types · 1,140 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation. Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding. This effect has not been reported in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.
Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals. A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels. However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo. These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

Likelihood Possible Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2. This effect has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9. This effect has not been reported in humans.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Eleuthero might increase serum digoxin levels and increase the risk of side effects.
In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal. It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay. Although the product was found to be free of digoxin and digitoxin, it was not tested for other contaminants.

Likelihood Unlikely Evidence D
Immunosuppressants

Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.
Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, eleuthero might increase levels of P-glycoprotein substrates.
In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein. However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism.

Likelihood Unlikely Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism.

Likelihood Unlikely Evidence B
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.
In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1. Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

Likelihood Possible Evidence D
Eleuthero extract full monograph & interactions

Piperine17 drug types · 1,019 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation. This has not been reported in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Likelihood Possible Evidence D
Atorvastatin (Lipitor)

Theoretically, black pepper might increase blood levels of atorvastatin.
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold. This has not been reported in humans.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, black pepper might increase the effects and side effects of cyclosporine.
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine. This has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
In vitro research suggests that some constituents of black pepper inhibit CYP2D6. This has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research and pharmacokinetic simulation data suggest that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.

Likelihood Possible Evidence D
Lithium

Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
Black pepper is thought to have diuretic properties.

Likelihood Probable Evidence D
Nevirapine (Viramune)

Black pepper might increase blood levels of nevirapine.
Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study.

Likelihood Probable Evidence D
P-Glycoprotein Substrates

Theoretically, black pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein.

Likelihood Possible Evidence D
Pentobarbital (Nembutal)

Theoretically, black pepper might increase the sedative effects of pentobarbital.
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

Black pepper might increase blood levels of phenytoin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin. Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin. Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper.

Likelihood Possible Evidence B
Propranolol (Inderal)

Black pepper might increase blood levels of propranolol.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol.

Likelihood Possible Evidence B
Rifampin (Rifadin)

Black pepper might increase blood levels of rifampin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and serum levels of rifampin.

Likelihood Possible Evidence B
Theophylline

Black pepper might increase blood levels of theophylline.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline.

Likelihood Possible Evidence D
Amoxicillin (Amoxil, Trimox)

Theoretically, black pepper might increase the effects and side effects of amoxicillin.
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin. This has not been reported in humans.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects. In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner.

Likelihood Possible Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.

Likelihood Possible Evidence D
Piperine full monograph & interactions

Milk Thistle extract17 drug types · 954 drugs

Antidiabetes Drugs

Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
Clinical research shows that milk thistle extract, alone or along with tree turmeric extract, can lower blood glucose levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, including those already taking antidiabetes drugs. Additionally, animal research shows that milk thistle extract increases the metformin maximum plasma concentration and area under the curve and decreases the renal clearance of metformin, due to inhibition of the multi-drug and toxin extrusion protein 1 (MATE1) renal tubular transport protein.

Likelihood Possible Evidence B
Cytochrome P450 2B6 (Cyp2B6) Substrates

Theoretically, milk thistle might inhibit CYP2B6.
An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels.

Likelihood Possible Evidence D
Glucuronidated Drugs

Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase, although the significance of this effect is unclear.

Likelihood Possible Evidence D
Ledipasvir

Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination.

Likelihood Possible Evidence D
Morphine

Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.
Animal research shows that milk thistle reduces serum levels of morphine by up to 66%. In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.

Likelihood Possible Evidence D
Raloxifene (Evista)

Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.
Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines.

Likelihood Possible Evidence D
Sirolimus (Rapamune)

Milk thistle might decrease the clearance of sirolimus.
Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients. It is unclear if this interaction occurs in patients without hepatic impairment.

Likelihood Possible Evidence B
Sofosbuvir (Solvaldi)

Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.
Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion. Whether this interaction occurs in humans is not known.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, milk thistle might increase the effects of warfarin.
In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement. Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
In vitro research suggests that milk thistle might inhibit CYP2C9. Additionally, 3 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP2C9 substrates, including imatinib and capecitabine. However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide. Differences in results could be due to differences in dosages or formulations utilized.

Likelihood Unlikely Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
While laboratory research shows conflicting results, pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir. However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine.

Likelihood Unlikely Evidence D
Estrogens

Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
Animal research suggests that a milk thistle extract of silymarin binds to estrogen receptor beta.

Likelihood Possible Evidence D
Hmg-Coa Reductase Inhibitors ("Statins")

Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).
Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action, and animal research shows this increases the maximum plasma concentration of pitavastatin and pravastatin. The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin.

Likelihood Unlikely Evidence D
Indinavir (Crixivan)

Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.
One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25%. However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir. Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir.

Likelihood Unlikely Evidence B
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Milk thistle may inhibit one form of OATP, OATP-B1, which could reduce the bioavailability and clinical effects of OATP-B1 substrates.
In vitro research shows that milk thistle inhibits OATP-B1. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are OATP substrates, including sorafenib and methotrexate. OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
In vitro research shows that milk thistle can inhibit P-glycoprotein activity and 1 case report from the World Health Organization (WHO) adverse drug reaction database describes increased abdominal pain in a patient taking milk thistle and the cancer medication vincristine, a P-glycoprotein substrate, though this patient was also taking methotrexate. However, a small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein substrate.

Likelihood Unlikely Evidence B
Milk Thistle extract full monograph & interactions

Bacopa extract8 drug types · 930 drugs

Anticholinergic Drugs

Theoretically, concurrent use might decrease the effectiveness of both agents.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs. Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.

Likelihood Possible Evidence D
Cevimeline (Evoxac)

Theoretically, bacopa might increase the effects and adverse effects of cevimeline.
In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes. However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels. Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.

Likelihood Possible Evidence D
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

Likelihood Possible Evidence D
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.
In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes. It is not known whether this is clinically significant.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.
Research on the effect of bacopa extracts on CYP2C9 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C9, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.
Research on the effects of bacopa extracts on CYP3A4 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and competitively inhibit CYP3A4, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, bacopa might have additive effects when used with thyroid hormone.
Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40%.

Likelihood Possible Evidence D
Bacopa extract full monograph & interactions

Grape seed extract9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water. Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

Likelihood Possible Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.

Likelihood Possible Evidence B
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination.

Likelihood Possible Evidence D
Phenacetin

Grape juice might decrease phenacetin absorption.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2).

Likelihood Possible Evidence B
Cytochrome P450 2C9 (Cyp2C9) Substrates

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.

Likelihood Unlikely Evidence D
Grape seed extract full monograph & interactions

Passionflower extract3 drug types · 836 drugs

Cns Depressants

Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.
Research in animals and humans shows that passion flower has sedative effects which can be additive when used with sedative medications like lorazepam.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, passion flower might decrease the effects of CYP3A4 substrates.
In vitro research suggests that passion flower can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer.

Likelihood Possible Evidence D
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Theoretically, passion flower might reduce the bioavailability of OATP2B1 and OATP1A2 substrates.
In vitro research shows that the passion flower constituents apigenin and vitexin inhibit OATP2B1 and OATP1A2. This inhibition may be dose-dependent. One specific high-flavonoid passion flower extract (Valverde) seems to inhibit OATP2B1 and OATP1A2, while another extract with a lower flavonoid concentration (Arkocaps) shows less potent inhibition. OATPs are responsible for the uptake of drugs and other compounds into the body; however, the specific activities of OATP2B1 and OATP1A2 are not well characterized.

Likelihood Possible Evidence D
Passionflower extract full monograph & interactions

Schisandra extract12 drug types · 803 drugs

Cyclophosphamide

Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.
In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively.

Likelihood Probable Evidence D
Cyclosporine (Neoral, Sandimmune)

Schisandra can increase the levels and clinical effects of cyclosporine.
A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations.

Likelihood Probable Evidence B
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.
In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate. Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.

Likelihood Probable Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.
In vitro and animal research suggests that schisandra induces CYP2C9 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.
Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol. Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism, this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.

Likelihood Probable Evidence D
Midazolam (Versed)

Schisandra can increase the levels and clinical effects of midazolam.
A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.
In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines. Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate. Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.

Likelihood Possible Evidence D
Sirolimus (Rapamune)

Schisandra can increase the levels and clinical effects of sirolimus.
A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

Schisandra can increase the levels and clinical effects of tacrolimus.
Clinical research in healthy children and adults, transplant patients, and patients with nephrotic syndrome and various rheumatic immunologic disorders shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, prolongs or delays time to peak tacrolimus concentrations, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 19% to 73%. This effect is thought to be due to inhibition of P-glycoprotein drug transporter and CYP3A4 and CYP3A5 by schisandra. Some clinical and observational studies suggest that schisandra increases tacrolimus levels similarly in both expressors and non-expressors of CYP3A5, while other studies suggest it does so to a greater degree in CYP3A5 expressors than non-expressors. Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus, and clinical and observational research in humans suggests that schisandra may increase whole blood levels of tacrolimus and decrease clearance of tacrolimus in a dose-dependent manner.

Likelihood Probable Evidence B
Talinolol

Schisandra can increase the levels and clinical effects of talinolol.
A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra. tly.

Likelihood Probable Evidence B
Voriconazole (Vfend)

Theoretically, schisandra might increase the levels and clinical effects of voriconazole.
Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, schisandra might decrease the levels and clinical effects of warfarin.
Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Schisandra extract full monograph & interactions

Vitamin E8 drug types · 764 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of alkylating agents.
There's concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Concomitant use of vitamin E and anticoagulant or antiplatelet agents might increase the risk of bleeding.
Vitamin E seems to inhibit of platelet aggregation and antagonize the effects of vitamin K-dependent clotting factors. These effects appear to be dose-dependent, and are probably only likely to be clinically significant with doses of at least 800 units daily. Mixed tocopherols, such as those found in food, might have a greater antiplatelet effect than alpha-tocopherol. RRR alpha-tocopherol (natural vitamin E) 1000 IU daily antagonizes vitamin K-dependent clotting factors. Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.

Likelihood Possible Evidence B
Antitumor Antibiotics

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of antitumor antibiotics.
There's concern that antioxidants could reduce the activity of antitumor antibiotic drugs such as doxorubicin, which generate free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

A specific form of vitamin E might increase absorption and levels of cyclosporine.
There is some evidence that one specific formulation of vitamin E (D-alpha-tocopheryl-polyethylene glycol-1000 succinate, TPGS, tocophersolan, Liqui-E) might increase absorption of cyclosporine. This vitamin E formulation forms micelles which seems to increase absorption of cyclosporine by 40% to 72% in some patients. However, this interaction is unlikely to occur with the usual forms of vitamin E.

Likelihood Unlikely Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.
Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4. Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.

Likelihood Possible Evidence D
Selumetinib (Koselugo)

Taking selumetinib with vitamin E can result in a total daily dose of vitamin E that exceeds safe limits and therefore might increase the risk of bleeding.
Selumetinib contains 48-54 IU vitamin E per capsule. The increased risk of bleeding with vitamin E appears to be dose-dependent. Be cautious when using selumetinib in combination with supplemental vitamin E, especially in patients at higher risk of bleed, such as those with chronic conditions and those taking antiplatelet drugs.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Using vitamin E with warfarin might increase the risk of bleeding.
Due to interference with production of vitamin K-dependent clotting factors, use of more than 400 IU of vitamin E daily with warfarin might increase prothrombin time (PT), INR, and the risk of bleeding,. At a dose of 1000 IU per day, vitamin E can antagonize vitamin K-dependent clotting factors even in people not taking warfarin. Limited clinical evidence suggests that doses up to 1200 IU daily may be used safely by patients taking warfarin, but this may not be applicable in all patient populations.

Likelihood Possible Evidence B
Niacin

Vitamin E might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises high-density lipoprotein (HDL) cholesterol levels in people with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50%. Vitamin E alone combined with a statin does not seem to decrease HDL levels. It is not known whether the adverse effect on HDL is due to one of the other antioxidants or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Vitamin E full monograph & interactions

Niacin15 drug types · 727 drugs

Alcohol (Ethanol)

Concomitant use of alcohol and niacin might increase the risk of flushing and hepatotoxicity.
Alcohol can exacerbate the flushing and pruritus associated with niacin. Large doses of niacin might also exacerbate liver dysfunction associated with chronic alcohol use. A case report describes delirium and lactic acidosis in a patient taking niacin 3 grams daily who ingested 1 liter of wine. Advise patients to avoid large amounts of alcohol while taking niacin.

Likelihood Probable Evidence D
Allopurinol (Zyloprim)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as allopurinol.
Large doses of niacin can reduce urinary excretion of uric acid, potentially resulting in hyperuricemia. Doses of uricosurics such as allopurinol might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Anticoagulant/Antiplatelet Drugs

Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.
Several cases of clotting factor synthesis deficiency and coagulopathy have been reported in patients taking sustained-release niacin. Also, thrombocytopenia has been reported in patients treated with niacin or niacin plus lovastatin.

Likelihood Possible Evidence D
Antidiabetes Drugs

Niacin can increase blood glucose levels and may diminish the effects of antidiabetes drugs.
Niacin impairs glucose tolerance in a dose-dependent manner, probably by causing or aggravating insulin resistance and increasing hepatic production of glucose. In diabetes patients, niacin 4.5 grams daily for 5 weeks can increase plasma glucose by an average of 16% and glycated hemoglobin (HbA1c) by 21%. However, lower doses of 1.5 grams daily or less appear to have minimal effects on blood glucose. In some patients, glucose levels increase when niacin is started, but then return to baseline when a stable dose is reached. Up to 35% of patients with diabetes may need adjustments in hypoglycemic therapy when niacin is added.

Likelihood Probable Evidence B
Antihypertensive Drugs

Theoretically, niacin may increase the risk of hypotension when used with antihypertensive drugs.
The vasodilating effects of niacin can cause hypotension. Furthermore, some clinical evidence suggests that a one-hour infusion of niacin can reduce systolic, diastolic, and mean blood pressure in hypertensive patients. This effect is not observed in normotensive patients.

Likelihood Possible Evidence B
Bile Acid Sequestrants

Bile acid sequestrants can bind niacin and decrease absorption. Separate administration by 4-6 hours to avoid an interaction.
In vitro studies show that colestipol (Colestid) binds about 98% of available niacin and cholestyramine (Questran) binds 10% to 30%.

Likelihood Possible Evidence D
Gemfibrozil (Lopid)

Theoretically, concomitant use of niacin and gemfibrozil might increase the risk of myopathy in some patients.
A case of myopathy from concomitant use of niacin and gemfibrozil has been reported. Niacin alone has also been associated with cases of myopathy. Using gemfibrozil with niacin might further increase the risk of developing myopathy.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.
Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses. Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin.

Likelihood Possible Evidence D
Hmg-Coa Reductase Inhibitors ("Statins")

Theoretically, concomitant use of niacin and statins might increase the risk of myopathy and rhabdomyolysis in some patients.
Some case reports have raised concerns that niacin might increase the risk of myopathy and rhabdomyolysis when combined with statins. However, a significantly increased risk of myopathy has not been demonstrated in clinical trials, including those using an FDA-approved combination of lovastatin and niacin (Advicor).

Likelihood Possible Evidence D
Probenecid (Benemid)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as probenecid.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as probenecid might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Sulfinpyrazone (Anturane)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as sulfinpyrazone.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as sulfinpyrazone might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Thyroid Hormone

Theoretically, niacin might antagonize the therapeutic effects of thyroid hormones.
Clinical research and case reports suggests that taking niacin can reduce serum levels of thyroxine-binding globulin by up to 25% and moderately reduce levels of thyroxine (T4). Patients taking thyroid hormone for hypothyroidism might need dose adjustments when using niacin.

Likelihood Probable Evidence D
Transdermal Nicotine (Nicoderm)

Theoretically, concomitant use of niacin and transdermal nicotine might increase the risk of flushing and dizziness.
Niacin and nicotine can both cause flushing and dizziness.

Likelihood Possible Evidence D
Warfarin (Coumadin)

There is limited evidence that niacin may increase the anticoagulant effects of warfarin.
In a case report, a patient on warfarin developed an elevated international normalized ratio (INR) of 3.9 after taking niacin for two weeks. The patient's INR was previously stable, ranging between 2 and 3 in recent months, and no other medication changes were identified. The elevated INR returned to therapeutic range within 4 days following the discontinuation of niacin.

Likelihood Possible Evidence D
Aspirin

Large doses of aspirin might alter the clearance of niacin.
Aspirin is often used with niacin to reduce niacin-induced flushing. Doses of 80-975 mg aspirin have been used, but 325 mg appears to be optimal. Aspirin also seems to reduce the clearance of niacin by competing for glycine conjugation. Taking aspirin 1 gram seems to reduce niacin clearance by 45%. This is probably a dose-related effect and not clinically significant with the more common aspirin dose of 325 mg.

Likelihood Likely Evidence B
Niacin full monograph & interactions

Gotu kola extract2 drug types · 579 drugs

Cns Depressants

Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.
In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.
There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases.

Likelihood Possible Evidence D
Gotu kola extract full monograph & interactions

Lithium11 drug types · 515 drugs

Diuretic Drugs

Theoretically, taking lithium supplements with loop diuretics might increase lithium levels and adverse effects.
Thiazide diuretics and loop diuretics might reduce lithium excretion, particularly in sodium-restricted patients. If lithium is clinically indicated and other treatment options are unavailable or inadequate in patients using diuretics, lithium treatment can be initiated with extreme caution. Serum lithium should be measured frequently and the doses used should be the lowest dose ordinarily tolerated. It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.

Likelihood Probable Evidence D
Serotonergic Drugs

Theoretically, taking lithium supplements with serotonergic drugs might both mask and increase the risk of serotonin syndrome.
In a case report, a 67-year-old female with depression and bipolar disorder using lithium in combination with selective serotonin reuptake inhibitors (SSRIs) and other medications developed serotonin syndrome with symptoms of deep tendon hyperreflexia, muscle rigidity, tremor, and hyperthermia. However, agitation, one classical symptom of serotonin syndrome, was lacking. This was thought to be due to masking by lithium toxicity. Lithium can increase serotonin levels, thus, combining serotonergic drugs with lithium might increase the risk of serotonergic side effects including serotonin syndrome and cerebral vasoconstrictive disorders. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.

Likelihood Probable Evidence D
Ace Inhibitors (Aceis)

Theoretically, taking lithium supplements with ACEIs might increase levels and adverse effects of lithium.
Concomitant administration of ACEIs with lithium may increase lithium concentrations. It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.

Likelihood Possible Evidence D
Anticonvulsants

Theoretically, taking lithium supplements with anticonvulsants might increase the risk of neurotoxicity.
Drugs such as carbamazepine and phenytoin seem to increase the risk of neurotoxicity. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.

Likelihood Possible Evidence D
Antipsychotic Drugs

Theoretically, taking lithium supplements with antipsychotic drugs might increase the risk of encephalopathic syndrome.
Encephalopathic syndrome has been reported in multiple patients taking prescription lithium and antipsychotics concomitantly. Symptoms have included weakness and lethargy, fever, confusion, and extrapyramidal symptoms. In some patients, resulting brain damage was irreversible. Although there is no established causal relationship between these symptoms and the combination of lithium and antipsychotic medications, there is a theoretical relationship. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.

Likelihood Possible Evidence D
Calcium Channel Blockers

Theoretically, taking lithium supplements with calcium channel blockers might reduce lithium levels and might also increase the risk of certain adverse effects.
Calcium channel blockers might reduce lithium concentrations. Monitor lithium levels with concurrent use. Calcium channel blockers might also increase the adverse neurological and gastrointestinal adverse effects of lithium. It is unclear if these interactions would occur with the smaller doses found in lithium supplements.

Likelihood Possible Evidence D
Methyldopa (Aldomet)

Theoretically, taking lithium supplements with methyldopa might increase the risk of lithium toxicity.
Concurrent use of methyldopa with lithium increases the risk of lithium toxicity. It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.

Likelihood Probable Evidence D
Methylxanthines

Theoretically, taking lithium supplements with methylxanthines might decrease lithium levels.
Xanthines such as aminophylline, caffeine, and theophylline (Theo-Dur, Theo-24, others) might increase the clearance of lithium. It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.

Likelihood Probable Evidence D
Nonsteroidal Anti-Inflammatory Drugs (Nsaids)

Theoretically, taking lithium supplements with NSAIDs might increase lithium levels and adverse effects.
NSAIDs can decrease the renal clearance of lithium and increase lithium levels. It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.

Likelihood Probable Evidence D
Phenothiazines

Theoretically, taking lithium supplements with phenothiazines might decrease the levels and clinical effects of phenothiazines.
Concomitant use of lithium with phenothiazines might reduce lithium concentrations. Lithium might also reduce phenothiazine concentrations, making the pharmacokinetic effect unpredictable. It is unclear if these interactions would occur with the smaller doses found in lithium supplements.

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

Theoretically, taking lithium supplements with skeletal muscle relaxants might prolong neuromuscular blockade.
Lithium might prolong neuromuscular blockade. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.

Likelihood Probable Evidence D
Lithium full monograph & interactions

5-HTP3 drug types · 398 drugs

Carbidopa (Lodosyn)

Combining 5-HTP and carbidopa can increase the risk of serotonergic side effects.
Carbidopa is sometimes used with 5-HTP to minimize peripheral 5-HTP metabolism and boost the amount that reaches the brain. However, this combination might also increase the risk of some side effects including hypomania, restlessness, rapid speech, anxiety, insomnia, and aggressiveness. Combining carbidopa and 5-HTP might also increase the risk of scleroderma-like skin changes due to elevated serotonin levels.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, concomitant use of 5-HTP with medications that cause sedation might have additive effects.
In clinical trials, 5-HTP has been associated with drowsiness and somnolence.

Likelihood Possible Evidence D
Serotonergic Drugs

Combining serotonergic drugs with 5-HTP might cause additive serotonergic effects.
5-HTP can increase serotonin levels and cause serotonergic effects. Theoretically, combining serotonergic drugs with 5-HTP might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders. However, serotonin syndrome with 5-HTP has not yet been reported in humans. Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using 5-HTP with serotonergic drugs.

Likelihood Possible Evidence D
5-HTP full monograph & interactions

Selenium6 drug types · 321 drugs

Anticoagulant/Antiplatelet Drugs

Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity. Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation.

Likelihood Possible Evidence D
Barbiturates

Theoretically, selenium might prolong the sedating effects of barbiturates.
Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates. Selenium seems to prolong the sedative effect of pentobarbital in animal models.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, selenium might interfere with warfarin activity.
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors. Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity.

Likelihood Possible Evidence D
Contraceptive Drugs

Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels. It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium.

Likelihood Possible Evidence B
Niacin

Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Selenium full monograph & interactions

Bilberry extract4 drug types · 275 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, bilberry fruit extract might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro, animal, and clinical research suggest that anthocyanidin extracts from bilberry can inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, bilberry leaf or fruit extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research suggests that bilberry leaf extract might have blood glucose-lowering activity. Also, one small clinical trial in patients with type 2 diabetes shows that taking bilberry fruit extract 470 mg as a single dose prior to an oral glucose tolerance test lowers plasma glucose levels when compared with placebo.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Theoretically, bilberry fruit extract might decrease levels of drugs metabolized by CYP2E1.
Animal research shows that exposure to small concentrations of bilberry extract in drinking water for around one month increased CYP2E1 activity by 31%. However, exposure over a 2-month period did not increase CYP2E1 activity. This effect has not been reported in humans.

Likelihood Possible Evidence D
Erlotinib (Tarceva)

Theoretically, bilberry fruit extract might reduce the efficacy of erlotinib.
In vitro research suggests that bilberry fruit extract and its constituents, delphinidin and delphinidin-3-O-glucoside, inhibit the activity of erlotinib. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Bilberry extract full monograph & interactions

Alpha Lipoic Acid5 drug types · 263 drugs

Alkylating Agents

Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of alkylating agents.
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy. Advise patients to consult their oncologist before using alpha-lipoic acid.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, alpha-lipoic acid may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro, alpha-lipoic acid inhibits platelet aggregation.

Likelihood Possible Evidence D
Antitumor Antibiotics

Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of antitumor antibiotics.
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of antitumor antibiotic drugs, which work by generating free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using alpha-lipoic acid.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, alpha-lipoic acid might decrease the effects of thyroid hormone drugs.
Animal research suggests that co-administration of thyroxine with alpha-lipoic acid reduces conversion into the active T3 form.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking alpha-lipoic acid with antidiabetes drugs might increase the risk of hypoglycemia.
Although some small clinical studies have suggested that alpha-lipoic acid can lower blood glucose levels, larger clinical studies in patients with diabetes have shown no clinically meaningful effect. Additionally, co-administration of single doses of alpha-lipoic acid and glyburide or acarbose did not cause detectable drug interactions in healthy volunteers.

Likelihood Unlikely Evidence B
Alpha Lipoic Acid full monograph & interactions

Huperzine A2 drug types · 219 drugs

Anticholinergic Drugs

Theoretically, huperzine A might decrease the effects of anticholinergic drugs.
Huperzine A has acetylcholinesterase (AChE) inhibiting effects. In animal models, huperzine A reversed cognitive deficits induced by scopolamine, an anticholinergic drug.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, concurrent use of huperzine A with cholinergic drugs might increase the effects and side effects of these medications.
Huperzine A can inhibit acetylcholinesterase (AChE) and might cause cumulative effects if used with cholinergic drugs.

Likelihood Possible Evidence B
Huperzine A full monograph & interactions

Phosphatidyl serine2 drug types · 219 drugs

Anticholinergic Drugs

Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.
Phosphatidylserine is thought to increase acetylcholine levels, which could theoretically interfere with the activity of anticholinergic agents.

Likelihood Possible Evidence B
Cholinergic Drugs

Theoretically, phosphatidylserine might have additive effects with cholinergic drugs.
Phosphatidylserine is thought to increase acetylcholine levels, which could theoretically lead to additive cholinergic effects when used with cholinergic drugs.

Likelihood Possible Evidence B
Phosphatidyl serine full monograph & interactions

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Levodopa

Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.

Likelihood Unlikely Evidence D
Vitamin B6 full monograph & interactions

Vinpocetine3 drug types · 208 drugs

Anticoagulant/Antiplatelet Drugs

Vinpocetine might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Clinical research shows that vinpocetine decreases red blood cell aggregation, as well as plasma and whole blood viscosity. This effect has been seen with intravenous vinpocetine 1 mg/kg and oral vinpocetine 30 mg daily. Vinpocetine also seems to have antiplatelet effects.

Likelihood Possible Evidence B
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, vinpocetine might increase levels of drugs metabolized by CYP2C9.
In vitro research shows that vinpocetine weakly inhibits CYP2C9. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Vinpocetine might modestly increase the risk of bleeding when taken with warfarin.
Clinical research shows that the combination of warfarin and vinpocetine leads to slight increases in prothrombin time and the area under the concentration curve for warfarin. However, these increases were small, and researchers suggest that this interaction is not likely to be clinically significant in most patients.

Likelihood Possible Evidence B
Vinpocetine full monograph & interactions

Acetyl L-Carnitine4 drug types · 203 drugs

Acenocoumarol (Sintrom)

Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.
L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is similar to warfarin, but shorter-acting. There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product. It is unclear if such an interaction would also occur with acetyl-L-carnitine.

Likelihood Possible Evidence D
Serotonergic Drugs

Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.
Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.
L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells. Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism. It is unclear if such an interaction would occur with acetyl-L-carnitine.

Likelihood Probable Evidence B
Warfarin (Coumadin)

Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin.
L-carnitine, the parent compound of acetyl-L-carnitine, might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin. There is not enough information to know whether this interaction occurs with acetyl-L-carnitine and warfarin.

Likelihood Possible Evidence D
Acetyl L-Carnitine full monograph & interactions

Hawthorn extract6 drug types · 191 drugs

Nitrates

Theoretically, concomitant use might cause additive coronary vasodilatory effects.
Some evidence shows that hawthorn might lower blood pressure due to vasodilatory effects.

Likelihood Probable Evidence D
Phosphodiesterase-5 Inhibitors

Theoretically, concomitant use might result in additive vasodilation and hypotension.
Hawthorn might inhibit PDE-5 and cause vasodilation.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, hawthorn may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that hawthorn can inhibit platelet aggregation. However, its effect in humans is unclear. One observational study shows that patients taking hawthorn shortly before undergoing coronary artery bypass graft (CABG) surgery or valve replacement surgery have a 10% incidence of postoperative bleeding, compared with 1% in those who never consumed hawthorn extract. However, clinical research shows that taking a specific preparation of dried hawthorn leaves and flowers (Crataesor, Soria Natural Lab) 800 mg three times daily for 15 days does not affect platelet aggregation or levels of thromboxane B2, the metabolite of thromboxane A2, in healthy humans.

Likelihood Possible Evidence D
Beta-Blockers

Theoretically, concomitant use might cause additive effects on blood pressure and heart rate.
Some evidence shows that hawthorn might lower blood pressure and heart rate.

Likelihood Possible Evidence D
Calcium Channel Blockers

Theoretically, concomitant use might cause additive coronary vasodilation and hypotensive effects.
Some evidence shows that hawthorn might lower blood pressure due to vasodilatory effects.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Theoretically, hawthorn might potentiate the effects and adverse effects of digoxin.
Hawthorn appears to improve cardiac output; however, hawthorn does not appear to affect digoxin pharmacokinetics. Case reports suggest that at least one species of hawthorn root extract (Crataegus mexicana) may produce adverse effects similar to digoxin and can cross-react with digoxin assays, leading to falsely elevated plasma digoxin levels.

Likelihood Possible Evidence D
Hawthorn extract full monograph & interactions

SAMe2 drug types · 189 drugs

Levodopa

SAMe might reduce the effectiveness of levodopa.
SAMe methylates levodopa, which might reduce its effectiveness for treating Parkinson disease.

Likelihood Possible Evidence D
Serotonergic Drugs

Taking SAMe with serotonergic drugs might increase the risk of serotonin syndrome and other serotonergic side effects.
SAMe has serotonergic effects. Theoretically, combining serotonergic drugs with SAMe might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders. In one case report, SAMe 100 mg intramuscularly was given daily with clomipramine (Anafranil) 25 mg per day. When the clomipramine dose was increased to 75 mg per day the patient experienced serotonin syndrome about 48-72 hours later, requiring hospitalization.

Likelihood Possible Evidence D
SAMe full monograph & interactions

Chromium5 drug types · 178 drugs

Antidiabetes Drugs

Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
Some research shows that taking chromium might lower blood glucose levels, especially in patients with poorly controlled type 2 diabetes.

Likelihood Possible Evidence A
Insulin

Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
In clinical research, chromium has been shown to increase insulin sensitivity,

Likelihood Possible Evidence B
Levothyroxine (Synthroid, Others)

Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone. Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.

Likelihood Probable Evidence B
Aspirin

Theoretically, aspirin might increase chromium absorption.
Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood.

Likelihood Possible Evidence D
Nonsteroidal Anti-Inflammatory Drugs (Nsaids)

NSAIDs might increase chromium levels in the body.
Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention.

Likelihood Possible Evidence D
Chromium full monograph & interactions

Lycopene1 drug type · 122 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, taking lycopene with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
In vitro research shows that lycopene has antiplatelet effects.

Likelihood Possible Evidence D
Lycopene full monograph & interactions

Inositol1 drug type · 86 drugs

Antidiabetes Drugs

Theoretically, taking inositol with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research shows that inositol lowers blood glucose levels and glycated hemoglobin (HbA1c) levels in patients with diabetes.

Likelihood Possible Evidence A
Inositol full monograph & interactions

Manganese3 drug types · 83 drugs

Antipsychotic Drugs

Theoretically, the risk for manganese toxicity might increase when taken with antipsychotic drugs.
Hallucinations and behavioral changes have been reported in a patient with liver disease who was taking haloperidol and manganese. Researchers speculate that taking manganese along with haloperidol, phenothiazine-derivatives, or other antipsychotic medications might increase the risk of manganese toxicity in some patients.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, manganese might reduce the absorption of quinolone antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced quinolone absorption have been reported between quinolones and other multivalent cations, such as calcium and iron.

Likelihood Probable Evidence D
Tetracycline Antibiotics

Theoretically, manganese might reduce the absorption of tetracycline antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced tetracycline absorption have been reported between tetracyclines and other multivalent cations, such as calcium and iron.

Likelihood Probable Evidence D
Manganese full monograph & interactions

Zinc10 drug types · 67 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Theoretically, zinc might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after zinc containing products.

Likelihood Probable Evidence D
Cephalexin (Keflex)

Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.
A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose. To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.

Likelihood Probable Evidence B
Cisplatin (Platinol-Aq)

Theoretically, zinc might interfere with the therapeutic effects of cisplatin.
Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin. It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.

Likelihood Possible Evidence D
Integrase Inhibitors

Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Zinc is a divalent cation. Pharmacokinetic studies have shown that other divalent cations such as calcium and iron can decrease blood levels of the integrase inhibitor dolutegravir through chelation.

Likelihood Possible Evidence D
Penicillamine (Cuprimine, Depen)

Zinc might reduce the levels and clinical effects of penicillamine.
By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated. Advise patients to take zinc and penicillamine at least 2 hours apart.

Likelihood Probable Evidence B
Quinolone Antibiotics

Zinc can decrease the levels and clinical effects of quinolones antibiotics.
Quinolones form complexes with zinc in the gastrointestinal tract, reducing absorption of both the quinolone and zinc if taken at the same time. Advise patients to take these drugs at least 2 hours before, or 4-6 hours after, zinc supplements.

Likelihood Probable Evidence B
Ritonavir (Norvir)

Zinc modestly reduces levels of ritonavir.
Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption. In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16%. However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Zinc might reduce levels of tetracycline antibiotics.
Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time. Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40%. Demeclocycline and minocycline cause a similar interaction. However, doxycycline does not seem to interact significantly with zinc. Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.

Likelihood Probable Evidence B
Amiloride (Midamor)

Amiloride can modestly reduce zinc excretion and increase zinc levels.
Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses. The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.

Likelihood Probable Evidence B
Atazanavir (Reyataz)

Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.
Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption. Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication.

Likelihood Probable Evidence B
Zinc full monograph & interactions

L-Glutamine1 drug type · 50 drugs

Anticonvulsants

Theoretically, glutamine might antagonize the effects of anticonvulsant medications.
Glutamine is metabolized to the excitatory neurotransmitter glutamate. Glutamate might have antagonistic effects with anticonvulsant drugs. However, this interaction has not yet been reported in humans.

Likelihood Possible Evidence D
L-Glutamine full monograph & interactions

Folic Acid7 drug types · 40 drugs

5-Fluorouracil

Theoretically, high doses of folic acid might increase the toxicity of 5-fluorouracil.
Increases in gastrointestinal side effects of 5-fluorouracil, such as stomatitis and diarrhea, have been described in two clinical studies when leucovorin, a form of folic acid, was administered with 5-fluorouracil.

Likelihood Possible Evidence D
Capecitabine (Xeloda)

Use of high-dose folic acid might contribute to capecitabine toxicity.
Clinical research suggests that higher serum folate levels are associated with an increased risk for moderate or severe toxicity during capecitabine-based treatment for colorectal cancer. Additionally, in one case report, taking folic acid 15 mg daily might have contributed to increased toxicity, including severe diarrhea, vomiting, edema, hand-foot syndrome, and eventually death, in a patient prescribed capecitabine.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Folic acid might reduce the efficacy of methotrexate as a cancer treatment when given concurrently.
Methotrexate exerts its cytotoxic effects by preventing conversion of folic acid to the active form needed by cells. There is some evidence that folic acid supplements reduce the efficacy of methotrexate in the treatment of acute lymphoblastic leukemia, and theoretically they could reduce its efficacy in the treatment of other cancers. Advise cancer patients to consult their oncologist before using folic acid supplements. In patients treated with long-term, low-dose methotrexate for rheumatoid arthritis (RA) or psoriasis, folic acid supplements can reduce the incidence of side effects, without reducing efficacy.

Likelihood Probable Evidence B
Phenobarbital (Luminal)

Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of phenobarbital and worsening seizure control. Monitor closely for increased seizure activity.

Likelihood Probable Evidence B
Phenytoin (Dilantin)

Folic acid might reduce serum levels of phenytoin in some patients.
Folic acid may be a cofactor in phenytoin metabolism. Folic acid, in doses of 1 mg daily or more, can reduce serum levels of phenytoin in some patients. Increases in seizure frequency have been reported. If folic acid supplements are added to established phenytoin therapy, monitor serum phenytoin levels closely. If phenytoin and folic acid are started at the same time and continued together, adverse changes in phenytoin pharmacokinetics are avoided. Note that phenytoin also reduces serum folate levels.

Likelihood Probable Evidence B
Primidone (Mysoline)

Folic acid might have antagonistic effects on primidone and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of primidone and worsening seizure control. Monitor closely for increased seizure activity. Note that primidone also reduces serum folate levels.

Likelihood Probable Evidence B
Pyrimethamine (Daraprim)

Folic acid might antagonize the effects of pyrimethamine.
Folic acid can antagonize the antiparasitic effects of pyrimethamine against toxoplasmosis and Pneumocystis carinii pneumonia. Folic acid doesn't antagonize the effects of pyrimethamine in the treatment of malaria, because malarial parasites cannot use exogenous folic acid. Use folinic acid as an alternative to folic acid when indicated.

Likelihood Probable Evidence D
Folic Acid full monograph & interactions

Betain HCL3 drug types · 36 drugs

Antacids

Betaine hydrochloride increases stomach acidity and could decrease the effects of antacids.
In human research, betaine hydrochloride increases stomach acidity. Antacids are taken to decrease stomach acidity. Theoretically, taking betaine hydrochloride along with antacids might decrease the effects of the antacids.

Likelihood Possible Evidence D
H2-Blockers

Betaine hydrochloride increases stomach acidity and could decrease the effects of H2-blockers.
In human research, betaine hydrochloride increases stomach acidity. H2-blockers are used to decrease stomach acidity. Theoretically, taking betaine hydrochloride along with H2-blockers might decrease the effects of H2-blockers.

Likelihood Possible Evidence D
Proton Pump Inhibitors (Ppis)

Betaine hydrochloride increases stomach acidity and could decrease the effects of PPIs.
In human research, betaine hydrochloride increases stomach acidity. PPIs are used to decrease stomach acidity. Theoretically, taking betaine hydrochloride along with PPIs might decrease the effects of PPIs

Likelihood Possible Evidence D
Betain HCL full monograph & interactions

Copper2 drug types · 31 drugs

Penicillamine (Cuprimine, Depen)

Theoretically, taking copper with penicillamine might decrease the absorption of penicillamine; separate dosing by at least 2 hours.
Copper chelates penicillamine, which decreases its absorption and may reduce its clinical effects.

Likelihood Probable Evidence D
Contraceptive Drugs

Theoretically, taking copper with contraceptive drugs might increase the levels and toxic effects of copper.
A meta-analysis of clinical studies suggests that chronic use of oral contraceptives increases serum copper levels by a mean of 57 mcg/dL. In most people, this resulted in levels above the normal reference range for copper.

Likelihood Possible Evidence D
Copper full monograph & interactions

L-Tyrosine2 drug types · 21 drugs

Levodopa

Theoretically, tyrosine might decrease the effectiveness of levodopa.
Tyrosine and levodopa compete for absorption in the proximal duodenum by the large neutral amino acid (LNAA) transport system. Advise patients to separate doses of tyrosine and levodopa by at least 2 hours.

Likelihood Probable Evidence D
Thyroid Hormone

Theoretically, tyrosine might have additive effects with thyroid hormone medications.
Tyrosine is a precursor to thyroxine and might increase levels of thyroid hormones.

Likelihood Probable Evidence D
L-Tyrosine full monograph & interactions

Riboflavin1 drug type · 20 drugs

Tetracycline Antibiotics

Theoretically, taking riboflavin with tetracycline antibiotics may decrease the potency of these antibiotics.
In vitro research suggests that riboflavin may inhibit the potency of tetracycline antibiotics. It is not clear if this effect is clinically significant, as this interaction has not been reported in humans.

Likelihood Possible Evidence D
Riboflavin full monograph & interactions

Choline Bitartrate1 drug type · 16 drugs

Atropine

Theoretically, choline might decrease the effects of atropine in the brain.
Animal research shows that administering choline one hour before administering atropine can attenuate atropine-induced decreases in brain levels of acetylcholine. Theoretically, concomitant use of choline and atropine may decrease the effects of atropine.

Likelihood Possible Evidence D
Choline Bitartrate full monograph & interactions

Thiamine1 drug type · 3 drugs

Trimethoprim (Proloprim)

Trimethoprim might increase blood levels of thiamine.
In vitro, animal, and clinical research suggest that trimethoprim inhibits intestinal thiamine transporter ThTR-2, hepatic transporter OCT1, and renal transporters OCT2, MATE1, and MATE2, resulting in paradoxically increased thiamine plasma concentrations.

Likelihood Probable Evidence B
Thiamine full monograph & interactions

L-Lysine Hydrochloride1 drug type · 1 drug

5-Ht4 Agonists

Theoretically, lysine may reduce the effects of 5-HT4 agonists.
Animal research suggests that L-lysine is a partial serotonin receptor 4 (5-HT4) antagonist and inhibits diarrhea induced by the 5-HT4 agonist, 5-hydroxytryptophane.

Likelihood Unlikely Evidence D
L-Lysine Hydrochloride full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Neuro-Natural Recall, from the product label.

XtendLife

Web Address
www.xtend-life.com
Pharmacist Counseling Corner

Neuro-Natural Recall by XtendLife: Common Questions

Does Neuro-Natural Recall by XtendLife interact with any medications?
Yes. Based on its ingredients, Neuro-Natural Recall has a known interaction with 1,918 medications, including 285 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Neuro-Natural Recall contains 48 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Not sure if Neuro-Natural Recall is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Neuro-Natural Recall label
Go deeper

The Full Monographs Behind Neuro-Natural Recall’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Glutamine

Interacts with 50 drugs

Glutamine is the most abundant amino acid in the body and is usually made in your muscles. A prescription form is FDA-approved to help reduce sickle cell disease complications, but for most...

Read the full Glutamine monograph → Herb & supplement monograph

Folic Acid

Interacts with 40 drugs

Folic acid is the man-made form of vitamin B9 and is one of the most well-studied supplements, especially for preventing serious birth defects when taken before and during early pregnancy. I...

Read the full Folic Acid monograph → Herb & supplement monograph

Pantothenic Acid

Pantothenic acid is vitamin B5, an essential nutrient your body uses to turn food into energy. True deficiency is very rare because it is found in nearly all foods, and most people meet thei...

Read the full Pantothenic Acid monograph → Herb & supplement monograph

Thiamine

Interacts with 3 drugs

Thiamine (vitamin B1) is an essential nutrient your body needs to turn food into energy and to keep your nerves and heart healthy. Most people get enough from food, but supplements are clear...

Read the full Thiamine monograph → Herb & supplement monograph

Biotin

Biotin (vitamin B7) is a water-soluble vitamin your body needs to turn food into energy and to support healthy hair, skin, and nails. Most people get plenty from a normal diet, and true defi...

Read the full Biotin monograph → Herb & supplement monograph

Methionine

Methionine is an essential amino acid that your body needs for protein building and many basic chemical reactions. Most people get enough from a normal diet, and supplements are generally no...

Read the full Methionine monograph → Herb & supplement monograph

Lysine

Interacts with 1 drug

Lysine is an essential amino acid your body cannot make on its own, so it must come from food or supplements. People most often take extra lysine to try to prevent or shorten cold sores, but...

Read the full Lysine monograph → Herb & supplement monograph

Tyrosine

Interacts with 21 drugs

L-tyrosine is an amino acid your body uses to make brain chemicals like dopamine and norepinephrine. Some studies suggest it may help mental performance during short-term stress, sleep loss,...

Read the full Tyrosine monograph → Herb & supplement monograph

Inositol

Interacts with 86 drugs

Inositol is a sugar alcohol made naturally in the body and found in many foods, and it is sold as a supplement (often myo-inositol) mainly for PCOS, mood, and metabolic concerns. The stronge...

Read the full Inositol monograph → Herb & supplement monograph

Boron

Boron is a trace mineral found in many plant foods and sold as a supplement, mainly promoted for bone, joint, and hormone health. The human evidence for most of these uses is limited or prel...

Read the full Boron monograph → Herb & supplement monograph

Vitamin E

Interacts with 764 drugs

Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correct a true deficiency, but high-dose vitam...

Read the full Vitamin E monograph → Herb & supplement monograph

Choline

Interacts with 16 drugs

Choline is an essential nutrient your body needs for liver function, brain health, and nerve signaling, and many people get enough from foods like eggs, meat, and fish. Supplements may help...

Read the full Choline monograph → Herb & supplement monograph

Zinc

Interacts with 67 drugs

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but supplements can help correct or prevent a defici...

Read the full Zinc monograph → Herb & supplement monograph

Selenium

Interacts with 321 drugs

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who eat a varied diet get enough, and supple...

Read the full Selenium monograph → Herb & supplement monograph

5-htp

Interacts with 398 drugs

5-HTP is a compound your body uses to make serotonin, and people take it as a supplement hoping to improve mood, sleep, and headaches. Some early research is promising, but the overall evide...

Read the full 5-htp monograph → Herb & supplement monograph

Ginkgo

Interacts with 1,266 drugs

Ginkgo is one of the world's most popular herbal supplements, mostly taken to support memory and circulation. The evidence for these uses is mixed and generally weak, and it is not proven to...

Read the full Ginkgo monograph → Herb & supplement monograph

Green Tea

Interacts with 1,293 drugs

Green tea is a popular beverage rich in antioxidants called catechins, and drinking it in normal amounts is considered safe for most people. Concentrated green tea extracts are a different s...

Read the full Green Tea monograph → Herb & supplement monograph

Acetyl-l-carnitine

Interacts with 203 drugs

Acetyl-L-carnitine is a form of the amino acid carnitine that the body uses to help produce energy in cells. It is most studied for nerve pain and memory-related conditions, though the evide...

Read the full Acetyl-l-carnitine monograph → Herb & supplement monograph

Alpha-lipoic Acid

Interacts with 263 drugs

Alpha-lipoic acid (ALA) is an antioxidant made naturally by the body and found in small amounts in foods. It is most studied for diabetic nerve pain, where some evidence suggests it may help...

Read the full Alpha-lipoic Acid monograph → Herb & supplement monograph

Riboflavin

Interacts with 20 drugs

Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally very safe at typical doses, and the stro...

Read the full Riboflavin monograph → Herb & supplement monograph

Passion Flower

Interacts with 836 drugs

Passion flower is a traditional calming herb that many people use for anxiety and sleep. Early studies hint it may help with mild anxiety and restlessness, but the evidence is limited and mo...

Read the full Passion Flower monograph → Herb & supplement monograph

Eleuthero

Interacts with 1,140 drugs

Eleuthero is an herb traditionally used as an 'adaptogen' to fight fatigue, boost energy, and help the body handle stress. The scientific evidence behind these uses is limited and mixed, so...

Read the full Eleuthero monograph → Herb & supplement monograph

Grape

Interacts with 910 drugs

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is he...

Read the full Grape monograph → Herb & supplement monograph

Schisandra

Interacts with 803 drugs

Schisandra is a traditional Chinese medicine berry used as an adaptogen for stress, fatigue, and liver support. Human evidence is limited and most claims are not well proven, but it appears...

Read the full Schisandra monograph → Herb & supplement monograph

Molybdenum

Molybdenum is an essential trace mineral your body needs in tiny amounts to help certain enzymes work. Most people get enough from a normal diet, so supplements are rarely needed unless a do...

Read the full Molybdenum monograph → Herb & supplement monograph

Niacin

Interacts with 727 drugs

Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescription-strength niacin has been used to...

Read the full Niacin monograph → Herb & supplement monograph

Chromium

Interacts with 178 drugs

Chromium is an essential trace mineral involved in how the body handles sugar and fat. Some studies suggest it may modestly help blood sugar control in certain people with type 2 diabetes, b...

Read the full Chromium monograph → Herb & supplement monograph

Lycopene

Interacts with 122 drugs

Lycopene is a red plant pigment and antioxidant found mainly in tomatoes and other red fruits. Eating lycopene-rich foods is linked with possible heart and prostate benefits, but evidence fr...

Read the full Lycopene monograph → Herb & supplement monograph

Copper

Interacts with 31 drugs

Copper is an essential trace mineral your body needs in small amounts for making red blood cells, supporting nerves and bones, and helping enzymes work. Most people get enough copper from fo...

Read the full Copper monograph → Herb & supplement monograph

Manganese

Interacts with 83 drugs

Manganese is an essential trace mineral your body needs in small amounts for bone formation, metabolism, and antioxidant defense, and most people get enough from a normal diet. Supplements m...

Read the full Manganese monograph → Herb & supplement monograph

Same

Interacts with 189 drugs

SAM-e is a compound your body makes naturally that is sold as a supplement, most often for depression and osteoarthritis. Some research suggests it may help with these conditions, but the qu...

Read the full Same monograph → Herb & supplement monograph

Black Pepper

Interacts with 1,019 drugs

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (li...

Read the full Black Pepper monograph → Herb & supplement monograph

Bilberry

Interacts with 275 drugs

Bilberry is a blueberry-like fruit rich in antioxidant plant compounds called anthocyanins, and it has a long history of traditional use for eye health, circulation, and mild diarrhea. While...

Read the full Bilberry monograph → Herb & supplement monograph

Lecithin

Lecithin is a natural fatty substance found in foods and made by the body that is widely used as a supplement and food emulsifier. Evidence supporting most of its health claims is limited, t...

Read the full Lecithin monograph → Herb & supplement monograph

Betaine Hydrochloride

Interacts with 36 drugs

Betaine hydrochloride is a supplement used to temporarily increase stomach acid in people who may have low acid levels. Evidence for its benefits is limited and mostly based on tradition rat...

Read the full Betaine Hydrochloride monograph → Herb & supplement monograph

Milk Thistle

Interacts with 954 drugs

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin. While it is generally well tolerated, th...

Read the full Milk Thistle monograph → Herb & supplement monograph

Hawthorn

Interacts with 191 drugs

Hawthorn is a plant traditionally used for heart-related complaints, and some studies suggest it may modestly help symptoms of mild heart failure when added to standard care. However, the ev...

Read the full Hawthorn monograph → Herb & supplement monograph

Quercetin

Interacts with 1,169 drugs

Quercetin is a plant flavonoid with antioxidant and anti-inflammatory properties found in many common foods and sold as a supplement. While early research is interesting for allergies, blood...

Read the full Quercetin monograph → Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-rel...

Read the full Vitamin B6 monograph → Herb & supplement monograph

Bacopa

Interacts with 930 drugs

Bacopa is an Ayurvedic herb most often used for memory and thinking. Some small studies suggest it may modestly help memory when taken regularly for several weeks, but the evidence is limite...

Read the full Bacopa monograph → Herb & supplement monograph

Huperzine A

Interacts with 219 drugs

Huperzine A is a purified compound from a Chinese clubmoss that acts like a mild cholinesterase inhibitor, similar in mechanism to some prescription Alzheimer's drugs. Some small studies sug...

Read the full Huperzine A monograph → Herb & supplement monograph

Lithium

Interacts with 515 drugs

Lithium is a naturally occurring metal that, in prescription form (lithium carbonate or citrate), is an FDA-approved, well-proven treatment for bipolar disorder. Low-dose supplement forms li...

Read the full Lithium monograph → Herb & supplement monograph

Gotu Kola

Interacts with 579 drugs

Gotu kola is a traditional Ayurvedic and Asian herb that people use for wound healing, circulation, skin problems, and as a calming or memory-supporting herb. Some early studies suggest poss...

Read the full Gotu Kola monograph → Herb & supplement monograph

Yucca

Yucca is a desert plant traditionally used for joint pain, arthritis, and digestion, and it contains compounds called saponins thought to have anti-inflammatory effects. Human evidence for t...

Read the full Yucca monograph → Herb & supplement monograph

Phosphatidylserine

Interacts with 219 drugs

Phosphatidylserine is a natural fat-like compound found in cell membranes, especially in the brain, and it is sold mainly to support memory and thinking. Some research suggests possible bene...

Read the full Phosphatidylserine monograph → Herb & supplement monograph

Vinpocetine

Interacts with 208 drugs

Vinpocetine is a lab-made compound based on a chemical from the periwinkle plant, and it is marketed mainly for memory and brain health. The evidence behind these uses is limited and not str...

Read the full Vinpocetine monograph →
Sources

Sources & How We Checked

Neuro-Natural Recall's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 1,374 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Glutamine 11 references
  1. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev 1999;4:239-48..
  2. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. Nutrition 1997;13:748-51.. PubMed
  3. Mebane AH. L-Glutamine and mania. Am J Psychiatry 984;141:1302-3.
  4. Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 2000;130:1007S-15S.. PubMed
  5. Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr 2001;131:2556S-61S.. PubMed
  6. Chapman AG. Glutamate and epilepsy. J Nutr 2000;130:1043S-5S.. PubMed
  7. Ziegler TR. Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. J Nutr 2001;131:2578S-84S.. PubMed
  8. Laviano A, Molfino A, Lacaria MT, Canelli A, De Leo S, Preziosa I, Rossi Fanelli F. Glutamine supplementation favors weight loss in nondieting obese female patients. A pilot study. Eur J Clin Nutr. 2014 Nov;68(11):1264-6. PubMed
  9. Endari (l-glutamine) [package insert]. Torrance, CA: Emmaus Medical,Inc; 2017.
  10. Niihara Y, Miller ST, Kanter J, et al. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med 2018;379(3):226-35. doi: 10.1056/NEJMoa1715971.
  11. Ogden HB, Child RB, Fallowfield JL, et al. Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study. Nutrients. 2020;12(10):2953. PubMed

See these in context on the Glutamine monograph →

Folic Acid 56 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol 1993;28:466-9. PubMed
  3. Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41. PubMed
  4. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed
  5. Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726-35. PubMed
  6. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-6. PubMed
  7. Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: Before and after folic acid administration. Epilepsia 1992;33:712-20. PubMed
  8. Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41:1125-9. PubMed
  9. Leeb BF, Witzmann G, Ogris E, et al. Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients. Clin Exp Rheumatol 1995;13:459-63.
  10. Morgan SL, Baggott JE, Lee JY, Alarcón GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease preventi
  11. Dijkmans BA. Folate supplementation and methotrexate. Br J Rheumatol 1995;34:1172-4. PubMed
  12. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  13. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed
  14. Amer College of Rheumatology ad hoc committee on clinical guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723-31. DOI
  15. Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc 2000;100:88-94. PubMed
  16. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  17. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-78.
  18. Antony AC. Megaloblastic Anemias. In: Hoffman R, Benz Jr EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone 2000: 451-79.
  19. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96. DOI
  20. Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.
  21. Ortiz Z, Shea B, Suarez Almazor M, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis (Cochrane Review). Cochrane Database Syst Rev 2000;2:CD000951. PubMed
  22. Van Delden C, Hirschel B. Folinic acid supplements to pyrimethamine-sulfadiazine for Toxoplasma encephalitis are associated with better outcome (letter). J Infect Dis 1996;173:1294-5. PubMed
  23. Schroder H, Clausen N, Ostergard E, Pressler T. Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia. Ped Hematol Oncol 1986;3:241-7. PubMed
  24. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673-81. PubMed
  25. Morris MC, Evans DA, Bienias JL, et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 2005;62:641-5. PubMed
  26. Bonaa KH, Njolstad I, Ueland PM, et al. NORVIT: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Enlg J Med 2006;354:1578-88. PubMed
  27. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64. PubMed
  28. Figueiredo JC, Grau MV, Haile RW, et al. Folic acid and risk of prostate cancer: Results from a randomized clinical trial. J Natl Cancer Inst 2009;101:432-5. PubMed
  29. Clippe C, Freyer G, Milano G, Trillet-Lenoir V. Lethal toxicity of capecitabine due to abusive folic acid prescription. Clin Oncol (R Coll Radiol) 2003;15:299-300. PubMed
  30. Bedford Laboratories. Leucovorin calcium [package insert]. Bedford, OH. September 2008. Available at: http://www.bedfordlabs.com/BedfordLabsWeb/products/inserts/LCV-P02.pdf.
  31. Ebbing M, Bonaa KH, Nygard O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009;302:2119-26.
  32. Haberg, S. E., London, S. J., Stigum, H., Nafstad, P., and Nystad, W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis.Child 2009;94(3):180-184. PubMed
  33. Whitrow, M. J., Moore, V. M., Rumbold, A. R., and Davies, M. J. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol. 12-15-2009;170(12):1486-1493. PubMed
  34. Collin, S. M., Metcalfe, C., Refsum, H., Lewis, S. J., Zuccolo, L., Smith, G. D., Chen, L., Harris, R., Davis, M., Marsden, G., Johnston, C., Lane, J. A., Ebbing, M., Bonaa, K. H., Nygard, O., Ueland, P. M., Grau, M. V., Baron, J. A., Donovan, J. L., Nea
  35. Baggott, J. E., Oster, R. A., and Tamura, T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol. 2012;36(1):78-81. PubMed
  36. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  37. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  38. Taneja S, Strand TA, Kumar T, et al. Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial. Am J Clin Nutr 2013;98(3):731-7. PubMed
  39. van Wijngaarden JP, Swart KM, Enneman AW, et al. Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial. Am J Clin
  40. Qin X, Fan F, Cui Y, Chen F, Chen Y, Cheng X, Li Y, Wang B, Xu X, Xu X, Huo Y, Wang X. Folic acid supplementation with and without vitamin B6 and revascularization risk: a meta-analysis of randomized controlled trials. Clin Nutr. 2014;33(4):603-12. PubMed
  41. Crider KS, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am J Clin Nutr. 2013;98(5):1272-81. PubMed
  42. Matsubara S, Imai K, Murayama K, Higashizawa T. Severe liver dysfunction during nausea and vomiting of pregnancy: folic acid supplement as a suggested culprit. J Obstet Gynaecol. 2012;32(7):701-2. PubMed
  43. Qin X, Cui Y, Shen L, Sun N, Zhang Y, Li J, Xu X, Wang B, Xu X, Huo Y, Wang X. Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials. Int J Cancer. 2013 1;133(5):1033-41. PubMed
  44. Tio M, Andrici J, Cox MR, Eslick GD. Folate intake and the risk of prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2014;17(3):213-9. PubMed
  45. Tomaszewski JJ, Richman EL, Sadetsky N, O'Keefe DS, Carroll PR, Davies BJ, Chan JM. Impact of folate intake on prostate cancer recurrence following definitive therapy: data from CaPSURE. J Urol. 2014;191(4):971-6. PubMed
  46. Valera-Gran D, García de la Hera M, Navarrete-Muñoz EM, Fernandez-Somoano A, Tardón A, Julvez J, Forns J, Lertxundi N, Ibarluzea JM, Murcia M, Rebagliato M, Vioque J; Infancia y Medio Ambiente (INMA) Project. Folic acid supplements during pregnancy and ch
  47. Van Der Woude DA, De Vries J, Van Wijk EM, Verzijl JM, Pijnenborg JM. A randomized controlled trial examining the addition of folic acid to iron supplementation in the treatment of postpartum anemia. Int J Gynaecol Obstet. 2014;126(2):101-5. PubMed
  48. Vila-Nova C, Wehby GL, Queirós FC, Chakraborty H, Félix TM, Goco N, Moore J, Gewehr EV, Lins L, Affonso CM, Murray JC. Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil. J Perinat Med. 201 PubMed
  49. Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J, Manson JE, Hankey GJ, Spence JD, Galan P, Bønaa KH, Jamison R, Gaziano JM, Guarino P, Baron JA, Logan RF, Giovannucci EL, den Heijer M, Ueland PM, Bennett D, Collins R, Peto R; B-V
  50. Wehby GL, Félix TM, Goco N, Richieri-Costa A, Chakraborty H, Souza J, Pereira R, Padovani C, Moretti-Ferreira D, Murray JC. High dosage folic acid supplementation, oral cleft recurrence and fetal growth. Int J Environ Res Public Health. 2013 4;10(2):590-6 PubMed
  51. Fanidi A, Carreras-Torres R, Larose TL, et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019 Sep 15;145(6):1499-1503. PubMed
  52. Liu J, Li Z, Ye R, Liu J, Ren A. Periconceptional folic acid supplementation and risk of parent-reported asthma in children at 4-6 years of age. ERJ Open Res. 2020;6(1):00250-2019. PubMed
  53. Houghton LA, Sherwood KL, Pawlosky R, Ito S, O'Connor DL. [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr. 2006 Apr;83(4):842-50. PubMed
  54. Houghton LA, Yang J, O'Connor DL. Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements. Am J Clin Nutr. 2009 Jan;89(1):216-20. PubMed
  55. Chan SL, Chan AWH, Mo F, et al. Association Between Serum Folate Level and Toxicity of Capecitabine During Treatment for Colorectal Cancer. Oncologist. 2018 Dec;23(12):1436-1445. PubMed
  56. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T

See these in context on the Folic Acid monograph →

Pantothenic Acid 11 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Debourdeau PM, Djezzar S, Estival JL, et al. Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H. Ann Pharmacother 2001;35:424-6. DOI
  4. Schmuth, M., Wimmer, M. A., Hofer, S., Sztankay, A., Weinlich, G., Linder, D. M., Elias, P. M., Fritsch, P. O., and Fritsch, E. Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double-blind study. Br.J.Dermatol. 2 PubMed
  5. Schreck, U., Paulsen, F., Bamberg, M., and Budach, W. Intraindividual comparison of two different skin care conceptions in patients undergoing radiotherapy of the head-and-neck region. Creme or powder? Strahlenther.Onkol. 2002;178(6):321-329. PubMed
  6. Herbst, R. A., Uter, W., Pirker, C., Geier, J., and Frosch, P. J. Allergic and non-allergic periorbital dermatitis: patch test results of the Information Network of the Departments of Dermatology during a 5-year period. Contact Dermatitis 2004;51(1):13-1 PubMed
  7. Champault, G. and Patel, J. C. [Treatment of constipation with Bepanthene]. Med.Chir Dig. 1977;6(1):57-59.
  8. Scott LN, Fiume M, Bergfeld WF, et al. Safety Assessment of Panthenol, Pantothenic Acid, and Derivatives as Used in Cosmetics. Int J Toxicol 2022;41(3_suppl):77-128. PubMed
  9. Han J, Warshaw EM. Allergic Contact Dermatitis to Panthenol in "Hypoallergenic" Products. Dermatitis 2023;34(1):62-63. PubMed
  10. Blanchard G, Kerre S, Walker A, et al. Allergic contact dermatitis from pantolactone and dexpanthenol in wound healing creams. Contact Dermatitis 2022;87(5):468-471. PubMed
  11. Peltier E, Trapp S, de Salvo R, et al. A new dexpanthenol-containing liquid cleanser for atopic-prone skin: Results from two prospective clinical studies evaluating cutaneous tolerability, moisturization potential, and effects on barrier function. J Cosme PubMed

See these in context on the Pantothenic Acid monograph →

Thiamine 7 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  4. Rogovik, A. L., Vohra, S., and Goldman, R. D. Safety considerations and potential interactions of vitamins: should vitamins be considered drugs? Ann.Pharmacother. 2010;44(2):311-324. PubMed
  5. Arruti N, Bernedo N, Audicana MT, Villarreal O, Uriel O, Muñoz D. Systemic allergic dermatitis caused by thiamine after iontophoresis. Contact Dermatitis. 2013 Dec;69(6):375-6. PubMed
  6. Thiamine hydrochloride injection package insert. Lake Zurich, IL: Fresenius Kabi, LLC; September 2019.
  7. Vora B, Wen A, Yee SW, et al. The Effect of Trimethoprim on Thiamine Absorption: A Transporter-Mediated Drug-Nutrient Interaction. Clin Pharmacol Ther 2023;114(2):381-392.

See these in context on the Thiamine monograph →

Biotin 4 references
  1. Debourdeau PM, Djezzar S, Estival JL, et al. Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H. Ann Pharmacother 2001;35:424-6. DOI
  2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  3. Mock DM, Quirk JG, Mock NI. Marginal biotin deficiency during normal pregnancy. Am J Clin Nutr 2002;75:295-9. PubMed
  4. Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study.Mult Scler Relat Disord. 2015;4(2):159-69. doi: 10.1016/j.msard.2015.01.005. PubMed

See these in context on the Biotin monograph →

Methionine 12 references
  1. La Vecchia C, Negri E, Franceschi S, Decarli A. Case-control study on influence of methionine, nitrite, and salt on gastric carcinogenesis in northern Italy. Nutr Cancer 1997;27:65-8. PubMed
  2. Btaiche IF, Khalidi N. Parenteral nutrition-associated liver complications in children. Pharmacotherapy 2002;22:188-211.. PubMed
  3. Cottington EM, LaMantia C, Stabler SP, et al. Adverse event associated with methionine loading test: a case report. Arterioscler Thromb Vasc Biol 2002;22:1046-50.. PubMed
  4. Anon. Should methionine be added to paracetamol formulations? Drug Ther Perspect 1997;10:11-3. DOI
  5. Smulders, Y. M., Rakic, M., Slaats, E. H., Treskes, M., Sijbrands, E. J., Odekerken, D. A., Stehouwer, C. D., and Silberbusch, J. Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and c
  6. McAuley, D. F., Hanratty, C. G., McGurk, C., Nugent, A. G., and Johnston, G. D. Effect of methionine supplementation on endothelial function, plasma homocysteine, and lipid peroxidation. J.Toxicol.Clin.Toxicol. 1999;37(4):435-440. PubMed
  7. Hanratty, C. G., McGrath, L. T., McAuley, D. F., Young, I. S., and Johnston, G. D. The effects of oral methionine and homocysteine on endothelial function. Heart 2001;85(3):326-330. PubMed
  8. Ward, M., McNulty, H., McPartlin, J., Strain, J. J., Weir, D. G., and Scott, J. M. Effect of supplemental methionine on plasma homocysteine concentrations in healthy men: a preliminary study. Int.J.Vitam.Nutr.Res. 2001;71(1):82-86. PubMed
  9. Yaghmai, R., Kashani, A. H., Geraghty, M. T., Okoh, J., Pomper, M., Tangerman, A., Wagner, C., Stabler, S. P., Allen, R. H., Mudd, S. H., and Braverman, N. Progressive cerebral edema associated with high methionine levels and betaine therapy in a patient
  10. Talukdar R, Murthy HV, Reddy DN. Role of methionine containing antioxidant combination in the management of pain in chronic pancreatitis: a systematic review and meta-analysis. Pancreatology 2015;15(2):136-44. PubMed
  11. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press, 2005. Available at: https://doi.org/10.17226 DOI
  12. Khairan P, Sobue T, Eshak ES, et al. Association of B Vitamins and Methionine Intake with the Risk of Gastric Cancer: The Japan Public Health Center-based Prospective Study. Cancer Prev Res (Phila) 2022;15(2):101-110. PubMed

See these in context on the Methionine monograph →

Lysine 7 references
  1. Thein DJ, Hurt WC. Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg Oral Med Oral Pathol 1984;58:659-66. PubMed
  2. McCune MA, Perry HO, Muller SA, O'Fallon WM. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis 1984;34:366-73.
  3. DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Arch Dermatol 1984;120:48-51. DOI
  4. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980;60:85-7.
  5. Griffith RS, Walsh DE, Myrmel KH, et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica 1987;175:183-90. DOI
  6. Lo JC, Chertow GM, Rennke H, Seifter JL. Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion. Am J Kidney Dis 1996;28:614-7. PubMed
  7. Smriga M, Torii K. L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15370-5.

See these in context on the Lysine monograph →

Tyrosine 4 references
  1. Meyer JS, Welch KM, Deshmukh VD, et al. Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease. J Amer Geriat Soc 1977;25:289-98.
  2. DiPiro JT, Talbert RL, Yee GC, et al; eds. Pharmacotherapy: A pathophysiologic approach. 4th ed. Stamford, CT: Appleton & Lange, 1999.
  3. Wood DR, Reimherr FW, Wender PH. Amino acid precursors for the treatment of attention deficit disorder, residual type. Psychopharmacol Bull 1985;21:146-9.
  4. van Spronsen FJ, van Rijn M, Bekhof J. Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets. Am J Clin Nutr 2001;73:153-7. PubMed

See these in context on the Tyrosine monograph →

Inositol 14 references
  1. Palatnik A, Frolov K, Fux M, Benjamin J. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. J Clin Psychopharmacol 2001;21:335-9.. PubMed
  2. Allan SJ, Kavanagh GM, Herd RM, Savin JA. The effect of inositol supplements on the psoriasis of patients taking lithium: a randomized, placebo-controlled trial. Br J Dermatol 2004;150:966-9. PubMed
  3. Machado-Vieira R, Viale CI, Kapczinski F. Mania associated with an energy drink: the possible role of caffeine, taurine, and inositol. Can J Psychiatry 2001;46:454-5. PubMed
  4. Kamenov Z, Kolarov G, Gateva A, Carlomagno G, Genazzani AD. Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol 2015;31(2):131-5. PubMed
  5. Matarrelli B, Vitacolonna E, D'Angelo M, et al. Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial. J Matern Fetal Neonatal Med 2013;26(1 PubMed
  6. Mukai T, Kishi T, Matsuda Y, Iwata N. A meta-analysis of inositol for depression and anxiety disorders. Hum Psychopharmacol 2014;29(1):55-63. PubMed
  7. Farren M, Daly N, McKeating A, Kinsley B, Turner MJ, Daly S. The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial. Diabetes Care. 2017;40(6):759-63. PubMed
  8. Zheng X, Liu Z, Zhang Y, et al. Relationship Between Myo-Inositol Supplementary and Gestational Diabetes Mellitus: A Meta-Analysis. Medicine (Baltimore). 2015;94(42):e1604. PubMed
  9. Crawford TJ, Crowther CA, Alsweiler J, Brown J. Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes. Cochrane Database Syst Rev. 2015;(12):CD011507. PubMed
  10. Maurizi AR, Menduni M, Del Toro R, et al. A pilot study of D-chiro-inositol plus folic acid in overweight patients with type 1 diabetes. Acta Diabetol. 2017;54(4):361-65. PubMed
  11. Leppink EW, Redden SA, Grant JE. A double-blind, placebo-controlled study of inositol in trichotillomania. Int Clin Psychopharmacol. 2017;32(2):107-14. PubMed
  12. Lam S, Mandrekar SJ, Gesthalter Y. A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia. Cancer Prev Res (Phila). 2016;9(12):906-14.
  13. Wozniak J, Faraone SV, Chan J, et al. A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study. J Clin Psychiatry. PubMed
  14. Vitale SG, Corrado F, Caruso S, et al. Myo-inositol supplementation to prevent gestational diabetes in overweight non-obese women: bioelectrical impedance analysis, metabolic aspects, obstetric and neonatal outcomes - a randomized and open-label, placebo-

See these in context on the Inositol monograph →

Boron 6 references
  1. Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
  2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  3. Thai L, Hart LL. Boric acid vaginal suppositories. Ann Pharmacother 1993;27:1355-7.
  4. Acs N, Banhidy F, Puho E, Czeizel AE. Teratogenic effects of vaginal boric acid treatment during pregnancy. Int J Gynaecol Obstet 2006;93:55-6. PubMed
  5. Garabrant, D. H., Bernstein, L., Peters, J. M., and Smith, T. J. Respiratory and eye irritation from boron oxide and boric acid dusts. J Occup Med 1984;26(8):584-586. PubMed
  6. Hjelm C, Harari F, Vahter M. Pre- and postnatal environmental boron exposure and infant growth: results from a mother-child cohort in northern Argentina. Environ Res 2019;171:60-8. PubMed

See these in context on the Boron monograph →

Vitamin E 64 references
  1. Kim JM, White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol 1996;77:545-6. PubMed
  2. Corrigan JJ Jr. The effect of vitamin E on warfarin-induced vitamin K deficiency. Ann N Y Acad Sci 1982;393:361-8. PubMed
  3. Corrigan JJ Jr. Coagulation problems relating to vitamin E. Am J Pediatr Hematol Oncol 1979;1:169-73.
  4. Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA 1974;230:1300-1. DOI
  5. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  6. Chang T, Benet LZ, Hebert MF. The effect of water-soluble vitamin E on cyclosporine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther 1996;59:297-303. PubMed
  7. Pan SH, Lopez RR Jr, Sher LS, et al. Enhanced oral cyclosporine absorption with water-soluble vitamin E early after liver transplantation. Pharmacother 1996;16:59-65. DOI
  8. Anon. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Soprawivenza nell'Infarto miocardico. Lancet 1999;354:447-55. DOI
  9. Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet 1999;354:810-6. DOI
  10. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N Engl J Med 2000;342:154-60. PubMed
  11. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study. Lancet 1996;347:781-6.
  12. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-35. PubMed
  13. Takahashi O. Haemorrhagic toxicity of a large dose of alpha-, beta-, gamma- and delta-tocopherols, ubiquinone, beta-carotene, retinol acetate and L-ascorbic acid in the rat. Food Chem Toxicol 1995;33:121-8.
  14. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  15. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med 1997;336:1216-22. PubMed
  16. Liede KE, Haukka JK, Saxen LM, Heinonen OP. Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid. Ann Med 1998;30:542-6.
  17. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  18. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  19. Liu M, Wallmon A, Olsson-Mortlock C, et al. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr 2003;77:700-6. PubMed
  20. Sokol RJ, Johnson KE, Karrer FM, et al. Improvement of cyclosporin absorption in children after liver transplantation by means of water-soluble vitamin E. Lancet 1991;338:212-4.. PubMed
  21. Stein JH, Carlsson CM, Papcke-Benson K, et al. The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia. J Am Coll Cardiol 2001;38:1806-13.. PubMed
  22. Carlsson CM, Papcke-Benson K, Carnes M, et al. Health-related quality of life and long-term therapy with pravastatin and tocopherol (vitamin E) in older adults. Drugs Aging 2002;19:793-805. . PubMed
  23. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  24. Schrogie JJ. Coagulopathy and fat-soluble vitamins (letter). JAMA 1975;232:19. DOI
  25. Celestini A, Pulcinelli FM, Pignatelli P, et al. Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets. Haematologica 2002;87:420-6.
  26. Stampfer MJ, Jakubowski JA, Faigel D, et al. Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels. Am J Clin Nutr 1988;47:700-6. PubMed
  27. Jandak J, Steiner M, Richardson PD. Alpha-tocopherol, an effective inhibitor of platelet adhesion. Blood 1989;73:141-9. DOI
  28. Freedman JE, Farhat JH, Loscalzo J, Keaney JF. Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. Circulation 1996;94:2434-40. PubMed
  29. Steiner M. Vitamin E, a modifier of platelet function: rationale and use in cardiovascular and cerebrovascular disease. Nutr Rev 1999;57:306-9. PubMed
  30. Brodkin RH, Bleiberg J. Sensitivity to topically applied vitamin E. Arch Dermatol 1965;92:76-7. DOI
  31. Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr 2004;80:143-8. PubMed
  32. Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:60520-53. PubMed
  33. Lonn E, Bosch J, Yusuf S, et al. HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293:1338-47. PubMed
  34. Landes N, Pfluger P, Kluth D, et al. Vitamin E activates gene expression via the pregnane X receptor. Biochem Pharmacol 2003;65:269-73. . PubMed
  35. Brigelius-Flohe R. Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305:737-40. PubMed
  36. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  37. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  38. Schurks M, Glynn RJ, Rist PM, et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomized controlled trials. BMJ 2010;341: c5702. doi: 10.1136/bmj.c5702.
  39. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64. PubMed
  40. Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate total cancer in men: the physicians' health study II randomised controlled trial. JAMA 2009;301:52-62.
  41. Hayden KM, Welsh-Bohmer KA, Wengreen HJ, et al; Cache County Investigators. Risk of mortality with vitamin E supplements: the Cache County study. Am L Med 2007;120:180-4. PubMed
  42. Smedts HP, de Vries JH, Rakhshandehroo M, et al. High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring. BJOG 2009;116:416-23. PubMed
  43. Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306:1549-56. PubMed
  44. Huang, H. Y., Caballero, B., Chang, S., Alberg, A. J., Semba, R. D., Schneyer, C. R., Wilson, R. F., Cheng, T. Y., Vassy, J., Prokopowicz, G., Barnes, G. J., and Bass, E. B. The efficacy and safety of multivitamin and mineral supplement use to prevent ca
  45. Sesso, H. D., Buring, J. E., Christen, W. G., Kurth, T., Belanger, C., MacFadyen, J., Bubes, V., Manson, J. E., Glynn, R. J., and Gaziano, J. M. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomiz
  46. Papaioannou, D., Cooper, K. L., Carroll, C., Hind, D., Squires, H., Tappenden, P., and Logan, R. F. Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis. Colorec PubMed
  47. Cooper, K., Squires, H., Carroll, C., Papaioannou, D., Booth, A., Logan, R. F., Maguire, C., Hind, D., and Tappenden, P. Chemoprevention of colorectal cancer: systematic review and economic evaluation. Health Technol.Assess. 2010;14(32):1-206. PubMed
  48. Mathew, M. C., Ervin, A. M., Tao, J., and Davis, R. M. Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract. Cochrane.Database.Syst.Rev. 2012;6:CD004567. PubMed
  49. Rahimi, R., Nikfar, S., Rezaie, A., and Abdollahi, M. A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens.Pregnancy. 2009;28(4):417-434. PubMed
  50. Soares, K. V. and McGrath, J. J. Vitamin E for neuroleptic-induced tardive dyskinesia. Cochrane.Database.Syst.Rev. 2001;(4):CD000209. DOI
  51. Roed-Petersen, J. and Hjorth, N. Contact dermatitis from antioxidants. Br.J.Dermatol. 1976;94(3):233-241. PubMed
  52. Brion, L. P., Bell, E. F., Raghuveer, T. S., and Soghier, L. What is the appropriate intravenous dose of vitamin E for very-low-birth-weight infants? J.Perinatol. 2004;24(4):205-207. PubMed
  53. Manny, T., Pettus, J., Hemal, A., Marks, M., and Mirzazadeh, M. Penile sclerosing lipogranulomas and disfigurement from use of "1Super Extenze" among Laotian immigrants. J.Sex Med. 2011;8(12):3505-3510. PubMed
  54. Musso, G., Cassader, M., Rosina, F., and Gambino, R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabe PubMed
  55. Bell, E. F. Upper limit of vitamin E in infant formulas. J.Nutr. 1989;119(12 Suppl):1829-1831. PubMed
  56. Manzano, D., Aguirre, A., Gardeazabal, J., Eizaguirre, X., and Diaz Perez, J. L. Allergic contact dermatitis from tocopheryl acetate (vitamin E) and retinol palmitate (vitamin A) in a moisturizing cream. Contact Dermatitis 1994;31(5):324.
  57. Barak, Y., Swartz, M., Shamir, E., Stein, D., and Weizman, A. Vitamin E (alpha-tocopherol) in the treatment of tardive dyskinesia: a statistical meta-analysis. Ann.Clin.Psychiatry 1998;10(3):101-105.
  58. Chae CU, Albert CM, Moorthy MV, et al. Vitamin E supplementation and the risk of heart failure in women. Circ Heart Fail. 2012;5(2):176-82. PubMed
  59. Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA. Vitamin E supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004069. PubMed
  60. Prescribing information: KOSELUGO (selumetinib) capsules. U.S. Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf.
  61. Warshaw EM, Ruggiero JL, DeKoven JG, et al. Patch testing with tocopherol and tocopherol acetate: the North American Contact Dermatitis Group experience, 2001 to 2016. Dermatitis. 2021;32(5):308-18. PubMed
  62. US Preventive Services Task Force, Mangione CM, Barry MJ, et al. Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2022;327(23):2326-2333. PubMed
  63. Abrol R, Kaushik R, Goel D, Sama S, Kaushik RM, Kala M. Vitamin E-induced coagulopathy in a young patient: a case report. J Med Case Rep 2023;17(1):107. PubMed
  64. Abtahi-Naeini B, Rastegarnasab F, Saffaei A. Liquid vitamin E injection for cosmetic facial rejuvenation: A disaster report of lipogranuloma. J Cosmet Dermatol 2022;21(11):5549-5554. PubMed

See these in context on the Vitamin E monograph →

Choline 14 references
  1. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  2. Cho E, Willett WC, Colditz GA, et al. Dietary choline and betaine and the risk of distal colorectal adenoma in women. J Natl Cancer Inst 2007;99:1224-31. PubMed
  3. Schmidt, C., Abicht, A., Krampfl, K., Voss, W., Stucka, R., Mildner, G., Petrova, S., Schara, U., Mortier, W., Bufler, J., Huebner, A., and Lochmuller, H. Congenital myasthenic syndrome due to a novel missense mutation in the gene encoding choline acetyl
  4. Tamminga, C., Smith, R. C., Chang, S., Haraszti, J. S., and Davis, J. M. Depression associated with oral choline. Lancet 10-23-1976;2(7991):905. PubMed
  5. Wood, J. L. and Allison, R. G. Effects of consumption of choline and lecithin on neurological and cardiovascular systems. Fed.Proc. 1982;41(14):3015-3021.
  6. Growdon, J. H. and Gelenberg, A. J. Choline and lecithin administration to patients with tardive dyskinesia. Trans.Am.Neurol.Assoc. 1978;103:95-99.
  7. Smith, C. M., Swash, M., Exton-Smith, A. N., Phillips, M. J., Overstall, P. W., Piper, M. E., and Bailey, M. R. Choline therapy in Alzheimer's disease. Lancet 8-5-1978;2(8084):318. PubMed
  8. Morrison, L. M. and W. F. Gonzales. Choline in coronary atherosclerosis. Amer.Heart J. 1950;39:729.
  9. Christie, J. G. Blackburn 1. M. Glen A. I. M. Zeisel S. Shering A. & Yates C. M. Effects of choline and lecithin on CSF choline levels and on cognitive functioning in patients with presenile dementia of the Alzheimer type. Nutrition and the brain 1979;5
  10. Sidhu N, Davies S, Nadarajah A, et al. Oral choline supplementation for postoperative pain. Br J Anaesth 2013;111(2):249-55. PubMed
  11. Wozniak JR, Fuglestad AJ, Eckerle JK, et al. Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability. Nutr Res. 2013;33(11):897-904. PubMed
  12. Wozniak JR, Fuglestad AJ, Eckerle JK, et al. Choline supplementation in children with fetal alcohol disorders: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2015;102(5): 1113-25.
  13. Ross RG, Hunter SK, McCarthy L, et al. Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. Am J Psychiatry. 2013;170(3):290-8. PubMed
  14. Food and Nutrition Board, Institute of Medicine. Choline. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:390-422.

See these in context on the Choline monograph →

Zinc 88 references
  1. Barceloux DG. Zinc. J Toxicol Clin Toxicol 1999;37:279-92.
  2. Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984;25:20-4. DOI
  3. Smith DS, Helzner EC, Nuttall CE Jr, et al. Failure of zinc gluconate in treatment of acute upper respiratory tract infections. Antimicrob Agents Chemother 1989;33:646-8. PubMed
  4. Blondeau JM. Expanded activity and utility of the new fluoroquinolones: a review. Clin Ther 1999;21:3-40. PubMed
  5. Reyes AJ, Olhaberry JV, Leary WP, et al. Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J 1983;64:936-41.
  6. Kugelmas M. Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 2000;19:13-5. PubMed
  7. Hebel SK, ed. Drug Facts and Comparisons. 52nd ed. St. Louis: Facts and Comparisons, 1998.
  8. Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med 1998;18:673-85. DOI
  9. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, et al. Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. PubMed
  10. Fosmire GJ. Zinc toxicity. Am J Clin Nutr 1990;51:225-7.
  11. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. PubMed
  12. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  13. Seelig MS. Auto-immune complications of D-penicillamine - A possible result of zinc and magnesium depletion and of pyridoxine inactivation. J Am Coll Nutr 1982;1:207-14. PubMed
  14. Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs 1976;11:45-54.. PubMed
  15. Hirt M, Nobel S, Barron E. Zinc nasal gel for the treatment of common cold symptoms: A double-blind, placebo-controlled trial. Ear Nose Throat J 2000;79:778-82.. DOI
  16. Simkin PA. Oral zinc sulphate in rheumatoid arthritis. Lancet 1976;2:539-42. PubMed
  17. Wray D. A double-blind trial of systemic zinc sulfate in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982;53:469-72. PubMed
  18. Douglas RM, Miles HB, Moore BW, et al. Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract infections in Australian adults. Antimicrob Agents Chemother 1987;31:1263-5. PubMed
  19. Lagiou P, Wuu J, Trichopoulou A, et al. Diet and benign prostatic hyperplasia: a study in Greece. Urology 1999;54:284-90. PubMed
  20. Ewing CI, Gibbs AC, Ashcroft C, David TJ. Failure of oral zinc supplementation in atopic eczema. Eur J Clin Nutr 1991;45:507-10.
  21. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  22. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. AREDS report no. 8. Arch Oph
  23. Greenberg JE, Lynn M, Kirsner RS, et al. Mucocutaneous pigmented macule as a result of zinc deposition. J Cutan Pathol 2002;29:613-5. PubMed
  24. Godfrey HR, Godfrey NJ, Godfrey JC, Riley D. A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med 2001;7:49-56.
  25. Turner RB. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis 2001;33:1865-70. PubMed
  26. Belongia EA, Berg R, Liu K. A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults. Am J Med 2001;111:103-8. PubMed
  27. Mossad SB. Effect of zincum gluconicum nasal gel on the duration and symptom severity of the common cold in otherwise healthy adults. QJM 2003;96:35-43. DOI
  28. Leitzmann MF, Stampfer MJ, Wu K, et al. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst 2003;95:1004-7.. PubMed
  29. Jafek BW, Linschoten M, Murrow BW. Zicam Induced Anosmia. American Rhinologic Society 49th Annual Fall Scientific Meeting abstract. Orlando, Florida. September 20, 2003. http://app.american-rhinologic.org/programs/2003ARSFallProgram071503.pdf (Accessed 24
  30. Uebayashi H, Hatanaka T, Kanemura F, Tonosaki K. Acute anosmia in the mouse: behavioral discrimination among the four basic taste substances. Physiol Behav 2001;72:291-6.. PubMed
  31. Barrett S. Zicam Marketers Sued. United States District Court Western District of Michigan Southern Division, Filed October 14, 2003, Case No. 4:03CV0146.
  32. Bilici M, Yildirim F, Kandil S, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:181-90.. PubMed
  33. Polk RE, Healy DP, Sahai J, et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother 1989;33:1841-4. PubMed
  34. Mery C, Delrieu F, Ghozlan R, et al. Controlled trial of D-penicillamine in rheumatoid arthritis. Dose effect and the role of zinc. Scand J Rheumatol 1976;5:241-7. PubMed
  35. Penttila O, Hurme H, Neuvonen PJ. Effect of zinc sulfate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4.
  36. Kondo Y, Yamagata K, Satoh M, et al. Optimal administration schedule of cisplatin for bladder tumor with minimal induction of metallothionein. J Urol 2003;170:2467-70. PubMed
  37. Doz F, Berens ME, Deschepper CF, et al. Experimental basis for increasing the therapeutic index of cis-diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high-zinc diet. Cancer Chemother Pharmacol 1992;29:219-26.
  38. Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12. PubMed
  39. Golik A, Modai D, Weissgarten J, et al. Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion. Clin Pharmacol Ther 1987;42:42-4. PubMed
  40. Leary WP, Reyes AJ, Van der Byl K. Urinary magnesium and zinc excretion after two different single doses of amiloride in healthy adults. Curr Ther Res 1983;34:205-16.
  41. McBride K, Slotnick B, Margolis FL. Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study. Chem Senses 2003;28:659-70. PubMed
  42. Burd GD. Morphological study of the effects of intranasal zinc sulfate irrigation on the mouse olfactory epithelium and olfactory bulb. Microsc Res Tech 1993;24:195-213. PubMed
  43. Ducray A, Bondier JR, Michel G, et al. Recovery following peripheral destruction of olfactory neurons in young and adult mice. Eur J Neurosci 2002;15:1907-17. PubMed
  44. Mayer AD, Rosenblatt JS. Peripheral olfactory deafferentation of the primary olfactory system in rats using ZnSO4 nasal spray with special reference to maternal behavior. Physiol Behav 1993;53:587-92. PubMed
  45. DeCook CA, Hirsch AR. Anosmia due to inhalational zinc: a case report (abstract). Chem Senses 2000;25:659.
  46. Tisdall FF, Brown A, Defries RD. Persistent anosmia following zinc sulfate nasal spraying. JPed 1938;18:60-2. DOI
  47. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64. PubMed
  48. Public Health Advisory. Loss of sense of smell with intranasal cold remedies containing zinc. U.S. Food and Drug Administration, June 16, 2009. Available at: http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm166059.htm (Accessed 16 June 2009)
  49. Dooren JC. FDA warns against use of Zicam. The Wall Street Journal, June 16, 2009. Available at: http://online.wsj.com/article/SB124516778692319231.html#mod=djemHL?mg=com-wsj (Accessed 16 June 2009).
  50. Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced anosmia syndrome. Laryngoscope 2006;116:217-20.
  51. Health Canada / GlaxoSmithKline Consumer Healthcare. Association of long-term, excessive use of zinc-containing Poli-Grip products with myeloneuropathy and blood dyscrasias. February 18, 2010. Available at: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medef
  52. GlaxoSmithKline Consumer Advisory. GlaxoSmithKline (GSK) warns about a potential health risk associated with long-term, excessive use of GSK's zinc-containing denture adhesives Super Polygrip Original, Ultra Fresh and Extra Care. February 18, 2010. Availa
  53. Science M, Johnstone J, Roth DE, et al. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 2012;184:E551-61. PubMed
  54. Castilla-Higuero, L., Romero-Gomez, M., Suarez, E., and Castro, M. Acute hepatitis after starting zinc therapy in a patient with presymptomatic Wilson's disease. Hepatology 2000;32(4 Pt 1):877. PubMed
  55. Sharquie, K. E., Najim, R. A., Farjou, I. B., and Al Timimi, D. J. Oral zinc sulphate in the treatment of acute cutaneous leishmaniasis. Clin.Exp.Dermatol. 2001;26(1):21-26. PubMed
  56. Dreno, B., Moyse, D., Alirezai, M., Amblard, P., Auffret, N., Beylot, C., Bodokh, I., Chivot, M., Daniel, F., Humbert, P., Meynadier, J., and Poli, F. Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of
  57. Moore, R. Bleeding gastric erosion after oral zinc sulphate. Br.Med J 3-25-1978;1(6115):754. PubMed
  58. Jafek, B. W., Linschoten, M. R., and Murrow, B. W. Anosmia after intranasal zinc gluconate use. Am J Rhinol. 2004;18(3):137-141. DOI
  59. Simonart, T. and de, Maertelaer, V. Systemic treatments for cutaneous warts: a systematic review. J Dermatolog.Treat. 2012;23(1):72-77. PubMed
  60. Cochran, R. J., Tucker, S. B., and Flannigan, S. A. Topical zinc therapy for acne vulgaris. Int.J Dermatol. 1985;24(3):188-190. DOI
  61. Morgan, A. A. Bleeding gastric erosion after oral zinc sulphate. Br.Med.J. 5-13-1978;1(6122):1283-1284. PubMed
  62. Murphy, J. V. Intoxication following ingestion of elemental zinc. JAMA 6-22-1970;212(12):2119-2120.
  63. Lang, C. J., Rabas-Kolominsky, P., Engelhardt, A., Kobras, G., and Konig, H. J. Fatal deterioration of Wilson's disease after institution of oral zinc therapy. Arch Neurol. 1993;50(10):1007-1008. PubMed
  64. Fjellner, B. Drug-induced lupus erythematosus aggravated by oral zinc therapy. Acta Derm.Venereol. 1979;59(4):368-370. DOI
  65. Varas Lorenzo, M. J. Zinc acexamate and ranitidine in the short- and mid-term management of gastroduodenal ulcers. Curr Ther Res 21986;39:19-29.
  66. Bosch, F. and Jimenez, E. Post-marketing surveillance of zinc acexamate in peptic ulcer treatment. Clin Trials J 1990;27:301-312.
  67. DeCook, C. A. and Hirsch, A. R. Anosmia due to inhalational zinc: a case report (abstract). Chem Senses 2000;25:659.
  68. Crown LA, May JA. Zinc toxicity: denture adhesives, bone marrow failure and polyneuropathy. Tenn Med. 2012 Feb;105(2):39-40, 42.
  69. Dadamio J, Van Tournout M, Teughels W, Dekeyser C, Coucke W, Quirynen M. Efficacy of different mouthrinse formulations in reducing oral malodour: a randomized clinical trial. J Clin Periodontol. 2013 May;40(5):505-13. PubMed
  70. Moyle G, Else L, Jackson A, Back D, Yapa MH, Seymour N, Ringner-Nackter L, Karolia Z, Gazzard B, Boffito M. Coadministration of atazanavir-ritonavir and zinc sulfate: impact on hyperbilirubinemia and pharmacokinetics. Antimicrob Agents Chemother. 2013 Aug PubMed
  71. Zittel S, Ufer F, Gerloff C, Münchau A, Rosenkranz M. Severe myelopathy after denture cream use--is copper deficiency or excess zinc the cause? Clin Neurol Neurosurg. 2014 Jun;121:17-8. PubMed
  72. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  73. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Drug Interactions between Integrase Inhibitors and Other Drugs. AIDSinfo. July 14, 2016. Available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescen
  74. Ding Y, Jia YY, Li F, et al. The effect of staggered administration of zinc sulfate on the pharmacokinetics of oral cephalexin. Br J Clin Pharmacol. 2012 Mar;73(3):422-7. PubMed
  75. Fallah R, Sabbaghzadegan S, Karbasi SA, Binesh F. Efficacy of zinc sulfate supplement on febrile seizure recurrence prevention in children with normal serum zinc level: A randomised clinical trial. Nutrition. 2015;31(11-12):1358-61. PubMed
  76. Lazzerini M, Wanzira H. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2016;12:CD005436. PubMed
  77. Mahmoud AM, Al-Alem U, Dabbous F, et al. Zinc intake and risk of prostate cancer: Case-control study and meta-analysis. PLoS One. 2016;11(11):e0165956. PubMed
  78. Nagraj SK, George RP, Shetty N, Levenson D, Ferraiolo DM, Shrestha A. Interventions for managing taste disturbances. Cochrane Database Syst Rev. 2017 Dec 20;12(12):CD010470. PubMed
  79. Yee BE, Richards P, Sui JY, Marsch AF. Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatol Ther. 2020:e14252. PubMed
  80. Janyajirawong R, Vilaichone RK, Sethasine S. Efficacy of zinc supplement in minimal hepatic encephalopathy: A prospective, randomized controlled study (Zinc-MHE Trial). Asian Pac J Cancer Prev 2021;22(9):2879-2887. PubMed
  81. Nakano M, Nakamura Y, Miyazaki A, Takahashi J. Zinc pharmacotherapy for elderly osteoporotic patients with zinc deficiency in a clinical setting. Nutrients 2021;13(6):1814. PubMed
  82. Tolino E, Skroza N, Mambrin A, et al. An open-label study comparing oral zinc to lymecycline in the treatment of acne vulgaris. J Clin Aesthet Dermatol 2021;14(5):56-58.
  83. Hunter J, Arentz S, Goldenberg J, et al. Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2021;11(11):e047474. PubMed
  84. Yamazaki K, Kageyama H, Fujiyama T, Ito T, Urano S, Honda T. A case of systemic contact dermatitis due to zinc supplements. Int J Dermatol 2022. PubMed
  85. Magham K, Han J, Eilbert W, Bunney EB. Severe copper deficiency anemia caused by zinc supplement use. Am J Emerg Med 2023;72:222. PubMed
  86. Sivakumar RR, Chinnaiah Govindareddy D, Sahoo J, Bobby Z, Chinnakali P. Effect of daily zinc supplementation for 12 weeks on serum thyroid auto-antibody levels in children and adolescents with autoimmune thyroiditis - a randomized controlled trial. J Pedi PubMed
  87. AlDhasee O, AlMalki H, AlKharashi N, AlJeraisy N, Al Deeb M. Acute zinc sulfate overdose: clinical presentation and management. BMJ Case Rep 2025;18(1):e263899. PubMed
  88. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Zinc monograph →

Selenium 36 references
  1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  2. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  3. Trafikowska U, Zachara BA, Wiacek M, et al. Selenium supply and glutathione peroxidase activity in breastfed Polish infants. Acta Paediatr 1996;85:1143-5. PubMed
  4. Duffield-Lillico AJ, Slate EH, Reid ME, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 2003;95:1477-81.. PubMed
  5. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  6. Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96. PubMed
  7. Davila JC, Edds GT, Osuna O, Simpson CF. Modification of the effects of aflatoxin B1 and warfarin in young pigs given selenium. Am J Vet Res 1983;44:1877-83. DOI
  8. Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in healthy nulliparas. S Afr Med J 1988;73:163-5.
  9. Lloyd B, Lloyd RS, Clayton BE. Effect of smoking, alcohol and other factors on the selenium status of a healthy population. J Epidemiol Commun Health 1983;37:213-7. PubMed
  10. Capel ID, Jenner M, Williams DC, et al. The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity. J Steroid Biochem 1981;14:729-32. PubMed
  11. Contempre B, Dumont JE, Ngo B, et al. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol PubMed
  12. Hofbauer LC, Spitzweg C, Magerstadt RA, Heufelder AE. Selenium-induced thyroid dysfunction. Postgrad Med J 1997;73:103-4. PubMed
  13. Debski B, Milner JA. Dietary selenium supplementation prolongs pentobarbital induced hypnosis. J Nutr Biochem 2004;15:548-53. PubMed
  14. Ishikawa M, Sasaki M, Koiwai K, et al. Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. J Pharmacobiodyn 1992;15:377-85. PubMed
  15. Lippmann SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial (SELECT). JAMA 2009;301:39-51. DOI
  16. Reid SM, Middleton P, Cossich MC, Crowther CA. Interventions for clinical and subclinical hypothyroidism in pregnancy. Cochrane Database Syst Rev 2010;(7):CD007752. PubMed
  17. Vinceti, M., Wei, E. T., Malagoli, C., Bergomi, M., and Vivoli, G. Adverse health effects of selenium in humans. Rev.Environ.Health 2001;16(4):233-251. PubMed
  18. Abrams, C. K., Siram, S. M., Galsim, C., Johnson-Hamilton, H., Munford, F. L., and Mezghebe, H. Selenium deficiency in long-term total parenteral nutrition. Nutr Clin Pract 1992;7(4):175-178. PubMed
  19. Spiller, H. A. and Pfiefer, E. Two fatal cases of selenium toxicity. Forensic Sci Int 8-24-2007;171(1):67-72. PubMed
  20. Negro, R., Greco, G., Mangieri, T., Pezzarossa, A., Dazzi, D., and Hassan, H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol.Metab 2007;92(4):1263-1268. PubMed
  21. Alexander, J. Selenium. Novartis.Found.Symp 2007;282:143-149.
  22. Salonen, J. T., Salonen, R., Seppanen, K., Rinta-Kiikka, S., Kuukka, M., Korpela, H., Alfthan, G., Kantola, M., and Schalch, W. Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial
  23. Kupka, R., Mugusi, F., Aboud, S., Msamanga, G. I., Finkelstein, J. L., Spiegelman, D., and Fawzi, W. W. Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and chil
  24. Kamble, P., Mohsin, N., Jha, A., Date, A., Upadhaya, A., Mohammad, E., Khalil, M., Pakkyara, A., and Budruddin, M. Selenium intoxication with selenite broth resulting in acute renal failure and severe gastritis. Saudi.J Kidney Dis.Transpl. 2009;20(1):106
  25. Peretz, A., Neve, J., Desmedt, J., Duchateau, J., Dramaix, M., and Famaey, J. P. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am.J Clin.Nutr. 1991;53(5):1323-1328. PubMed
  26. Kumpulainen, J., Salmenpera, L., Siimes, M. A., Koivistoinen, P., and Perheentupa, J. Selenium status of exclusively breast-fed infants as influenced by maternal organic or inorganic selenium supplementation. Am.J Clin.Nutr. 1985;42(5):829-835. PubMed
  27. Han, L. and Zhou, S. M. Selenium supplement in the prevention of pregnancy induced hypertension. Chin Med J (Engl) 1994;107(11):870-871.
  28. Kiremidjian-Schumacher, L., Roy, M., Wishe, H. I., Cohen, M. W., and Stotzky, G. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol.Trace Elem.Res. 1994;41(1-2):115-127. PubMed
  29. Srivastava, A. K., Gupta, B. N., Bihari, V., and Gaur, J. S. Generalized hair loss and selenium exposure. Vet.Hum.Toxicol. 1995;37(5):468-469.
  30. Sudfeld CR, Aboud S, Kupka R, et al. Effect of selenium supplementation on HIV-1 RNA detection in breast milk of Tanzanian women. Nutrition 2014;30(9):1081-4. PubMed
  31. Rees K, Hartley L, Day C, et al. Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;1:CD009671. PubMed
  32. Thompson PA, Ashbeck EL, Roe DJ, et al. Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes. J Natl Cancer Inst. 2016;108(12). PubMed
  33. Wichman J, Winther KH, Bonnema SJ, Hegedüs L. Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: a systematic review and meta-analysis. Thyroid 2016;26(12):1681-92. PubMed
  34. Vinceti M, Filippini T, Rothman KJ. Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis. Eur J Epidemiol. 2018 Sep;33(9):789-810. Epub 2018 Jul 5. Review. PubMed
  35. Fallah S, Sani FV, Firoozrai M. Effect of contraceptive pill on the selenium and zinc status of healthy subjects. Contraception. 2009;80(1):40-3. PubMed
  36. Malpas CB, Vivash L, Genc S, et al. A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate Alzheimer's Disease. J Alzheimers Dis. 2016;54(1):223-232. PubMed

See these in context on the Selenium monograph →

5-htp 32 references
  1. Birdsall TC. 5-Hydroxytryptophan: A Clinically-Effective Serotonin Precursor. Altern Med Rev 1998;3:271-80.
  2. Michelson D, Page SW, Casey R, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol 1994;21:2261-5.
  3. Cangiano C, Ceci F, Cancino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992;56:863-7. PubMed
  4. U.S. Food and Drug Administration. Impurities confirmed in dietary supplement 5-hydroxy-L-tryptophan. FDA Talk Paper, August 31, 1998; T98-48.
  5. Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med 1980;303:782-7. PubMed
  6. Poldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24:53-81.
  7. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache 2000;40:451-6.
  8. U. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. Information Paper on L-Tryptophan and 5-hydroxy-L-tryptophan, February 2001.
  9. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  10. Johnson KL, Klarskov K, Benson LM, et al. Presence of peak X and related compounds: the reported contaminant in case related 5-hydroxy-L-tryptophan associated with eosinophilia-myalgia syndrome. J Rheumatol 1999;26:2714-7.
  11. Takahashi S, Kondo H, Kato N. Effect of l-5-hydroxytryptophan on brain monoamine metabolism and evaluation of its clinical effect in depressed patients. J Psychiatr Res 1975;12:177-87. PubMed
  12. Iovieno, N., Dalton, E. D., Fava, M., and Mischoulon, D. Second-tier natural antidepressants: review and critique. J Affect.Disord. 2011;130(3):343-357. PubMed
  13. den Boer JA, Westenberg HG. Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. Psychiatry Res 1990;31:267-78. PubMed
  14. Jangid P, Malik P, Singh P, Sharma M, Gulia AK. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr 2013;6:29-34. PubMed
  15. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm 1989;76:109-17. PubMed
  16. Angst J, Woggon B, Schoepf J. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr 1977;224:175-86. DOI
  17. Titus F, Dávalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol 1986;25:327-9. PubMed
  18. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci 1985;29:239-48.
  19. Van Woert, M. H., Rosenbaum, D., Howieson, J., and Bowers, M. B., Jr. Long-term therapy of myoclonus and other neurologic disorders with L-5- hydroxytryptophan and carbidopa. N Engl J Med 1-13-1977;296(2):70-75. PubMed
  20. Wyatt, R. J., Vaughan, T., Galanter, M., Kaplan, J., and Green, R. Behavioral changes of chronic schizophrenic patients given L-5- hydroxytryptophan. Science 9-22-1972;177(54):1124-1126. PubMed
  21. Chase, T. N., Ng, L. K., and Watanabe, A. M. Parkinson's disease. Modification by 5-hydroxytryptophan. Neurology 1972;22(5):479-484.
  22. van Hiele LJ. l-5-Hydroxytryptophan in depression: the first substitution therapy in psychiatry? The treatment of 99 out-patients with 'therapy-resistant' depressions. Neuropsychobiology 1980;6:230-40. PubMed
  23. Pranzatelli, M. R., Tate, E., Huang, Y., Haas, R. H., Bodensteiner, J., Ashwal, S., and Franz, D. Neuropharmacology of progressive myoclonus epilepsy: response to 5- hydroxy-L-tryptophan. Epilepsia 1995;36(8):783-791. PubMed
  24. Trouillas P, Serratrice G, Laplane D, et al. Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study. Arch Neurol 1995;52:456-60. PubMed
  25. Bastard, J., Truelle, J. L., and Emile, J. [Effectiveness of 5 hydroxy-tryptophan in Parkinson's disease]. Nouv Presse Med 9-11-1976;5(29):1836-1837.
  26. Auffret, M., Comte, H., and Bene, J. Eosinophilia-myalgia syndrome induced by L-5 hydroxytryptophane: about three cases. Fund Clin Pharmacol 2013;Suppl 1(120):poster P2-204.
  27. Wyatt, R. J., Vaughan, T., Kaplan, J., Galanter, M., and Green, R. 5-Hydroxytryptophan and chronic schizophrenia. In: Barchas J and Usdin E. Serotonin and Behavior. New York: Acedemic Press;1973.
  28. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett 2004;150:111-22. PubMed
  29. Pardo JV. Mania following addition of hydroxytryptophan to monoamine oxidase inhibitor. Gen Hosp Psychiatry 2012;34(1):102.e13-4. PubMed
  30. Michelson D, Page SW, Casey R, et al. An eosinophilia-myaligia syndrome related disorder associated with exposure to l-5-hydroxytryptophan. J Rheumatol 1994;21(12):2261-5.
  31. Yousefzadeh F, Sahebolzamani E, Sadri A, et al. 5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control. Int Clin Psychopharmacol. 2020;35(5):254-262. PubMed
  32. Maffei ME. 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. Int J Mol Sci. 2020;22(1):181. PubMed

See these in context on the 5-htp monograph →

Ginkgo 97 references
  1. Davydov L, Stirling AL. Stevens-Johnson syndrome with Ginkgo biloba. J Herb Pharmacother 2001;1:65-9. DOI
  2. Benjamin J, Muir T, Briggs K, Pentland B. A case of cerebral haemorrhage-can Ginkgo biloba be implicated? Postgrad Med J 2001;77:112-3.
  3. Matthews, MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998;50:1934.
  4. Rowin J, Lewis SL. Spontaneous bilateral subdural hemotomas with chronic Ginkgo biloba ingestion. Neurology 1996;46:1775-6.
  5. Rosenblatt M, Mindel T. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med 1997;336:1108.
  6. Fessenden JM, Wittenborn W, Clarke L. Gingko biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy. Am Surg 2001;67:33-5. DOI
  7. Gurley BJ, Gardner SF, Hubbard MA. Clinical assessment of potential cytochrome P450-mediated herb-drug interactions. AAPS Ann Mtg & Expo Indianapolis, IN: 2000; Oct 29 - Nov 2:presentation #3460.
  8. Cohen AJ, Bartlik B. Ginkgo biloba for antidepressant-induced sexual dysfunction. J Sex Marital Ther 1998;24:139-43. PubMed
  9. Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract on pancreatic beta-cell function in response to glucose loading in normal glucose tolerant individuals. J Clin Pharmacol 2000;40:647-54.
  10. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7. DOI
  11. Cesarani A, Meloni F, Alpini D, et al. Ginkgo biloba (EGb 761) in the treatment of equilibrium disorders. Adv Ther 1998;15:291-304.
  12. Galluzzi S, Zanetti O, Binetti G, et al. Coma in a patient with Alzheimer's disease taking low dose trazodone and Ginkgo biloba. J Neurol Neurosurg Psychiatry 2000;68:679-80. DOI
  13. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  14. Gregory PJ. Seizure associated with Ginkgo biloba? Ann Intern Med 2001;134:344.
  15. Granger AS. Ginkgo biloba precipitating epileptic seizures. Age Ageing 2001;30:523-5. PubMed
  16. Kajiyama Y, Fujii K, Takeuchi H, Manabe Y. Ginkgo seed poisoning. Pediatrics 2002;109:325-7. PubMed
  17. Miwa H, Iijima M, Tanaka S, Mizuno Y. Generalized convulsions after consuming a large amount of gingko nuts. Epilepsia 2001;42:280-1. DOI
  18. Burschka MA, Hassan HA, Reineke T, et al. Effect of treatment with Ginkgo biloba extract EGb 761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients. Eur Arch Otorhinolaryngol 2001;258:213- PubMed
  19. Miller LG, Freeman B. Possible subdural hematoma associated with Ginkgo biloba. J Herb Pharmacother 2002;2:57-63.
  20. Kudolo GB, Dorsey S, Blodgett J. Effect of the ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and Type 2 diabetic subjects. Thromb Res 2002;108:151-60.. PubMed
  21. Fong KC, Kinnear PE. Retrobulbar haemorrhage associated with chronic Ginkgo biloba ingestion. Postgrad Med J 2003;79:531-2..
  22. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87.. PubMed
  23. Kang BJ, Lee SJ, Kim MD, Cho MJ. A placebo-controlled, double-blind trial of Ginkgo biloba for antidepressant-induced sexual dysfunction. Hum Psychopharmacol 2002;17:279-84.
  24. Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005;11:433-9.
  25. Yasui-Furukori N, Furukori H, Kaneda A, et al. The effects of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of donepezil. J Clin Pharmacol 2004;44:538-42.
  26. Markowitz JS, Donovan JL, Lindsay DeVane C, et al. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers. J Clin Psychopharmacol 2003;23:576-81. PubMed
  27. Arenz A, Kelin M, Flehe K, et al. Occurrence of neurotoxic 4'-O-methylpyridoxine in ginkgo biloba leaves, ginkgo medications and Japanese ginkgo food. Planta Med 1996;62:548-51.
  28. Engelsen J, Nielsen JD, Winther K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thromb Haemost 2002;87:1075-6. DOI
  29. Gaudineau C, Beckerman R, Welbourn S, Auclair K. Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Comm 2004;318:1072–8. PubMed
  30. Kohler S, Funk P, Kieser M. Influence of a 7-day treatment with Ginkgo biloba special extract EGb 761 on bleeding time and coagulation: a randomized, placebo-controlled, double-blind study in healthy volunteers. Blood Coagul Fibrinolysis 2004;15:303–9. PubMed
  31. Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005;59:425-32. PubMed
  32. Destro MW, Speranzini MB, Cavalheiro Filho C, et al. Bilateral haematoma after rhytidoplasty and blepharoplasty following chronic use of Ginkgo biloba. Br J Plast Surg 2005;58:100-1. PubMed
  33. Yin OQ, Tomlinson B, Waye MM, et al. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004;14:841-50. PubMed
  34. Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with Ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med 2005;20;657-61. DOI
  35. Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen. Atherosclerosis 2003;167:367. PubMed
  36. Bebbington A, Kulkarni R, Roberts P. Ginkgo biloba: Persistent bleeding after total hip arthroplasty caused by herbal self-medication. J Arthroplasty 2005;20:125-6. .
  37. Kupiec T, Raj V. Fatal seizures due to potential herb-drug interactions with Ginkgo biloba. J Anal Toxicol 2005:755-8. PubMed
  38. Hauser D, Gayowski T, Singh N. Bleeding complications precipitated by unrecognized Gingko biloba use after liver transplantation. Transpl Int 2002;15:377-9. DOI
  39. Mohutsky MA, Anderson GD, Miller JW, Elmer GW. Ginkgo biloba: evaluation of CYP2C9 drug interactions in vitro and in vivo. Am J Ther 2006;13:24-31. PubMed
  40. Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract (EGb 761) on pancreatic beta-cell function in response to glucose loading in individuals with non-insulin-dependent diabetes mellitus. J Clin Pharmacol 2001;41:600-11.
  41. Pennisi RS. Acute generalised exanthematous pustulosis induced by the herbal remedy Ginkgo biloba. Med J Aust 2006;184:583-4. PubMed
  42. Yagmur E, Piatkowski A, Groger A, et al. Bleeding complication under Gingko biloba medication. Am J Hematol 2005;79:343-4. PubMed
  43. Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 1998;352:36. PubMed
  44. Aruna D, Naidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol 2007;63:333-8.
  45. Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of ginkgo (Ginkgo biloba) during pregnancy and lactation. Can J Clin Pharmacol 2006;13:e277-84.
  46. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8. PubMed
  47. Woelk H, Arnoldt KH, Kieser M, Hoerr R. Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial. J Psychiatr Res 2007;41:472-80. PubMed
  48. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia. JAMA 2008;300:2253-62.
  49. Dodge HH, Zitzelberger T, Oken BS, et al. A randomized placebo-controlled trial of ginkgo biloba for the prevention of cognitive decline. Neurology 2008;70(19 Pt 2):1809-17. PubMed
  50. Wiegman DJ, Brinkman K, Franssen EJ. Interaction of Ginkgo biloba with efavirenz. AIDS 2009;23:1184-5. PubMed
  51. Kim BH, Kim KP, Lim KS, et al. Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: An open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy Kor
  52. Salehi B, Imani R, Mohammadi MR, et al. Ginkgo biloba for attention-deficit/hyperactivity disorder in children and adolescents: a double blind, randomized controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:76-80. PubMed
  53. Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy 2011;31:490-502.
  54. Kuller LH, Ives DG, Fitzpatrick AL, et al. Does Ginkgo biloba reduce the risk of cardiovascular events? Circ Cardiovasc Qual Outcomes 2010;3:41-7.
  55. Naccarato M, Yoong D, Gough K. A potential drug-herbal interaction between Ginkgo biloba and efavirenz. J Int Assoc Physicians AIDS Care (Chic). 2012;11(2):98-100. doi: 10.1177/1545109711435364. Epub 2012 Feb 9.
  56. Engelsen, J., Nielsen, J. D., and Hansen, K. F. [Effect of Coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial]. Ugeskr.Laeger 4-28-2003;165(18):18
  57. Parsad, D., Pandhi, R., and Juneja, A. Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo. Clin Exp.Dermatol. 2003;28(3):285-287.
  58. Bal Dit, Sollier C., Caplain, H., and Drouet, L. No alteration in platelet function or coagulation induced by EGb761 in a controlled study. Clin Lab Haematol. 2003;25(4):251-253. PubMed
  59. Yoshioka, M., Ohnishi, N., Koishi, T., Obata, Y., Nakagawa, M., Matsumoto, T., Tagagi, K., Takara, K., Ohkuni, T., Yokoyama, T., and Kuroda, K. Studies on interactions between functional foods or dietary supplements and medicines. IV. Effects of ginkgo b
  60. Yoshioka, M., Ohnishi, N., Sone, N., Egami, S., Takara, K., Yokoyama, T., and Kuroda, K. Studies on interactions between functional foods or dietary supplements and medicines. III. Effects of ginkgo biloba leaf extract on the pharmacokinetics of nifedipi
  61. Lovera, J., Bagert, B., Smoot, K., Morris, C. D., Frank, R., Bogardus, K., Wild, K., Oken, B., Whitham, R., and Bourdette, D. Ginkgo biloba for the improvement of cognitive performance in multiple sclerosis: a randomized, placebo-controlled trial. Mult.S PubMed
  62. Lin, Y. Y., Chu, S. J., and Tsai, S. H. Association between priapism and concurrent use of risperidone and Ginkgo biloba. Mayo Clin Proc 2007;82(10):1289-1290.
  63. Robertson, S. M., Davey, R. T., Voell, J., Formentini, E., Alfaro, R. M., and Penzak, S. R. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 2008;24(2):591-599. PubMed
  64. Penzak, S. R., Busse, K. H., Robertson, S. M., Formentini, E., Alfaro, R. M., and Davey, R. T., Jr. Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions. J Clin Pharmacol 2008;48(6):671-680. PubMed
  65. May, B. H., Yang, A. W., Zhang, A. L., Owens, M. D., Bennett, L., Head, R., Cobiac, L., Li, C. G., Hugel, H., Story, D. F., and Xue, C. C. Chinese herbal medicine for Mild Cognitive Impairment and Age Associated Memory Impairment: a review of randomised
  66. Choi, W. S., Choi, C. J., Kim, K. S., Lee, J. H., Song, C. H., Chung, J. H., Ock, S. M., Lee, J. B., and Kim, C. M. To compare the efficacy and safety of nifedipine sustained release with Ginkgo biloba extract to treat patients with primary Raynaud's phe
  67. Lei, H. P., Wang, G., Wang, L. S., Ou-yang, D. S., Chen, H., Li, Q., Zhang, W., Tan, Z. R., Fan, L., He, Y. J., and Zhou, H. H. Lack of effect of Ginkgo biloba on voriconazole pharmacokinetics in Chinese volunteers identified as CYP2C19 poor and extensiv
  68. Russo, V., Stella, A., Appezzati, L., Barone, A., Stagni, E., Roszkowska, A., and Delle, Noci N. Clinical efficacy of a Ginkgo biloba extract in the topical treatment of allergic conjunctivitis. Eur J Ophthalmol. 2009;19(3):331-336. PubMed
  69. Fan, L., Tao, G. Y., Wang, G., Chen, Y., Zhang, W., He, Y. J., Li, Q., Lei, H. P., Jiang, F., Hu, D. L., Huang, Y. F., and Zhou, H. H. Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers. Ann Phar PubMed
  70. Ozgoli, G., Selselei, E. A., Mojab, F., and Majd, H. A. A randomized, placebo-controlled trial of Ginkgo biloba L. in treatment of premenstrual syndrome. J Altern.Complement Med 2009;15(8):845-851.
  71. Singh, V., Singh, S. P., and Chan, K. Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia. Int J Neuropsychopharmacol. 2010;13(2):257-271.
  72. Kim, T. E., Kim, B. H., Kim, J., Kim, K. P., Yi, S., Shin, H. S., Lee, Y. O., Lee, K. H., Shin, S. G., Jang, I. J., and Yu, K. S. Comparison of the pharmacokinetics of ticlopidine between administration of a combined fixed-dose tablet formulation of ticl
  73. Nicolai, S. P., Gerardu, V. C., Kruidenier, L. M., Prins, M. H., and Teijink, J. A. From the Cochrane library: Ginkgo biloba for intermittent claudication. Vasa 2010;39(2):153-158. PubMed
  74. Patel, N. Herbal remedies. Br.Dent.J 8-28-2010;209(4):153.
  75. Pedroso, J. L., Henriques Aquino, C. C., Escorcio Bezerra, M. L., Baiense, R. F., Suarez, M. M., Dutra, L. A., Braga-Neto, P., and Povoas Barsottini, O. G. Ginkgo biloba and cerebral bleeding: a case report and critical review. Neurologist. 2011;17(2):89 PubMed
  76. Russo, V., Rago, A., Russo, G. M., Calabro, R., and Nigro, G. Ginkgo biloba: an ancient tree with new arrhythmic side effects. J Postgrad.Med 2011;57(3):221.
  77. Zhou, Y. and Zeng, R. [Effects of Ginkgo biloba extract on anticoagulation and blood drug level of warfarin in healthy wolunteers]. Zhongguo Zhong Yao Za Zhi 2011;36(16):2290-2293. DOI
  78. Skogh, M. Extracts of Ginkgo biloba and bleeding or haemorrhage. Lancet 10-3-1998;352(9134):1145-1146. PubMed
  79. Fessenden JM, Wittenborn W, and Clarke L. Ginkgo biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy. Am Surg 2001;67(1):33-35.
  80. Burkard G. [The efficacy and safety of ginkgo biloba extract in dementia]. Fortschr Med [Supp] 1991;109(107):6-8.
  81. Dai LL, Fan L, Wu HZ, Tan ZR, Chen Y, Peng XD, Shen MX, Yang GP, Zhou HH. Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and Ginkgo biloba extracts in healthy subjects. Xenobiotica 2013;43(10):862-7.
  82. Guo CX, Pei Q, Yin JY, Peng XD, Zhou BT, Zhao YC, Wu LX, Meng XG, Wang G, Li Q, Ouyang DS, Liu ZQ, Zhang W, Zhou HH. Effects of Ginkgo biloba extracts on pharmacokinetics and efficacy of atorvastatin based on plasma indices. Xenobiotica 2012;42(8):784-90.
  83. Stoddard GJ, Archer M, Shane-McWhorter L, Bray BE, Redd DF, Proulx J, Zeng-Treitler Q. Ginkgo and Warfarin Interaction in a Large Veterans Administration Population. AMIA Annu Symp Proc. 2015 Nov 5;2015:1174-83.
  84. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  85. Carlile PV. Unexplained alveolar hemorrhage associated with ginkgo and ginseng use. J Bronchology Interv Pulmonol. 2015;22(2):170-2. doi: 10.1097/LBR.0000000000000150. PubMed
  86. Han EJ, Park HL, Kim SH. Allergic Reaction to Ginkgo Nut on FDG PET/CT. Clin Nucl Med. 2016 Sep;41(9):716-7. doi: 10.1097/RLU.0000000000001276. PubMed
  87. Rho SS, Woo YS, Bahk WM. Ginkgo biloba induced mood dysregulation: a case report. BMC Complement Altern Med. 2018 Jan 15;18(1):14. PubMed
  88. Aziz TA, Hussain SA, Mahwi TO, Ahmed ZA, Rahman HS, Rasedee A. The efficacy and safety of Ginkgo biloba extract as an adjuvant in type 2 diabetes mellitus patients ineffectively managed with metformin: a double-blind, randomized, placebo-controlled trial.
  89. World Health Organization. WHO pharmaceuticals newsletter: 2020, No. 3. Available at: https://www.who.int/medicines/publications/WHO_Pharmaceuticals_Newslet3_20.pdf?ua=1. Accessed June 23, 2021.
  90. Health Canada. Ginkgo biloba-containing products and the risk of cardiac arrhythmias. Health Product InfoWatch. February 2021. Available at: https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/health-product-infowatch/fe
  91. Wasef AK, Wahdan SA, Saeed NM, El-Demerdash E. Effects of aged garlic and ginkgo biloba extracts on the pharmacokinetics of sofosbuvir in rats. Biopharm Drug Dispos. 2022;43(4):152-62. PubMed
  92. Xing X, Kong M, Hou Q, Li J, Qian W, Chen X, Li H, Yang C. Effects of ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism. Pharm Biol. 2022;60(1):1190-7. PubMed
  93. Hoerr R, Zimmermann A, Seitz F, Dienel A. Single and repeated doses of EGb 761® do not affect pharmacokinetics or pharmacodynamics of rivaroxaban in healthy subjects. Front Pharmacol. 2022 Apr 20;13:868843. PubMed
  94. Bai J, Zhang C. Metabolic interaction between biflavonoids in Ginkgo biloba leaves and tacrolimus. Biopharm Drug Dispos 2023;44(2):157-164.
  95. Wang Q, Liu Z, Wang R, et al. Effect of Ginkgo biloba extract on pharmacology and pharmacokinetics of atorvastatin in rats with hyperlipidaemia. Food Funct 2023;14(7):3051-3066.
  96. Burnett CL, Bergfeld WF, Belsito DV, et al. Safety Assessment of Ginkgo biloba-Derived Ingredients as Used in Cosmetics. Int J Toxicol. 2023 Nov 6:10915818231210792.
  97. Yao Y, Zhao J, Li C, et al. Ginkgo biloba extract safety: Insights from a real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events. J Ethnopharmacol 2025;337(Pt 3):119010. PubMed

See these in context on the Ginkgo monograph →

Green Tea 219 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Mitscher LA, Mitscher LA, Jung M, Shankel D, et al. Chemoprotection: a review of the potential therapeutic antioxidant properties of green tea (Camellia sinensis) and certain of its constituents. Med Res Rev 1997;17:327-65.
  8. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  9. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  10. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  11. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  12. Booth SL, Madabushi HT, Davidson KW, et al. Tea and coffee brews are not dietary sources of vitamin K-1 (phylloquinone). J Am Diet Assoc 1995;95:82-3. PubMed
  13. Lou FQ, Zhang MF, Zhang XG, et al. A study on tea-pigment in prevention of atherosclerosis. Chin Med J (Engl) 1989;102:579-83.
  14. Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med 1992;21:334-50. PubMed
  15. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  16. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  17. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  18. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  19. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed
  20. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  21. Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. PubMed
  22. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  23. Weisburger JH. Tea and health: the underlying mechanisms. Proc Soc Exp Biol Med 1999;220:271-5. PubMed
  24. Taylor JR, Wilt VM. Probable antagonism of warfarin by green tea. Ann Pharmacother 1999;33:426-8. PubMed
  25. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  26. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  27. Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. PubMed
  28. Lloyd T, Johnson-Rollings N, Eggli DF, et al. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr 2000;19:256-61. PubMed
  29. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  30. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7. DOI
  31. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  32. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  33. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  34. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  35. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 1996:144:642-4. PubMed
  36. Pisters KM, Newman RA, Coldman B, et al. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol 2001;19:1830-8. PubMed
  37. Haller CA, Jacob P 3rd, Benowitz NL. Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clin Pharmacol Ther 2002;71:421-32. PubMed
  38. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. PubMed
  39. Horner NK, Lampe JW. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness. J Am Diet Assoc 2000;100:1368-80. PubMed
  40. Bracken MB, Triche EW, Belanger K, et al. Association of maternal caffeine consumption with decrements in fetal growth. Am J Epidemiol 2003;157:456-66.. PubMed
  41. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  42. Nehlig A, Debry G. Consequences on the newborn of chronic maternal consumption of coffee during gestation and lactation: a review. J Am Coll Nutr 1994;13:6-21.. PubMed
  43. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  44. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  45. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI
  46. Ahn WS, Yoo J, Huh SW, et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev 2003;12:383-90. PubMed
  47. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  48. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  49. Shirai T, Hayakawa H, Akiyama J, et al. Food allergy to green tea. J Allergy Clin Immunol 2003;112:805-6. PubMed
  50. Jatoi A, Ellison N, Burch PA, et al. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer 2003;97:1442-6.. PubMed
  51. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  52. May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982;31:656-61. PubMed
  53. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  54. Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. DOI
  55. Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. PubMed
  56. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  57. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  58. Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. PubMed
  59. Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7.
  60. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
  61. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  62. Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. PubMed
  63. Yang YC, Lu FH, Wu JS, et al. The protective effect of habitual tea consumption on hypertension. Arch Intern Med 2004 26;164:1534-40. PubMed
  64. Son DJ, Cho MR, Jin YR, et al. Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway. Prostaglandins Leukot Essent Fatty Acids 2004;71:25-31. PubMed
  65. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004;176:1-29. PubMed
  66. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  67. Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. DOI
  68. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  69. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  70. Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med 2006;144:68-71.
  71. Gloro R, Hourmand-Ollivier I, Mosquet B, et al. Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea. Eur J Gastroenterol Hepatol 2005;17:1135-7. PubMed
  72. Donovan JL, Chavin KD, Devane CL, et al. Green tea (Camellia sinensis) extract does not alter cytochrome P450 3A4 or 2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:906-8. PubMed
  73. Chu KO, Wang CC, Chu CY, et al. Pharmacokinetic studies of green tea catechins in maternal plasma and fetuses in rats. J Pharm Sci 2006;95:1372-81. PubMed
  74. Isbrucker RA, Edwards JA, Wolz E, et al. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. Food Chem Toxicol 2006;44:651-61. PubMed
  75. Navarro-Peran E, Cabezas-Herrera J, Garcia-Canovas F, et al. The antifolate activity of tea catechins. Cancer Res 2005;65:2059-64. PubMed
  76. Jimenez-Saenz M, Martinez-Sanchez, MDC. Acute hepatitis associated with the use of green tea infusions. J Hepatol 2006;44:616-9. PubMed
  77. Bradley Pharmaceuticals. Veregen Prescribing Information. October 2006.
  78. Correa A, Stolley A, Liu Y. Prenatal tea consumption and risks of anencephaly and spina bifida. Ann Epidemiol 2000;10:476-7. PubMed
  79. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8. PubMed
  80. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  81. Golden ED, Lam PY, Kardosh A, et al. Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood 2009;113:5927-37. PubMed
  82. Misaka S, Yatabe J, Muller F, et al. Green Tea Ingestion Greatly Reduces Plasma Concentrations of Nadolol in Healthy Subjects. Clin Pharmacol Ther 2014. [Epub ahead of print]. PubMed
  83. Roth M, Timmermann BN, Hagenbuch B. Interactions of green tea catechins with organic anion-transporting polypeptides. Drug Metab Dispos 2011;39:920-6. PubMed
  84. Kato Y, Miyazaki T, Kano T, et al. Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci 2009;98:2529-39. PubMed
  85. Chan, H. T., So, L. T., Li, S. W., Siu, C. W., Lau, C. P., and Tse, H. F. Effect of herbal consumption on time in therapeutic range of warfarin therapy in patients with atrial fibrillation. J.Cardiovasc.Pharmacol. 2011;58(1):87-90. PubMed
  86. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extrac
  87. Shet, M. S., McPhaul, M., Fisher, C. W., Stallings, N. R., and Estabrook, R. W. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997;25(11):1298-1303.
  88. Staib, A. H., Stille, W., Dietlein, G., Shah, P. M., Harder, S., Mieke, S., and Beer, C. Interaction between quinolones and caffeine. Drugs 1987;34 Suppl 1:170-174. PubMed
  89. Stille, W., Harder, S., Mieke, S., Beer, C., Shah, P. M., Frech, K., and Staib, A. H. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J.Antimicrob.Chemother. 1987;20(5):729-734. PubMed
  90. Fuhr, U., Strobl, G., Manaut, F., Anders, E. M., Sorgel, F., Lopez-de-Brinas, E., Chu, D. T., Pernet, A. G., Mahr, G., Sanz, F., and . Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isof
  91. Kot, M. and Daniel, W. A. Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes. Pharmacol Rep. 2009;61(6):1216-1220. PubMed
  92. Gasior, M., Borowicz, K., Buszewicz, G., Kleinrok, Z., and Czuczwar, S. J. Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia 1996;37(3 PubMed
  93. Jankiewicz, K., Chroscinska-Krawczyk, M., Blaszczyk, B., and Czuczwar, S. J. [Caffeine and antiepileptic drugs: experimental and clinical data]. Przegl.Lek. 2007;64(11):965-967.
  94. Luszczki, J. J., Zuchora, M., Sawicka, K. M., Kozinska, J., and Czuczwar, S. J. Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures i
  95. Chroscinska-Krawczyk, M., Jargiello-Baszak, M., Walek, M., Tylus, B., and Czuczwar, S. J. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol.Rep. 2011;63(1):12-18. PubMed
  96. Vaz, J., Kulkarni, C., David, J., and Joseph, T. Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. Indian J.Exp.Biol. 1998;36(1):112-114.
  97. Gasior, M., Swiader, M., Przybylko, M., Borowicz, K., Turski, W. A., Kleinrok, Z., and Czuczwar, S. J. Felbamate demonstrates low propensity for interaction with methylxanthines and Ca2+ channel modulators against experimental seizures in mice. Eur.J Phar PubMed
  98. Mohiuddin, M., Azam, A. T., Amran, M. S., and Hossain, M. A. In vive effects of gliclazide and metformin on the plasma concentration of caffeine in healthy rats. Pak.J Biol Sci 5-1-2009;12(9):734-737.
  99. Mays, D. C., Camisa, C., Cheney, P., Pacula, C. M., Nawoot, S., and Gerber, N. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin.Pharmacol.Ther. 1987;42(6):621-626. PubMed
  100. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  101. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.
  102. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  103. Wang, X. and Yeung, J. H. Effects of the aqueous extract from Salvia miltiorrhiza Bunge on caffeine pharmacokinetics and liver microsomal CYP1A2 activity in humans and rats. J Pharm Pharmacol 2010;62(8):1077-1083.
  104. Kot M, Daniel WA. Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep 2008;60:789-97.
  105. Kjaerstad MB, Nielsen F, Nohr-Jensen L, et al. Systemic uptake of miconazole during vaginal suppository use and effect on CYP1A2 and CYP3A4 associated enzyme activities in women. Eur J Clin Pharmacol 2010;66:1189-97. PubMed
  106. Goh BC, Reddy NJ, Dandamudi UB, et al. An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid t
  107. Chen Y, Kang Z, Yan J, et al. Liu wei di huang wan, a well-known traditional Chinese medicine induces CYP1A2 while suppressing CYP2A6 and N-acetyltransferase 2 acivities in man. J Ethnopharmacol 2010;132:213-8.
  108. Suzuki S, Murayama Y, Sugiyama E, et al. Estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, based on physiological liver development and serum protein levels. Yakugaku Zasshi 2010;130:613-20. PubMed
  109. Chien CF, Wu YT, Lee WC, et al. Herb-drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats. Chem Biol Interact 2010;184:458-65. PubMed
  110. Mills BM, Zaya MJ, Walters RR, et al. Current cytochrome P450 phenotyping methods applied to metabolic drug -drug interaction prediction in dogs. Drug Metab Dispos 2010;38:396-404. PubMed
  111. Turpault S, Brian W, Van Horn R, et al. Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6, and 3A. Br J Clin Pharmacol 2009;68:928-35. PubMed
  112. Filimonova AA, Ziganshina LE, Ziganshin AU, Chichirov AA. On the possibility of patient phenotyping on the basis of cytochrome p-450 1A2 isoenzyme activity using caffeine as the test substrate. Eksp Klin Farmakol 2009;72:61-5.
  113. Jenkins J, Williams D, Deng Y, et al. Eltrombopag, an oral thrombopoietin receptor agonist, has no impact on the pharmacokinetic profile of probe drugs for cytochrome P450 isoenzymes CYP3A4, CYP1A2, CYP2C9 and CYP2C19 in healthy men: a cocktail analysis.
  114. Chow, H. H., Cai, Y., Hakim, I. A., Crowell, J. A., Shahi, F., Brooks, C. A., Dorr, R. T., Hara, Y., and Alberts, D. S. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E i
  115. Gross, G., Meyer, K. G., Pres, H., Thielert, C., Tawfik, H., and Mescheder, A. A randomized, double-blind, four-arm parallel-group, placebo-controlled Phase II/III study to investigate the clinical efficacy of two galenic formulations of Polyphenon E in
  116. Stockfleth, E., Beti, H., Orasan, R., Grigorian, F., Mescheder, A., Tawfik, H., and Thielert, C. Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial. Br.J Dermatol. 2008;158(6):1329-1338.
  117. Smits, P., Temme, L., and Thien, T. The cardiovascular interaction between caffeine and nicotine in humans. Clin Pharmacol Ther 1993;54(2):194-204. PubMed
  118. MacKenzie, T., Comi, R., Sluss, P., Keisari, R., Manwar, S., Kim, J., Larson, R., and Baron, J. A. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-1698. PubMed
  119. Lopez-Garcia, E., Rodriguez-Artalejo, F., Rexrode, K. M., Logroscino, G., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of stroke in women. Circulation 3-3-2009;119(8):1116-1123. PubMed
  120. Zhang, W., Lopez-Garcia, E., Li, T. Y., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of cardiovascular diseases and all-cause mortality among men with type 2 diabetes. Diabetes Care 2009;32(6):1043-1045. PubMed
  121. Moisey, L. L., Robinson, L. E., and Graham, T. E. Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males. Br.J Nutr. 2010;103(6):833-841. PubMed
  122. Chroscinska-Krawczyk, M., Ratnaraj, N., Patsalos, P. N., and Czuczwar, S. J. Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep. 2009;61(5):819 PubMed
  123. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  124. Buscemi, S., Verga, S., Batsis, J. A., Donatelli, M., Tranchina, M. R., Belmonte, S., Mattina, A., Re, A., and Cerasola, G. Acute effects of coffee on endothelial function in healthy subjects. Eur.J Clin Nutr. 2010;64(5):483-489. PubMed
  125. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  126. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  127. Conen, D., Chiuve, S. E., Everett, B. M., Zhang, S. M., Buring, J. E., and Albert, C. M. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr 2010;92(3):509-514. PubMed
  128. Reis, J. P., Loria, C. M., Steffen, L. M., Zhou, X., van, Horn L., Siscovick, D. S., Jacobs, D. R., Jr., and Carr, J. J. Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study. A PubMed
  129. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  130. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  131. Perera, V., Gross, A. S., and McLachlan, A. J. Caffeine and paraxanthine HPLC assay for CYP1A2 phenotype assessment using saliva and plasma. Biomed.Chromatogr. 2010;24(10):1136-1144. PubMed
  132. Orozco-Gregorio, H., Mota-Rojas, D., Bonilla-Jaime, H., Trujillo-Ortega, M. E., Becerril-Herrera, M., Hernandez-Gonzalez, R., and Villanueva-Garcia, D. Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia PubMed
  133. Izzo, A. A. and Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009;69(13):1777-1798. PubMed
  134. Laurie, S. A., Miller, V. A., Grant, S. C., Kris, M. G., and Ng, K. K. Phase I study of green tea extract in patients with advanced lung cancer. Cancer Chemother.Pharmacol. 2005;55(1):33-38. PubMed
  135. Chiu, A. E., Chan, J. L., Kern, D. G., Kohler, S., Rehmus, W. E., and Kimball, A. B. Double-blinded, placebo-controlled trial of green tea extracts in the clinical and histologic appearance of photoaging skin. Dermatol Surg. 2005;31(7 Pt 2):855-860. PubMed
  136. Javaid, A. and Bonkovsky, H. L. Hepatotoxicity due to extracts of Chinese green tea (Camellia sinensis): a growing concern. J Hepatol 2006;45(2):334-335. PubMed
  137. Martinez-Sierra, C., Rendon, Unceta P., and Martin, Herrera L. [Acute hepatitis after green tea ingestion]. Med Clin (Barc.) 6-17-2006;127(3):119.
  138. Molinari, M., Watt, K. D., Kruszyna, T., Nelson, R., Walsh, M., Huang, W. Y., Nashan, B., and Peltekian, K. Acute liver failure induced by green tea extracts: case report and review of the literature. Liver Transpl. 2006;12(12):1892-1895. PubMed
  139. Chow, H. H., Hakim, I. A., Vining, D. R., Crowell, J. A., Cordova, C. A., Chew, W. M., Xu, M. J., Hsu, C. H., Ranger-Moore, J., and Alberts, D. S. Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer Epidemiol.B PubMed
  140. Federico, A., Tiso, A., and Loguercio, C. A case of hepatotoxicity caused by green tea. Free Radic.Biol Med 8-1-2007;43(3):474. PubMed
  141. Sarma, D. N., Barrett, M. L., Chavez, M. L., Gardiner, P., Ko, R., Mahady, G. B., Marles, R. J., Pellicore, L. S., Giancaspro, G. I., and Low, Dog T. Safety of green tea extracts : a systematic review by the US Pharmacopeia. Drug Saf 2008;31(6):469-484. PubMed
  142. Engdal, S. and Nilsen, O. G. In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients. Phytother.Res. 2009;23(7):906-912.
  143. Bergman, J. and Schjott, J. Hepatitis caused by Lotus-f3? Basic Clin Pharmacol.Toxicol. 2009;104(5):414-416. PubMed
  144. Kalus, U., Kiesewetter, H., and Radtke, H. Effect of CYSTUS052 and green tea on subjective symptoms in patients with infection of the upper respiratory tract. Phytother.Res. 2010;24(1):96-100.
  145. Tatti, S., Stockfleth, E., Beutner, K. R., Tawfik, H., Elsasser, U., Weyrauch, P., and Mescheder, A. Polyphenon E: a new treatment for external anogenital warts. Br.J Dermatol. 2010;162(1):176-184.
  146. Tsao, A. S., Liu, D., Martin, J., Tang, X. M., Lee, J. J., El-Naggar, A. K., Wistuba, I., Culotta, K. S., Mao, L., Gillenwater, A., Sagesaka, Y. M., Hong, W. K., and Papadimitrakopoulou, V. Phase II randomized, placebo-controlled trial of green tea extra
  147. Liatsos, G. D., Moulakakis, A., Ketikoglou, I., and Klonari, S. Possible green tea-induced thrombotic thrombocytopenic purpura. Am.J Health Syst.Pharm. 4-1-2010;67(7):531-534. PubMed
  148. Josic, J., Olsson, A. T., Wickeberg, J., Lindstedt, S., and Hlebowicz, J. Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: a randomized controlled trial. Nutr.J. 2010;9:63. PubMed
  149. Miller, R. J., Jackson, K. G., Dadd, T., Mayes, A. E., Brown, A. L., and Minihane, A. M. The impact of the catechol-O-methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract. Br.J.Nutr. 2011;105(8):1138-1144.
  150. Rohde, J., Jacobsen, C., and Kromann-Andersen, H. [Toxic hepatitis triggered by green tea]. Ugeskr.Laeger 1-17-2011;173(3):205-206.
  151. Tzellos, T. G., Sardeli, C., Lallas, A., Papazisis, G., Chourdakis, M., and Kouvelas, D. Efficacy, safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta-analysis. J.Eur.Acad.Dermatol.Ve PubMed
  152. Otera, H., Tada, K., Sakurai, T., Hashimoto, K., and Ikeda, A. Hypersensitivity pneumonitis associated with inhalation of catechin-rich green tea extracts. Respiration 2011;82(4):388-392. PubMed
  153. Yellapu, R. K., Mittal, V., Grewal, P., Fiel, M., and Schiano, T. Acute liver failure caused by 'fat burners' and dietary supplements: a case report and literature review. Can.J.Gastroenterol. 2011;25(3):157-160. PubMed
  154. Karth, A., Holoshitz, N., Kavinsky, C. J., Trohman, R., and McBride, B. F. A case report of atrial fibrillation potentially induced by hydroxycut: a multicomponent dietary weight loss supplement devoid of sympathomimetic amines. J.Pharm.Pract. 2010;23(3) PubMed
  155. Hsu, C. H., Liao, Y. L., Lin, S. C., Tsai, T. H., Huang, C. J., and Chou, P. Does supplementation with green tea extract improve insulin resistance in obese type 2 diabetics? A randomized, double-blind, and placebo-controlled clinical trial. Altern.Med.R
  156. Zheng XX, Xu YL, Li SH, et al. Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials. Am.J.Clin.Nutr. 2011;94:601-610. PubMed
  157. Miller, R. J., Jackson, K. G., Dadd, T., Mayes, A. E., Brown, A. L., Lovegrove, J. A., and Minihane, A. M. The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion. Mol.Nutr.Food Res.
  158. Bogdanski, P., Suliburska, J., Szulinska, M., Stepien, M., Pupek-Musialik, D., and Jablecka, A. Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, h
  159. Jurgens, T. M., Whelan, A. M., Killian, L., Doucette, S., Kirk, S., and Foy, E. Green tea for weight loss and weight maintenance in overweight or obese adults. Cochrane.Database.Syst.Rev. 2012;12:CD008650. PubMed
  160. Sakamoto, O., Saita, N., Yamasaki, H., Tamanoi, M., and Ando, M. Pulmonary granulomatosis caused by aspirated green tea. Chest 1994;106(1):308-309. PubMed
  161. Jiménez-Encarnación E, Ríos G, Muñoz-Mirabal A, Vilá LM. Euforia-induced acute hepatitis in a patient with scleroderma. BMJ Case Rep 2012;2012. PubMed
  162. Choi JS, Burm JP. Effects of oral epigallocatechin gallate on the pharmacokinetics of nicardipine in rats. Arch Pharm Res. 2009 Dec;32(12):1721-5. PubMed
  163. Chung JH, Choi DH, Choi JS. Effects of oral epigallocatechin gallate on the oral pharmacokinetics of verapamil in rats. Biopharm Drug Dispos. 2009 Mar;30(2):90-3. PubMed
  164. Crew KD, Brown P, Greenlee H, Bevers TB, Arun B, Hudis C, McArthur HL, Chang J, Rimawi M, Vornik L, Cornelison TL, Wang A, Hibshoosh H, Ahmed A, Terry MB, Santella RM, Lippman SM, Hershman DL. Phase IB randomized, double-blinded, placebo-controlled, dose
  165. Dryden GW, Lam A, Beatty K, Qazzaz HH, McClain CJ. A pilot study to evaluate the safety and efficacy of an oral dose of (-)-epigallocatechin-3-gallate-rich polyphenon E in patients with mild to moderate ulcerative colitis. Inflamm Bowel Dis. 2013 Aug;19(9 PubMed
  166. Gallo E, Maggini V, Berardi M, Pugi A, Notaro R, Talini G, Vannozzi G, Bagnoli S, Forte P, Mugelli A, Annese V, Firenzuoli F, Vannacci A. Is green tea a potential trigger for autoimmune hepatitis? Phytomedicine. 2013 Oct 15;20(13):1186-9. PubMed
  167. Liu K, Zhou R, Wang B, Chen K, Shi LY, Zhu JD, Mi MT. Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr. 2013 Aug;98(2):340-8. PubMed
  168. Onakpoya I, Spencer E, Heneghan C, Thompson M. The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis. 2014 Aug;24:823-36. PubMed
  169. Patel SS, Beer S, Kearney DL, Phillips G, Carter BA. Green tea extract: a potential cause of acute liver failure. World J Gastroenterol. 2013 Aug 21;19(31):5174-7. PubMed
  170. Pillukat MH, Bester C, Hensel A, Lechtenberg M, Petereit F, Beckebaum S, Müller KM, Schmidt HH. Concentrated green tea extract induces severe acute hepatitis in a 63-year-old woman--a case report with pharmaceutical analysis. J Ethnopharmacol. 2014 Aug 8; PubMed
  171. Schönthal AH. Adverse effects of concentrated green tea extracts. Mol Nutr Food Res. 2011 Jun;55(6):874-85. PubMed
  172. Shiraishi M, Haruna M, Matsuzaki M, Ota E, Murayama R, Murashima S. Association between the serum folate levels and tea consumption during pregnancy. Biosci Trends. 2010 Oct;4(5):225-30.
  173. Jang EH, Choi JY, Park CS, Lee SK, Kim CE, Park HJ, Kang JS, Lee JW, Kang JH. Effects of green tea extract administration on the pharmacokinetics of clozapine in rats. J Pharm Pharmacol. 2005 Mar;57(3):311-6. PubMed
  174. Trudel D, Labbé DP, Araya-Farias M, Doyen A, Bazinet L, Duchesne T, Plante M, Grégoire J, Renaud MC, Bachvarov D, Têtu B, Bairati I. A two-stage, single-arm, phase II study of EGCG-enriched green tea drink as a maintenance therapy in women with advanced s
  175. Zheng XX, Xu YL, Li SH, Hui R, Wu YJ, Huang XH. Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2013 Apr;97(4):750-62. PubMed
  176. Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J. Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart. 2013;99(19):1383-9. doi: 10.1136/heartjnl-2013-303950. Re PubMed
  177. Cheng M, Hu Z, Lu X, Huang J, Gu D. Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies. Can J Cardiol. 2014 Apr;30(4):448-54. doi: 10.1016/j.cjca.2013.12.026. Epub 2014 2. Review. PubMed
  178. van der Hoeven N, Visser I, Schene A, van den Born BJ. Severe hypertension related to caffeinated coffee and tranylcypromine: a case report. Ann Intern Med. 2014 May 6;160(9):657-8. doi: 10.7326/L14-5009-8. No abstract available. PubMed
  179. Dixit S, Stein PK, Dewland TA, Dukes JW, Vittinghoff E, Heckbert SR, Marcus GM. Consumption of Caffeinated Products and Cardiac Ectopy. J Am Heart Assoc. 2016 26;5(1). pii: e002503. doi: 10.1161/JAHA.115.002503. PubMed
  180. Health Canada. Health Product Info Watch. October 2016; 5-6. Available at: http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/hpiw-ivps_2016-10-eng.php#a15.
  181. Green Tea Extract-Containing Natural Health Products - Rare Risk of Serious Liver Injury. Recalls & alerts. November 15, 2017. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/65100a-eng.php. Accessed November 10, 2017.
  182. Mazzanti G, Di Sotto A, Vitalone A. Hepatotoxicity of green tea: an update. Arch Toxicol. 2015;89(8):1175-91. PubMed
  183. Isomura T, Suzuki S, Origasa H, et al. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. Eur J Clin Nutr. 2016;70(11):1221-1229. PubMed
  184. Drug Record: Green Tea (Camellia Sinesis). LiverTox: National Institutes of Health, U.S. Department of Health & Human Services, March 2014. https://livertox.nlm.nih.gov//GreenTea.htm. Accessed November 20, 2017.
  185. Yates AA, Erdman JW Jr, Shao A, Dolan LC, Griffiths JC. Bioactive nutrients - Time for tolerable upper intake levels to address safety. Regul Toxicol Pharmacol. 2017;84:94-101. PubMed
  186. Younes M, Aggett P, Aguilar F, et al. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Scientific opinion on the safety of green tea catechins. EFSA Journal 2018;16(4):5239. PubMed
  187. Zuchinali P, Riberio PA, Pimentel M, da Rosa PR, Zimerman LI, Rohde LE. Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies. Europace 2016 Feb;18(2):257-66. PubMed
  188. Dostal AM, Samavat H, Bedell S, et al. The safety of green tea extract supplementation in postmenopausal women at risk for breast cancer: results of the Minnesota Green Tea Trial. Food Chem Toxicol. 2015 Sep;83:26-35. PubMed
  189. Shamekhi Z, Amani R, Habibagahi Z, Namjoyan F, Ghadiri A, Saki Malehi A. A Randomized, Double-blind, Placebo-controlled Clinical Trial Examining the Effects of Green Tea Extract on Systemic Lupus Erythematosus Disease Activity and Quality of Life. Phytoth PubMed
  190. Lagier D, Nee L, Guieu R, et al. Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: a randomized controlled clinical trial. Eur J Anaesthesiol. 2018 Apr 26. [Epub ahead of DOI
  191. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  192. Chong SJ, Howard KA, Knox C. Hypokalaemia and drinking green tea: a literature review and report of 2 cases. BMJ Case Rep. 2016;2016. pii: bcr2016214425. PubMed
  193. Qiao J, Gu C, Shang W, et al. Effect of green tea on pharmacokinetics of 5-fluorouracil in rats and pharmacodynamics in human cell lines in vitro. Food Chem Toxicol. 2011;49(6):1410-5. PubMed
  194. Abe O, Ono T, Sato H, et al. Role of (-)-epigallocatechin gallate in the pharmacokinetic interaction between nadolol and green tea in healthy volunteers. Eur J Clin Pharmacol 2018;74(6):775-83. doi: 10.1007/s00228-018-2436-2. PubMed
  195. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648. PubMed
  196. Nutescu EA, Shapiro NL, Ibrahim S, et al. Warfarin and its interactions with foods, herbs and other dietary supplements. Expert Opin Drug Saf. 2006;5(3):433-51. PubMed
  197. Abdelkawy KS, Abdelaziz RM, Abdelmageed AM, Donia AM, El-Khodary NM. Effects of green tea extract on atorvastatin pharmacokinetics in healthy volunteers. Eur J Drug Metab Pharmacokinet. 2020;45(3):351-360. PubMed
  198. Filippini T, Malavolti M, Borrelli F, et al. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Rev. 2020;3(3):CD005004. PubMed
  199. Huang S, Xu Q, Liu L, et al. Effect of green tea and (-)-epigallocatechin gallate on the pharmacokinetics of rosuvastatin. Curr Drug Metab. 2020. PubMed
  200. Mahmoodi M, Hosseini R, Kazemi A, Ofori-Asenso R, Mazidi M, Mazloomi SM. Effects of green tea or green tea catechin on liver enzymes in healthy individuals and people with nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomiz
  201. Misaka S, Abe O, Ono T, et al. Effects of single green tea ingestion on pharmacokinetics of nadolol in healthy volunteers. Br J Clin Pharmacol. 2020. PubMed
  202. Oketch-Rabah HA, Roe AL, Rider CV, et al. United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts. Toxicol Rep. 2020;7:386-402. PubMed
  203. Kim TE, Ha N, Kim Y, et al. Effect of epigallocatechin-3-gallate, major ingredient of green tea, on the pharmacokinetics of rosuvastatin in healthy volunteers. Drug Des Devel Ther. 2017;11:1409-1416. PubMed
  204. Misaka S, Ono Y, Uchida A, et al. Impact of green tea catechin ingestion on the pharmacokinetics of lisinopril in healthy volunteers. Clin Transl Sci. 2020. PubMed
  205. Darweesh RS, El-Elimat T, Zayed A, et al. The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats. BMC Pharmacol Toxicol. 2020;21(1):77. PubMed
  206. Sonoda J, Ogata K, Yoshikawa N, Sato K, Ikeda R, Shimodozono Y. Impact of green tea intake on the pharmacokinetics of celiprolol in healthy subjects. Int J Clin Pharmacol Ther. 2020. PubMed
  207. Kim S, Park TH, Kim WI, Park S, Kim JH, Cho MK. The effects of green tea on acne vulgaris: A systematic review and meta-analysis of randomized clinical trials. Phytother Res. 2021;35(1):374-383. PubMed
  208. Percevault S, Charpiat B, Lebossé F, Mabrut JY, Vial T, Colom M. Green tea and hepatoxicity: Two case reports. Therapie 2021. PubMed
  209. Kajita N, Miyama S, Kinoshita K, Yoshida K, Narita M. Green tea-induced anaphylaxis: The first pediatric case report. Allergol Int 2021;70(4):507-508. PubMed
  210. Zheng KH, Zhu K, Wactawski-Wende J, et al. Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative. Int J Cancer 2021;149(12):2032-2044. PubMed
  211. Wang S, Li X, Yang Y, et al. Does coffee, tea and caffeine consumption reduce the risk of incident breast cancer? A systematic review and network meta-analysis. Public Health Nutr 2021;24(18):6377-6389. PubMed
  212. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Saudi Med J 2021;42(2):151-160. PubMed
  213. Gleason JL, Sundaram R, Mitro SD, et al. Association of maternal caffeine consumption during pregnancy with child growth. JAMA Netw Open. 2022;5(10):e2239609. PubMed
  214. Seufferlein T, Ettrich TJ, Menzler S, et al. Green tea extract to prevent colorectal adenomas, results of a randomized, placebo-controlled clinical trial. Am J Gastroenterol 2022;117(6):884-894. PubMed
  215. Teramoto M, Yamagishi K, Muraki I, Tamakoshi A, Iso H. Coffee and green tea consumption and cardiovascular disease mortality among people with and without hypertension. J Am Heart Assoc 2023;12(2):e026477. PubMed
  216. Veerman GDM, van der Werff SC, Koolen SLW, et al. The influence of green tea extract on nintedanib's bioavailability in patients with pulmonary fibrosis. Biomed Pharmacother 2022;151:113101. PubMed
  217. Misaka S, Ono Y, Taudte RV, et al. Exposure of fexofenadine, but not pseudoephedrine, is markedly decreased by green tea extract in healthy volunteers. Clin Pharmacol Ther 2022;112(3):627-634. PubMed
  218. Zhao H, Zhu W, Zhao X, et al. Efficacy of epigallocatechin-3-gallate in preventing dermatitis in patients with breast cancer receiving postoperative radiotherapy: A double-blind, placebo-controlled, phase 2 randomized clinical trial. JAMA Dermatol 2022;15 PubMed
  219. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed

See these in context on the Green Tea monograph →

Acetyl-l-carnitine 22 references
  1. Thal LJ, Carta A, Clarke WR, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's Disease. Neurology 1996;47:705-11. PubMed
  2. Sano M, Bell K, Cote L, et al. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's Disease. Arch Neurol 1992;49:1137-41. PubMed
  3. Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's Disease. Neurology 1991;41:1726-32. PubMed
  4. Brooks JO 3rd, Yesavage JA, Carta A, Bravi D. Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. Int Psychoger 1998;10:193-203. PubMed
  5. Pettegrew JW, Klunk WE, Panchalingam K, et al. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging 1995;16:1-4. PubMed
  6. Rai G, Wright G, Scott L, et al. Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia. Curr Med Res Opin 1990;11:638-47. PubMed
  7. Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Meta
  8. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol 2003;18:61-71.. PubMed
  9. Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.
  10. Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database Syst Rev 2003;2:CD003158.. PubMed
  11. Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385. PubMed
  12. De Grandis D, Minardi C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D 2002;3:223-31. PubMed
  13. 12761 Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 2004;1033:158-67. PubMed
  14. Sima AAF, Calvani M, Mehra M, et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: An analysis of two randomized, placebo-controlled trials. Diabetes Care 2005;28:89-94.
  15. Youle, M. and Osio, M. A double-blind, parallel-group, placebo-controlled, multicentre study of acetyl L-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV.Med. 2007;8(4):241-250.
  16. Brennan BP, Jensen JE, Hudson JI, Coit CE, Beaulieu A, Pope HG Jr, Renshaw PF, Cohen BM. A placebo-controlled trial of acetyl-L-carnitine and a-lipoic acid in the treatment of bipolar depression. J Clin Psychopharmacol. 2013 Oct;33(5):627-35.
  17. Ledinek AH, Sajko MC, Rot U. Evaluating the effects of amantadin, modafinil and acetyl-L-carnitine on fatigue in multiple sclerosis--result of a pilot randomized, blind study. Clin Neurol Neurosurg. 2013 Dec;115 Suppl 1:S86-9. PubMed
  18. Martinotti G, Andreoli S, Reina D, Di Nicola M, Ortolani I, Tedeschi D, Fanella F, Pozzi G, Iannoni E, D'Iddio S, Prof LJ. Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects. Prog Neuropsychop PubMed
  19. Baek SM, Zheng R, Seo EJ, Hwang DY, Kim BH. Pharmacokinetic comparisons of two acetyl-L-carnitine formulations in healthy Korean volunteers. Int J Clin Pharmacol Ther. 2015;53(11):980-6. PubMed
  20. Goodison G, Overeem K, de Monte V, Siskind D. Mania associated with self-prescribed acetyl-l-carnitine in a man with bipolar I disorder. Australas Psychiatry. 2017;25(1):13-4.
  21. Bruno A, Pandolfo G, Crucitti M, Lorusso S, Zoccali RA, Muscatello MR. Acetyl-L-Carnitine Augmentation of Clozapine in Partial-Responder Schizophrenia: A 12-Week, Open-Label Uncontrolled Preliminary Study. Clin Neuropharmacol. 2016;39(6):277-80. PubMed
  22. Veronese N, Stubbs B, Solmi M, Ajnakina O, Carvalho AF, Maggi S. Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis. Psychosom Med. 2018;80(2):154-9. PubMed

See these in context on the Acetyl-l-carnitine monograph →

Alpha-lipoic Acid 48 references
  1. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  2. Anon. Alpha-lipoic acid. Altern Med Rev 1998;3:308-10.
  3. Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with Type 2 diabetes. Diabetes Care 1999;22:280-7. PubMed
  4. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid: A 3-week, multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995;38:1425-33.
  5. Gleiter CH, Schreeb KH, Freudenthaler S, et al. Lack of interaction between thioctic acid, glibenclamide and acarbose. Br J Clin Pharmacol 1999;48:819-25. PubMed
  6. Jacob S, Henriksen EJ, Tritschler HJ, et al. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabet 1996;104:284-8. PubMed
  7. Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45:872-4.
  8. Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled, pilot trial. Free Rad Biol Med 1999;27:309-14.
  9. Segermann J, Hotze A, Ulrich H, Rao GS. Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels. Arzneimittelforschung 1991;41:1294-8.
  10. Beitner H. Randomized, placebo controlled, double-blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoaging of facial skin. Br J Dermatol 2003;149:841-9.
  11. Ziegler D, Nowak H, Kempler P, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A meta-analysis. Diabet Med 2004;21:114-21.
  12. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  13. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  14. Vincent HK, Bourguignon CM, Vincent KR, Taylor AG. Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. J Alt Complement Med 2007;13:577-84. PubMed
  15. Furukawa N, Miyamura N, Nishida K, et al. Possible relevance of alpha lipoic acid contained in a health supplement in a case of insulin autoimmune syndrome. Diabetes Res Clin Pract 2007;75:366-7. PubMed
  16. Ziegler D., Ametov A., Barinov A., Dyck P. J., Gurieva I., Low P. A., Munzel U., Yakhno N., Raz I., Novosadova M., Maus J., Samigullin, R. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Car
  17. Gu X. M., Zhang S. S., Wu J. C., Tang Z. Y., Lu Z. Q., Li H., Liu C., Chen L., Ning, G. [Efficacy and safety of high-dose a-lipoic acid in the treatment of diabetic polyneuropathy]. Zhonghua Yi Xue Za Zhi 2010;90(35):2473-2476.
  18. Porasuphatana S., Suddee S., Nartnampong A., Konsil J., Harnwong B., Santaweesuk A. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled
  19. Ansar H., Mazloom Z., Kazemi F., Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J 2011;32(6):584-588. DOI
  20. de Oliveira A. M., Rondó P. H., Luzia L. A., D'Abronzo F. H., Illison V. K. The effects of lipoic acid and a-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, pla
  21. Mazloom Z., Ansar H. The Effect of Alpha-Lipoic Acid on Blood Pressure in Type 2 Diabetics. Iranian Journal of Endocrinology and Metabolism 2009;11(3):245-250.
  22. Volchegorskii I. A., Rassokhina L. M., Koliadich M. I., Alekseev M. I. [Comparative study of alpha-lipoic acid and mexidol effects on affective status, cognitive functions and quality of life in diabetes mellitus patients]. Eksp Klin Farmakol 2011;74(11):
  23. Cavalcanti D. R., da Silveira F. R. Alpha lipoic acid in burning mouth syndrome--a randomized double-blind placebo-controlled trial. J Oral Pathol Med 2009;38(3):254-261. PubMed
  24. Koh E. H., Lee W. J., Lee S. A., Kim E. H., Cho E. H., Jeong E., Kim D. W., Kim M. S., Park J. Y., Park K. G., Lee H. J., Lee I. K., Lim S., Jang H. C., Lee K. H., Lee K. U. Effects of alpha-lipoic Acid on body weight in obese subjects. Am J Med 2011;124( PubMed
  25. Bergqvist-Karlsson, A., Thelin, I., and Bergendorff, O. Contact dermatitis to alpha-lipoic acid in an anti-wrinkle cream. Contact Dermatitis 2006;55(1):56-57.
  26. Tang, J., Wingerchuk, D. M., Crum, B. A., Rubin, D. I., and Demaerschalk, B. M. Alpha-lipoic acid may improve symptomatic diabetic polyneuropathy. Neurologist. 2007;13(3):164-167. PubMed
  27. Hegazy SK, Tolba OA, Mostafa TM, Eid MA, El-Afify DR. Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes. Rev Diabet Stud 2013;10(1):58-67. PubMed
  28. Huang Z, Wan X, Liu J, et al. Short-term continuous subcutaneous insulin infusion combined with insulin sensitizers rosiglitazone, metformin, or antioxidant a-lipoic acid in patients with newly diagnosed type 2 diabetes mellitus. Diabetes Technol Ther 201
  29. Sarezky D, Raquib AR, Dunaief JL, Kim BJ. Tolerability in the elderly population of high-dose alpha lipoic acid: a potential antioxidant therapy for the eye. Clin Ophthalmol. 2016 Sep 29;10:1899-1903. PubMed
  30. Boriani F, Granchi D, Roatti G, Merlini L, Sabattini T, Baldini N. Alpha-lipoic acid after median nerve decompression at the carpal tunnel: a randomized controlled trial. J Hand Surg Am. 2017 Apr;42(4):236-42. PubMed
  31. Karkabounas S, Papadopoulos N, Anastasiadou C, et al. Effects of a-lipoic Acid, carnosine, and thiamine supplementation in obese patients with type 2 diabetes mellitus: A randomized, double-blind study. J Med Food. 2018;21(12):1197-1203.
  32. Murray GL, Colombo J. (r)Alpha lipoic acid is a safe, effective pharmacologic therapy of chronic orthostatic hypotension associated with low sympathetic tone. Int J Angiol. 2019;28(3):188-193. PubMed
  33. Bobe G, Michels AJ, Zhang WJ, et al. A randomized controlled trial of long-term (R)-&alpha;-lipoic acid supplementation promotes weight loss in overweight or obese adults without altering baseline elevated plasma triglyceride concentrations. J Nutr. 2020:
  34. Passiatore M, Perna A, De-Vitis R, Taccardo G. The use of alfa-lipoic acid-R (ALA-R) in patients with mild-moderate carpal tunnel syndrome: A randomised controlled open label prospective study. Malays Orthop J. 2020;14(1):1-6. PubMed
  35. El-Nahas MR, Elkannishy G, Abdelhafez H, Elkhamisy ET, El-Sehrawy AA. Oral alpha lipoic acid treatment for symptomatic diabetic peripheral neuropathy: A randomized double-blinded placebo-controlled study. Endocr Metab Immune Disord Drug Targets. 2020. PubMed
  36. Kim BJ, Hunter A, Brucker AJ, et al. Orally administered alpha lipoic acid as a treatment for geographic atrophy: A randomized clinical trial. Ophthalmol Retina. 2020;4(9):889-898. PubMed
  37. Derosa G, D'Angelo A, Preti P, Maffioli P. Safety and efficacy of alpha lipoic acid during 4 years of observation: A retrospective, clinical trial in healthy subjects in primary prevention. Drug Des Devel Ther. 2020;14:5367-5374.
  38. Sun Y, Guan X, Wang H, et al. Randomized clinical trial of combined therapy with oral a-lipoic acid and NB-UVB for nonsegmental stable vitiligo. Dermatol Ther. 2021;34(1):e14610.
  39. Gilron I, Robb S, Tu D, et al. Double-blind, randomized, placebo-controlled crossover trial of alpha-lipoic acid for the treatment of fibromyalgia pain: the IMPALA trial. Pain. 2021;162(2):561-568. PubMed
  40. Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R. Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking a-lipoic acid. Clin Endocrinol (Oxf). 2014;81(2):204-9.
  41. Yukina M, Nuralieva N, Solovyev M, Troshina E, Vasilyev E. Insulin autoimmune syndrome. Endocrinol Diabetes Metab Case Rep. 2020;2020:19-0159. PubMed
  42. Moffa S, Improta I, Rocchetti S, Mezza T, Giaccari A. Potential cause-effect relationship between insulin autoimmune syndrome and alpha lipoic acid: Two case reports. Nutrition. 2019;57:1-4. PubMed
  43. Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking a-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313X18819601.
  44. EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, et al. Scientific opinion on the relationship between intake of alpha-lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome. EFSA J 2021;19(6):e06577. PubMed
  45. Jibril AT, Jayedi A, Shab-Bidar S. Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose-response meta-analysis of randomized trials. Endocr Connect 2022;11(10):e220322. PubMed
  46. Corazza M, Arlotti E, Schettini N, Pacetti L, Bianchi A, Borghi A. Allergic contact dermatitis due to a-lipoic acid in a topical over-the-counter product: A case report. Contact Dermatitis 2023.
  47. Velasco-Amador JP, Prados-Carmona Á, Navarro-Triviño FJ. Contact urticaria syndrome caused by alpha-lipoic acid in a master formula for vulvar lichen sclerosus. Contact Dermatitis 2023;89(2):136-137. PubMed
  48. Sehgal T, Ohri U, Mittal N, Attri P, Dishant F. A Case of Insulin Autoimmune Syndrome in an Indian Male Taking Alpha-Lipoic Acid. Cureus 2023;15(8):e43743. PubMed

See these in context on the Alpha-lipoic Acid monograph →

Riboflavin 5 references
  1. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-70. PubMed
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Leeson LJ, Weidenheimer JF. Stability of tetracycline and riboflavin. J Pharm Sci. 1969;58(3):355-7. PubMed
  4. MacLennan, S. C., Wade, F. M., Forrest, K. M., Ratanayake, P. D., Fagan, E., and Antony, J. High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. J Child Neurol. 2008;23(11):1300-1304.
  5. Dietary reference intakes (DRIs): estimated average requirements. Food and Nutrition Board, Institute of Medicine, National Academics. https://www.nal.usda.gov/sites/default/files/fnic_uploads//recommended_intakes_individuals.pdf Accessed July 24, 2017.

See these in context on the Riboflavin monograph →

Passion Flower 19 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  3. Fisher AA, Purcell P, Le Couteur DG. Toxicity of Passiflora incarnata L. J Toxicol Clin Toxicol 2000;38:63-6.
  4. Akhondzadeh S, Naghavi HR, Shayeganpour A, et al. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther 2001;26:363-7. PubMed
  5. Farnsworth N, Bingel A, Cordell G, et al. Potential value of plants as sources of new antifertility agents I. J Pharm Sci 1975;64:535-98. DOI
  6. Mori A, Hasegawa K, Murasaki M, et al. Clinical evaluation of Passiflamin (passiflora extract) on neurosis - multicenter double blind study in comparison with mexazolam. Rinsho Hyoka (Clinical Evaluation) 1993;21:383-440.
  7. Miyasaka LS, Atallah AN, Soares BG. Passiflora for anxiety disorder. Cochrane Database Syst Rev 2007;(1):CD004518. DOI
  8. Speroni E., Minghetti A. Neuropharmacological activity of extracts from Passiflora incarnata. Planta Med. 1988;54:488-91.
  9. Capasso A., Sorrentino L. Pharmacological studies on the sedative and hypnotic effect of Kava kava and Passiflora extracts combination. Phytomedicine. 2005;12:39-45. PubMed
  10. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009 Dec;23:1795-6.
  11. Smith, G. W., Chalmers, T. M., and Nuki, G. Vasculitis associated with herbal preparation containing Passiflora extract. Br J Rheumatol. 1993;32(1):87-88.
  12. Soulimani, R., Younos, C., Jarmouni, S., Bousta, D., Misslin, R., and Mortier, F. Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol. 1997;57(1):11-20. PubMed
  13. Nojoumi M, Ghaeli P, Salimi S, Sharifi A, Raisi F. Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients ?with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study. Iran J Psychiatry. 2016;1
  14. Rokhtabnak F, Ghodraty MR, Kholdebarin A, et al. Comparing the Effect of Preoperative Administration of Melatonin and Passiflora incarnata on Postoperative Cognitive Disorders in Adult Patients Undergoing Elective Surgery. Anesth Pain Med. 2016;7(1):e4123 PubMed
  15. Dantas LP, de Oliveira-Ribeiro A, de Almeida-Souza LM, Groppo FC. Effects of passiflora incarnata and midazolam for control of anxiety in patients undergoing dental extraction. Med Oral Patol Oral Cir Bucal. 2017;22(1):e95-e101. PubMed
  16. Ozturk Z, Kalayci CC. Pregnancy outcomes in psychiatric patients treated with passiflora incarnata. Complement Ther Med. 2018 Feb;36:30-32. PubMed
  17. da Cunha RS, Amorim KS, Gercina AC, et al. Herbal medicines as anxiolytics prior to third molar surgical extraction. A randomized controlled clinical trial. Clin Oral Investig. 2020. PubMed
  18. Schäfer AM, Gilgen PM, Spirgi C, et al. Constituents of Passiflora incarnata, but Not of Valeriana officinalis, Interact with the Organic Anion Transporting Polypeptides (OATP)2B1 and OATP1A2. Planta Med. 2021. PubMed
  19. Mazzari ALDA, Lacerda MG, Milton FA, et al. In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity. Front Pharmacol 2022;13:826395. PubMed

See these in context on the Passion Flower monograph →

Eleuthero 24 references
  1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  2. McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. CMAJ 1996;155:293-5.
  3. Awang DVC. Siberian ginseng toxicity may be case of mistaken identity (letter). CMAJ 1996;155:1237.
  4. Mills S, Bone K. Principles and Practice of Phytotherapy. London: Churchill Livingstone, 2000.
  5. Harkey MR, Henderson GL, Zhou L, et al. Effects of Siberian ginseng (Eleutherococcus senticosus) on c-DNA-expressed P450 drug metabolizing enzymes. Alt Ther 2001;7:S14.
  6. Hikino H, Takahashi M, Otake K, Konno C. Isolation and hypoglycemic activity of eleutherans A, B, C, D, E, F, and G: glycans of Eleutherococcus senticosus roots. J Nat Prod 1986;49:293-7. PubMed
  7. Yun-Choi HS, Kim JH, Lee JR. Potential inhibitors of platelet aggregation from plant sources, III. J Nat Prod 1987;50:1059-64. PubMed
  8. Donovan JL, DeVane CL, Chavin KD, et al. Siberian Ginseng (Eleutheroccus senticosus) Effects on CYP2D6 and CYP3A4 Activity in Normal Volunteers. Drug Metab Dispos 2003;31:519-22.. PubMed
  9. Hartz AJ, Bentler S, Noyes R et al. Randomized controlled trial of Siberian ginseng for chronic fatigue. Psychol Med 2004;34:51-61. PubMed
  10. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: the role of ginsenosides. J Am Coll Nutr 2004;23:248-58. PubMed
  11. Dasgupta A, Wu S, Actor J, et al. Effect of Asian and Siberian ginseng on serum digoxin measurement by five digoxin immunoassays. Significant variation in digoxin-like immunoreactivity among commercial ginsengs. Am J Clin Pathol 2003;119:298-303. DOI
  12. Takahashi T, Kaku T, Sato T, et al. Effects of Acanthopanax senticosus HARMS extract on drug transport in human intestinal cell line Caco-2. J Nat Med. 2010;64(1):55-62. PubMed
  13. Fuchikami H, Satoh H, Tsujimoto M, Ohdo S, Ohtani H, Sawada Y. Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 2006;34:577-82. PubMed
  14. Friedman, J. A., Taylor, S. A., McDermott, W., and Alikhani, P. Multifocal and recurrent subarachnoid hemorrhage due to an herbal supplement containing natural coumarins. Neurocrit.Care 2007;7(1):76-80. PubMed
  15. Molokovskii, D. S., Davydov, V. V., and Tiulenev, V. V. [The action of adaptogenic plant preparations in experimental alloxan diabetes]. Probl.Endokrinol.(Mosk) 1989;35(6):82-87.
  16. Schmolz, M. W., Sacher, F., and Aicher, B. The synthesis of Rantes, G-CSF, IL-4, IL-5, IL-6, IL-12 and IL-13 in human whole-blood cultures is modulated by an extract from Eleutherococcus senticosus L. roots. Phytother.Res 2001;15(3):268-270.
  17. Huang, D. B., Ran, R. Z., and Yu, Z. F. [Effect of Acanthopanax senticosus injection on the activities of human tumor necrosis factor and natural killer cell in blood in the patients with lung cancer]. Zhongguo Zhong.Yao Za Zhi. 2005;30(8):621-624.
  18. Niu, H. S., Hsu, F. L., Liu, I. M., and Cheng, J. T. Increase of beta-endorphin secretion by syringin, an active principle of Eleutherococcus senticosus, to produce antihyperglycemic action in type 1-like diabetic rats. Horm.Metab Res 2007;39(12):894-898
  19. Watanabe, K., Kamata, K., Sato, J., and Takahashi, T. Fundamental studies on the inhibitory action of Acanthopanax senticosus Harms on glucose absorption. J Ethnopharmacol. 10-28-2010;132(1):193-199. PubMed
  20. Bazaz'ian, G. G., Liapina, L. A., Pastorova, V. E., and Zvereva, E. G. [Effect of Eleutherococcus on the functional status of the anticoagulation system in older animals]. Fiziol.Zh.SSSR Im I.M.Sechenova 1987;73(10):1390-1395.
  21. Kaloeva, Z. D. [Effect of the glycosides of Eleutherococcus senticosus on the hemodynamic indices of children with hypotensive states]. Farmakol.Toksikol. 1986;49(5):73.
  22. Martinez, B. and Staba, E. J. The physiological effects of Aralia, Panax and Eleutherococcus on exercised rats. Jpn J Pharmacol 1984;35(2):79-85. DOI
  23. Medon, P. J., Thompson, E. B., and Farnsworth, N. R. Hypoglycemic effect and toxicity of Eleutherococcus senticosus following acute and chronic administration in mice. Zhongguo Yao Li Xue.Bao. 1981;2(4):281-285.
  24. Freye E, GLeske J. Siberian ginseng results in beneficial effects on glucose metabolism in diabetes type 2 patients: a double blind placebo-controlled study in comparison to panax ginseng. Int J Clin Nutr. 2013;1(1):11-17.

See these in context on the Eleuthero monograph →

Grape 34 references
  1. Kiesewetter H, Koscielny J, Kalus U, et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung
  2. Xiao Dong S, Zhi Ping Z, Zhong Xiao W, et al. Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 1999;48:638-40. PubMed
  3. Vaswani SK, Hamilton RG, Carey RN, et al. Anaphylaxis recurrent urticaria and angioedema from grape hypersensitivity. J Allergy Clin Immunol 1998;101:S31.
  4. Chevallier A. The Encyclopedia of Medicinal Plants. London, UK: Dorling Kindersley, Ltd., 1996.
  5. Bernstein DI, Bernstein CK, Deng C, et al. Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study. Ann Allergy Asthma Immunol 2002;88:272-8.. PubMed
  6. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33. PubMed
  7. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  8. Ray, S. D., Parikh, H., Hickey, E., Bagchi, M., and Bagchi, D. Differential effects of IH636 grape seed proanthocyanidin extract and a DNA repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent aniline hydroxylation. Mol Cell B PubMed
  9. O'Byrne, D. J., Devaraj, S., Grundy, S. M., and Jialal, I. Comparison of the antioxidant effects of Concord grape juice flavonoids alpha-tocopherol on markers of oxidative stress in healthy adults. Am J Clin.Nutr. 2002;76(6):1367-1374.
  10. Schaefer, E., Peil, H., Ambrosetti, L., and Petrini, O. Oedema protective properties of the red vine leaf extract AS 195 (Folia vitis viniferae) in the treatment of chronic venous insufficiency. A 6-week observational clinical trial. Arzneimittelforschun PubMed
  11. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  12. de Lange, D. W., Scholman, W. L., Kraaijenhagen, R. J., Akkerman, J. W., and van de Wiel, A. Alcohol and polyphenolic grape extract inhibit platelet adhesion in flowing blood. Eur.J Clin.Invest 2004;34(12):818-824. PubMed
  13. Samet, J. M. and Coultas, D. B. Reduced forced vital capacity in California grape workers. What does it mean? Am Rev.Respir.Dis 1992;145(2 Pt 1):255-256. PubMed
  14. Gamsky, T. E., McCurdy, S. A., Samuels, S. J., and Schenker, M. B. Reduced FVC among California grape workers. Am Rev.Respir.Dis 1992;145(2 Pt 1):257-262. PubMed
  15. de Lange, D. W., Verhoef, S., Gorter, G., Kraaijenhagen, R. J., van de Wiel, A., and Akkerman, J. W. Polyphenolic grape extract inhibits platelet activation through PECAM-1: an explanation for the French paradox. Alcohol Clin.Exp.Res 2007;31(8):1308-1314 PubMed
  16. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu
  17. Krikorian, R., Nash, T. A., Shidler, M. D., Shukitt-Hale, B., and Joseph, J. A. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103(5):730-734. PubMed
  18. Ingersoll, G. L., Wasilewski, A., Haller, M., Pandya, K., Bennett, J., He, H., Hoffmire, C., and Berry, C. Effect of concord grape juice on chemotherapy-induced nausea and vomiting: results of a pilot study. Oncol.Nurs.Forum 2010;37(2):213-221. PubMed
  19. Oliveira-Freitas, V. L., Dalla, Costa T., Manfro, R. C., Cruz, L. B., and Schwartsmann, G. Influence of purple grape juice in cyclosporine bioavailability. J Ren Nutr. 2010;20(5):309-313. PubMed
  20. Hollis, J. H., Houchins, J. A., Blumberg, J. B., and Mattes, R. D. Effects of concord grape juice on appetite, diet, body weight, lipid profile, and antioxidant status of adults. J Am Coll.Nutr. 2009;28(5):574-582. PubMed
  21. Dohadwala, M. M., Hamburg, N. M., Holbrook, M., Kim, B. H., Duess, M. A., Levit, A., Titas, M., Chung, W. B., Vincent, F. B., Caiano, T. L., Frame, A. A., Keaney, J. F., Jr., and Vita, J. A. Effects of Concord grape juice on ambulatory blood pressure in
  22. Rabe, E., Stucker, M., Esperester, A., Schafer, E., and Ottillinger, B. Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study. Eur.J Vasc.Endovasc. PubMed
  23. Trotta, M., Cesaretti, M., Conzi, R., Derchi, L. E., and Borgonovo, G. Elderly male with mesogastric pain. Small bowel obstruction caused by an intact fresh grape. Ann.Emerg.Med 2011;58(4):e1-e2. PubMed
  24. McCurdy, S. A., Wiggins, P., Schenker, M. B., Munn, S., Shaieb, A. M., Weinbaum, Z., Goldsmith, D., McGillis, S. T., Berman, B., and Samuels, S. Assessing dermatitis in epidemiologic studies: occupational skin disease among California grape and tomato ha
  25. Winter, C. K. and Kurtz, P. H. Factors influencing grape worker susceptibility to skin rashes. Bull.Environ.Contam Toxicol. 1985;35(3):418-426. PubMed
  26. Yamasaki, R., Dekio, S., and Jidoi, J. Contact dermatitis from grape bud. Contact Dermatitis 1985;12(4):226-227. PubMed
  27. Cox, J. and Grigg, M. Small bowel obstruction by an intact grape. J Am Geriatr.Soc 1986;34(7):550. PubMed
  28. Faircloth, D. E. and Robison, W. J. Obstruction of the sigmoid colon by grape seeds. JAMA 11-27-1981;246(21):2430. PubMed
  29. Marguerie, C. and Drouet, M. [Occupational eosinophilic lung in a grape grower: role of sulfites]. Allerg.Immunol.(Paris) 1995;27(5):163-167.
  30. Brito, FF., Martinez, A., Palacios, R., Mur, P., Gomez, E., Galindo, P. A., Borja, J., and Martinez, J. Rhinoconjunctivitis and asthma caused by vine pollen: a case report. J Allergy Clin Immunol 1999;103(2 Pt 1):262-266. PubMed
  31. Ras RT, Zock PL, Zebregs YE, et al. Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension. Br J Nutr 2013;110(12):2234-41. PubMed
  32. Berry AC, Nakshabendi R, Abidali H, et al. Adverse effects of grape seed extract supplement: A clinical case and long-term follow-up. J Diet Suppl. 2016;13(2):232-5. PubMed
  33. Martínez-Maqueda D, Zapatera B, Gallego-Narbón A, Vaquero MP, Saura-Calixto F, Pérez-Jiménez J. A 6-week supplementation with grape pomace to subjects at cardiometabolic risk ameliorates insulin sensitivity, without affecting other metabolic syndrome mark
  34. Moon SW, Shin YU, Cho H, Bae SH, Kim HK; and for the Mogen Study Group. Effect of grape seed proanthocyanidin extract on hard exudates in patients with non-proliferative diabetic retinopathy. Medicine (Baltimore) 2019;98(21):e15515. PubMed

See these in context on the Grape monograph →

Schisandra 26 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Iwata H, Tezuka Y, Kadota S, et al. Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos 2004;32:1351-8. PubMed
  3. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  4. Xin HW, Wu XC, Li Q, et al. Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers. Br J Clin Pharmacol 2007;64:469-75.
  5. Qin XL, Bi HC, Wang XD, et al. Mechanistic understanding of the different effects of Wuhzi Tablet (Schisandra sphenanthera extract) on the absorption and first-pass intestinal and hepatic metabolism of tacrolimus (FK506). Int J Pharm 2010;389:114-21.
  6. Makino, T., Mizuno, F., and Mizukami, H. Does a kampo medicine containing schisandra fruit affect pharmacokinetics of nifedipine like grapefruit juice? Biol.Pharm.Bull. 2006;29(10):2065-2069. PubMed
  7. Fan L, Mao XQ, Tao GY, Wang G, Jiang F, Chen Y, Li Q, Zhang W, Lei HP, Hu DL, Huang YF, Wang D, Zhou HH. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica. 2009 Mar;39(
  8. Jiang W, Wang X, Xu X, Kong L. Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients. Int J Clin Pharmacol Ther. 2010 Mar;48(3):224-9. PubMed
  9. Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009 May;67(5):541-6.
  10. Li J, Chen S, Qin X, et at. Wuzhi Tablet (<i>Schisandra sphenanthera</i> Extract) is a Promising Tacrolimus-Sparing Agent for Renal Transplant Recipients Who are CYP3A5 Expressers: a Two-Phase Prospective Study. Drug Metab Dispos. 2017;45(11):1114-1119.
  11. Qin XL, Li JL, Wang SH, Chen X, Huang M, Bi HC. Co-administration of Wuzhi tablet (Schisandra sphenanthera extract) alters tacrolimus pharmacokinetics in a dose- and time-dependent manner in rats. J Ethnopharmacol. 2020;263:113233. PubMed
  12. Yuan F, Liang X, Chen X, Qin X, Tan C, Wang L. CYP2C19 is involved in the effect of Wuzhi tablet (Schisandra sphenanthera extract) and its constituents on the pharmacokinetics of intravenous voriconazole. Pharmazie. 2020;75(11):559-564. DOI
  13. Zhang Z, Lu X, Dong L, Ma J, Fan X. Clinical observation on the effect of Wuzhi soft capsule on FK506 concentration in membranous nephropathy patients. Medicine (Baltimore). 2019;98(48):e18150. PubMed
  14. Yoo HH, Lee M, Lee MW, Lim SY, Shin J, Kim DH. Effects of Schisandra lignans on P-glycoprotein-mediated drug efflux in human intestinal Caco-2. Planta Med. 2007;73(5):444-50.
  15. Qiangrong P, Wang T, Lu Q, Hu X. Schisandrin B--a novel inhibitor of P-glycoprotein. Biochem Biophys Res Commun. 2005;335(2):406-11. PubMed
  16. Chen L, Ji N, Zhang M, Chen W. The influence of Wuzhi capsule on the pharmacokinetics of cyclophosphamide. Recent Pat Anticancer Drug Discov 2021. PubMed
  17. Cheng X, Ma J, Xu X, Zhang L, Wang X, Wu R. Effect of Wuzhi capsules on cyclosporine A concentration in children with aplastic anemia immunotherapy: a single-center observational study. Expert Rev Clin Pharmacol 2022:1-5. PubMed
  18. Cheng F, Li Q, Wang J, Zeng F, Zhang Y. Effects and safety evaluation of Wuzhi capsules combined with tacrolimus for the treatment of kidney transplantation recipients. J Clin Pharm Ther 2021;46(6):1636-49. PubMed
  19. Teng F, Wang W, Zhang W, et al. Effect of hepar-protecting Wuzhi capsule on pharmacokinetics and dose-effect character of tacrolimus in healthy volunteers. Biopharm Drug Dispos 2022.
  20. Kou K, Sun X, Li M, et al. Beneficial effects of Wuzhi capsule on tacrolimus blood concentrations in liver transplant patients with different donor-recipient CYP3A5 genotypes. J Clin Pharm Ther 2022;47(2):200-10. PubMed
  21. Peng Y, Jiang F, Zhou R, et al. Clinical evaluation of the efficacy and safety of co-administration of Wuzhi capsule and tacrolimus in adult Chinese patients with myasthenia gravis. Neuropsychiatr Dis Treat 2021;17:2281-9. PubMed
  22. Chen P, Dai R, She Y, et al. Prediction of tacrolimus and Wuzhi tablet pharmacokinetic interaction magnitude in renal transplant recipients. Clin Transplant 2022;36(12):e14807. PubMed
  23. Qu J, Bian R, Liu B, et al. The pharmacokinetic study of tacrolimus and Wuzhi capsule in Chinese liver transplant patients. Front Pharmacol 2022;13:956166. PubMed
  24. Zhou Y, Huang X, Liu L, et al. Effect of Wuzhi preparations on tacrolimus in CYP3A5 expressers during the early period after transplantation: A real-life experience from heart transplant recipients. Transpl Immunol 2023;76:101748. PubMed
  25. Huang Q, Lin X, Wang Y, et al. Tacrolimus pharmacokinetics in pediatric nephrotic syndrome: A combination of population pharmacokinetic modelling and machine learning approaches to improve individual prediction. Front Pharmacol 2022;13:942129. PubMed
  26. Wang CB, Zhang YJ, Zhao MM, Zhao LM. Population pharmacokinetic analyses of tacrolimus in non-transplant patients: a systematic review. Eur J Clin Pharmacol 2023;79(7):897-913. PubMed

See these in context on the Schisandra monograph →

Molybdenum 8 references
  1. Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med 1998;18:673-85. DOI
  2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  3. Rajagopalan KV. Molybdenum: an essential trace element in human nutrition. Annu Rev Nutr 1988;8:401-27. PubMed
  4. Selden AI, Berg NP, Soderbergh A, Bergstrom BE. Occupational molybdenum exposure and a gouty electrician. Occup Med (Lond) 2005;55:145-8. PubMed
  5. Al-Saleh E, Nandakumaran M, Al-Shammari M, Al-Harouny A. Maternal-fetal status of copper, iron, molybdenum, selenium and zinc in patients with gestational diabetes. J Matern Fetal Neonatal Med 2004;16:15-21. PubMed
  6. Koster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000;356:1895-7. PubMed
  7. Vyskocil A, Viau C. Assessment of molybdenum toxicity in humans. J Appl Toxicol 1999;19:185-92. DOI
  8. Momcilovic, B. A case report of acute human molybdenum toxicity from a dietary molybdenum supplement--a new member of the "Lucor metallicum" family. Arh.Hig.Rada Toksikol. 1999;50(3):289-297. DOI

See these in context on the Molybdenum monograph →

Niacin 66 references
  1. Garg R, Malinow MR, Pettinger M, et al. Niacin treatment increases plasma homocysteine levels. Am Heart J 1999;138:1082-7.
  2. Anon. Inositol hexaniacinate. Altern Med Rev 1998;3:222-3.
  3. Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32. PubMed
  4. Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group. Arch Intern Med 2000;160:1177-84. PubMed
  5. Gibbons LW, Gonzalez V, Gordon N, Grundy S. The prevalence of side effects with regular and sustained-release nicotinic acid. Am J Med 1995;99:378-85. PubMed
  6. Whelan AM, Price SO, Fowler SF, Hainer BL. The effect of aspirin on niacin-induced cutaneous reactions. J Fam Pract 1992;34:165-8.
  7. Jungnickel PW, Maloley PA, Vander Tuin EL, et al. Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions. J Gen Intern Med 1997;12:591-6. PubMed
  8. Capuzzi DM, Guyton JR, Morgan JM, et al. Efficacy and safety of an extended-release niacin (Niaspan): a long-term study. Am J Cardiol 1998;82:74-81;disc. 85U-6U. PubMed
  9. Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252-8. PubMed
  10. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271:672-7. DOI
  11. Knopp RH, Alagona P, Davidson M, et al. Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Metabolism 1998;47:1097-104. PubMed
  12. Knopp RH. Clinical profiles of plain versus sustained-release niacin (Niaspan) and the physiologic rationale for nighttime dosing. Am J Cardiol 1998;82:24U-28U;discussion 39U-41U. PubMed
  13. Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 1990;264:723-6. DOI
  14. Leighton RF, Gordon NF, Small GS, et al. Dental and gingival pain as side effects of niacin therapy. Chest 1998;114:1472-4. PubMed
  15. American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9. DOI
  16. Vega GL, Grundy SM. Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Arch Intern Med 1994;154:73-82. DOI
  17. Guyton JR, Goldberg AC, Kreisberg RA, et al. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol 1998;82:737-43.
  18. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  19. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  20. Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71. PubMed
  21. Rader JI, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992;92:77-81. PubMed
  22. Kahn SE, Beard JC, Schwartz MW, et al. Increased B-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. Diabetes 1989;38:562-8.
  23. Schwartz ML. Severe reversible hyperglycemia as a consequence of niacin therapy. Arch Int Med 1993;153:2050-2. DOI
  24. Raising HDL and Niacin Use. Pharmacist's Letter/Prescriber's Letter 2004;20(5):200504.
  25. McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705. PubMed
  26. Reaven P, Witztum JL. Lovastatin, nicotinic acid and rhabdomyolysis (letter). Ann Int Med 1988;109:597-8. PubMed
  27. Ito MK. Advances in the understanding and management of dyslipidemia: using niacin-based therapies. Am J Health-Syst Pharm 2003;60(suppl 2):s15-21. PubMed
  28. Schwab RA, Bachhuber BH. Delirium and lactic acidosis caused by ethanol and niacin coingestion. Am J Emerg Med 1991;9:363-5. PubMed
  29. Product information: Niaspan. Kos Pharmaceuticals. Cranbury, NJ. 2005. Available at www.niaspan.com/professional/content/pdfs/productinfo.pdf. (Accessed 3 March 2006).
  30. Ding RW, Kolbe K, Merz B, et al. Pharmacokinetics of nicotinic acid-salicylic acid interaction. Clin Pharmacol Ther 1989;46:642-7. PubMed
  31. NIH News. NIH stops clinical trial on combination cholesterol treatment. May 26, 2011. http://www.nih.gov/news/health/may2011/nhlbi-26.htm. (Accessed 3 June 2011).
  32. Dearing BD, Lavie CJ, Lohmann TP, Genton E. Niacin-induced clotting factor synthesis deficiency with coagulopathy. Arch Intern Med. 1992;152(4):861-3. DOI
  33. O'Brien T, Silverberg JD, Nguyen TT. Nicotinic acid-induced toxicity associated with cytopenia and decreased levels of thyroxine-binding globulin. Mayo Clin Proc. 1992;67(5):465-8. PubMed
  34. Gadegbeku CA, Dhandayuthapani A, Shrayyef MZ, Egan BM. Hemodynamic effects of nicotinic acid infusion in normotensive and hypertensive subjects. Am J Hypertens. 2003;16(1):67-71. PubMed
  35. Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health Syst Pharm. 1995;52(15):1639-45. PubMed
  36. Litin SC, Anderson CF. Nicotinic acid-associated myopathy: a report of three cases. Am J Med. 1989;86(4):481-3. PubMed
  37. Dunn RT, Ford MA, Rindone JP, Kwiecinski FA. Low-Dose Aspirin and Ibuprofen Reduce the Cutaneous Reactions Following Niacin Administration. Am J Ther. 1995;2(7):478-480. PubMed
  38. Cashin-Hemphill L, Spencer CA, Nicoloff JT, et al. Alterations in serum thyroid hormonal indices with colestipol-niacin therapy. Ann Intern Med. 1987;107(3):324-9. PubMed
  39. Drinka PJ. Alterations in thyroid and hepatic function tests associated with preparations of sustained-release niacin. Mayo Clin Proc. 1992;67(12):1206. PubMed
  40. Shakir KM, Kroll S, Aprill BS, Drake AJ 3rd, Eisold JF. Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state. Mayo Clin Proc. 1995;70(6):556-8. PubMed
  41. Etchason JA, Miller TD, Squires RW, et al. Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin. Mayo Clin Proc. 1991;66(1):23-8. PubMed
  42. Henkin Y, Johnson KC, Segrest JP. Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin. JAMA. 1990;264(2):241-3. DOI
  43. Henkin Y, Oberman A, Hurst DC, Segrest JP. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med. 1991;91(3):239-46. PubMed
  44. Brown BG, Bardsley J, Poulin D, et al. Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease. Am J Cardiol. 1997;80(2)
  45. Goldberg A, Alagona P Jr, Capuzzi DM, et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol. 2000;85(9):1100-5. PubMed
  46. Aronov DM, Keenan JM, Akhmedzhanov NM, et al. Clinical trial of wax-matrix sustained-release niacin in a Russian population with hypercholesterolemia. Arch Fam Med. 1996;5(10):567-75. PubMed
  47. Morgan JM, Capuzzi DM, Guyton JR, et al. Treatment Effect of Niaspan, a Controlled-release Niacin, in Patients With Hypercholesterolemia: A Placebo-controlled Trial. J Cardiovasc Pharmacol Ther. 1996;1(3):195-202. PubMed
  48. Andersson RG, Aberg G, Brattsand R, Ericsson E, Lundholm L. Studies on the mechanism of flush induced by nicotinic acid. Acta Pharmacol Toxicol (Copenh). 1977 Jul;41(1):1-10. PubMed
  49. Brown WV. Niacin for lipid disorders. Indications, effectiveness, and safety. Postgrad Med. 1995 Aug;98(2):185-9, 192-3. PubMed
  50. O'REILLY PO, CALLBECK MJ, HOFFER A. Sustained-release nicotinic acid (nicospan); effect on (1) cholesterol levels and (2) leukocytes. Can Med Assoc J. 1959;80(5):359-62.
  51. Gharavi AG, Diamond JA, Smith DA, Phillips RA. Niacin-induced myopathy. Am J Cardiol. 1994;74(8):841-2. PubMed
  52. Litin SC, Anderson CF. Nicotinic acid-associated myopathy: a report of three cases. Am J Med. 1989;86(4):481-3. PubMed
  53. Fraunfelder FW, Fraunfelder FT, Illingworth DR. Adverse ocular effects associated with niacin therapy. Br J Ophthalmol 1995;79:54-56. PubMed
  54. Ali EH, McJunkin B, Jubelirer S, Hood W. Niacin induced coagulopathy as a manifestation of occult liver injury. W V Med J. 2013 Jan-Feb;109(1):12-4
  55. Aramwit P, Srisawadwong R, Supasyndh O. Effectiveness and safety of extended-release nicotinic acid for reducing serum phosphorus in hemodialysis patients. J Nephrol. 2012 May-Jun;25(3):354-62. PubMed
  56. Bassan M. A case for immediate-release niacin. Heart Lung. 2012 Jan-Feb;41(1):95-8. PubMed
  57. Davidson MH, Rooney M, Pollock E, Drucker J, Choy Y. Effect of colesevelam and niacin on low-density lipoprotein cholesterol and glycemic control in subjects with dyslipidemia and impaired fasting glucose. J Clin Lipidol. 2013 Sep-Oct;7(5):423-32. PubMed
  58. Guyton JR, Fazio S, Adewale AJ, Jensen E, Tomassini JE, Shah A, Tershakovec AM. Effect of extended-release niacin on new-onset diabetes among hyperlipidemic patients treated with ezetimibe/simvastatin in a randomized controlled trial. Diabetes Care. 2012 PubMed
  59. Loebl T, Raskin S. A novel case report: acute manic psychotic episode after treatment with niacin. J Neuropsychiatry Clin Neurosci. 2013 Fall;25(4):E14. PubMed
  60. Teo KK, Goldstein LB, Chaitman BR, Grant S, Weintraub WS, Anderson DC, Sila CA, Cruz-Flores S, Padley RJ, Kostuk WJ, Boden WE; AIM-HIGH Investigators. Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the
  61. Goldie C, Taylor AJ, Nguyen P, McCoy C, Zhao XQ, Preiss D. Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomized controlled trials. Heart. 2016 Feb;102(3):198-203.
  62. Schandelmaier S, Briel M, Saccilotto R, Olu KK, Arpagaus A, Hemkens LG, Nordmann AJ. Niacin for primary and secondary prevention of cardiovascular events. Cochrane Database Syst Rev. 2017 Jun 14;6:CD009744. PubMed
  63. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018;71(22):2570-84. PubMed
  64. Song S, Lee CJ, Oh J, Park S, Kang SM, Lee SH. Effect of Niacin on Carotid Atherosclerosis in Patients at Low-Density Lipoprotein-Cholesterol Goal but High Lipoprotein (a) Level: a 2-Year Follow-Up Study. J Lipid Atheroscler. 2019;8(1):58-66. PubMed
  65. Kimura H, Umemori Y, Yuki D. Anaphylactic shock-like symptoms due to niacin overdose: A case report. J Dermatol 2022;49(8):e287-e288. PubMed
  66. Nawaz N, Mistretta T, Karime C, Lewis J, Wolf E. Cholestatic Drug-Induced Liver Injury in a Patient Taking High-Dose Niacin for Hyperlipidemia. J Investig Med High Impact Case Rep 2024;12:23247096231224349. PubMed

See these in context on the Niacin monograph →

Chromium 53 references
  1. Cerulli J, Grabe DW, Gauthier I, et al. Chromium picolinate toxicity. Ann Pharmacother 1998;32:428-31. PubMed
  2. Urberg M, Zemel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabolism 1987;36:896-9. PubMed
  3. Mohamedshah FY, Moser-Veillon PB, Yamini S, et al. Distribution of a stable isotope of chromium (53Cr) in serum, urine, and breast milk in lactating women. Am J Clin Nutr 1998;67:1250-5. PubMed
  4. Wasser WG, Feldman NS, D'Agati VD. Chronic renal failure after ingestion of over-the-counter chromium picolinate. [letter]. Ann Intern Med 1997;126:410. PubMed
  5. Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998;56:174-7. PubMed
  6. Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 1998;17:548-55. PubMed
  7. McLeod MN, Gaynes BN, Golden RN. Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients. J Clin Psych 1999;60:237-40. PubMed
  8. Fowler JF Jr. Systemic contact dermatitis caused by oral chromium picolinate. Cutis 2000;65:116. DOI
  9. Trent LK, Thieding-Cancel D. Effects of chromium picolinate on body composition. J Sports Med Phys Fitness 1995;35:273-80.
  10. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  11. Rabinovitz H, Friedensohn A, Leibovitz A, et al. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004;74:178-82. PubMed
  12. Lanca S, Alves A, Vieira AI, et al. Chromium-induced toxic hepatitis. Eur J Intern Med 2002;13:518-20. PubMed
  13. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  14. Davidson JR, Abraham K, Connor KM, McLeod MN. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53:261-4.. PubMed
  15. Food Standards Agency. Medicines and Healthcare products Regulatory Agency (MHRA). Expert Group on Vitamins and Minerals. Available at: http://cot.food.gov.uk/sites/default/files/vitmin2003.pdf.
  16. Mouser JF, Hak EB, Helms RA, et al. Chromium and zinc concentrations in pediatric patients receiving long-term parenteral nutrition. Am J Health Syst Pharm 1999;56:1950-6. PubMed
  17. Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med 2005;142:477-8. PubMed
  18. Wani S, Weskamp C, Marple J, Spry L. Acute tubular necrosis associated with chromium picolinate-containing dietary supplement. Ann Pharmacother 2006;40:563-6. PubMed
  19. Kleefstra N, Houweling ST, Jansman FG, et al. Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care 2006;29: PubMed
  20. Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006;29:1826-32. PubMed
  21. Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther 2006;8:636-43. PubMed
  22. John-Kalarickal J, Pearlman G, Carlson HE. New medications which decrease levothyroxine absorption. Thyroid 2007;17:763-5. PubMed
  23. Yazaki Y, Faridi Z, Ma Y, et al. A pilot study of chromium picolinate for weight loss. J Altern Complement Med 2010;16:291-9. PubMed
  24. Davis ML, Seaborn CD, and Stoecker BJ. Effects of over-the-counter drugs on chromium retention and urinary excretion in rats. Nutrition Research 1995;15(2):201-210.
  25. Young P, Turiansky G, Bonner M, and et al. Acute generalized exanthematous pustulosis induced by chromium picolinate. J.Am Acad.Dermatol. 1999;41(5 Pt 2):820-823. PubMed
  26. Gibb, H. J., Lees, P. S., Pinsky, P. F., and Rooney, B. C. Lung cancer among workers in chromium chemical production. Am J Ind.Med 2000;38(2):115-126. DOI
  27. Gibb, H. J., Lees, P. S., Pinsky, P. F., and Rooney, B. C. Clinical findings of irritation among chromium chemical production workers. Am J Ind.Med 2000;38(2):127-131. PubMed
  28. Pittler, M. H. and Ernst, E. Dietary supplements for body-weight reduction: a systematic review. Am.J.Clin Nutr. 2004;79(4):529-536. PubMed
  29. Pei, D., Hsieh, C. H., Hung, Y. J., Li, J. C., Lee, C. H., and Kuo, S. W. The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism 2 PubMed
  30. Hisatomi, K., Ishii, H., Hashiguchi, K., Seki, M., Ide, M., Sugiyama, K., Ishimoto, H., Nakayama, S., Mukae, H., and Kohno, S. Interstitial pneumonia caused by inhalation of fumes of nickel and chrome. Respirology. 2006;11(6):814-817. PubMed
  31. Kleefstra, N., Houweling, S. T., Bakker, S. J., Verhoeven, S., Gans, R. O., Meyboom-de Jong, B., and Bilo, H. J. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled tri DOI
  32. Parsons, A., Ingram, J., Inglis, J., Aveyard, P., Johnstone, E., Brown, K., Franklin, M., and Bermudez, I. A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to pr
  33. Bagdon RE and Hazen RE. Skin permeation and cutaneous hypersensitivity as a basis for making risk assessments of chromium as a soil contaminant. Environ.Health Perspect. 1991;92:111-119. PubMed
  34. Bharmal, S. V., Moyes, V., Ahmed, S., and Grossman, A. Hypoglycaemia: possible mediation by chromium salt medication. Hormones.(Athens.) 2010;9(2):181-183. PubMed
  35. Krol, E., Krejpcio, Z., Byks, H., Bogdanski, P., and Pupek-Musialik, D. Effects of chromium brewer's yeast supplementation on body mass, blood carbohydrates, and lipids and minerals in type 2 diabetic patients. Biol.Trace Elem.Res. 2011;143(2):726-737.
  36. Unisa, S., Jagannath, P., Dhir, V., Khandelwal, C., Sarangi, L., and Roy, T. K. Population-based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North India. HPB (Oxford) 2011;13(2):117-125. PubMed
  37. Noda, S., Asano, Y., and Sato, S. Lichen planus in a patient with long-term exposure to chrome. Eur.J.Dermatol. 2011;21(3):417-418. PubMed
  38. Xiang, J., Sun, Z., and Huan, J. N. Intensive chromic acid burns and acute chromium poisoning with acute renal failure. Chin Med.J.(Engl.) 7-5-2011;124(13):2071-2073.
  39. Chhabra, D., Oda, K., Jagannath, P., Utsunomiya, H., Takekoshi, S., and Nimura, Y. Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan. Asian Pac.J.Cancer Prev. 2012;13(1):187-190. PubMed
  40. Huszonek, J. Over-the-counter chromium picolinate. Am J Psychiatry 1993;150(10):1560-1561. PubMed
  41. Bunner S and McGinnis R. Chromium-induced hypoglycemia. Psychosomatics 1998;39(3):298-299. PubMed
  42. Martin, W. R. and Fuller, R. E. Suspected chromium picolinate-induced rhabdomyolysis. Pharmacotherapy 1998;18(4):860-862. DOI
  43. Proctor, D. M., Fredrick, M. M., Scott, P. K., Paustenbach, D. J., and Finley, B. L. The prevalence of chromium allergy in the United States and its implications for setting soil cleanup: a cost-effectiveness case study. Regul.Toxicol Pharmacol 1998;28(1 PubMed
  44. De Marchi S, Cecchin E, De Marchi SU. Systemic allergic dermatitis resulting from oral administration of chromium with a food supplement. Contact Dermatitis 2014;70(2):123-5. PubMed
  45. Hedberg YS, Gumulka M, Lind ML, Matura M, Lidén C. Severe occupational chromium allergy despite cement legislation. Contact Dermatitis. 2014;70(5):321-3. PubMed
  46. Thyssen JP, Jellesen MS, Møller P, Menné T, Johansen JD. Allergic chromium dermatitis from wearing 'chromium-free' footwear. Contact Dermatitis 2014;70(3):185-7. PubMed
  47. Liu Y, Cotillard A, Vatier C, et al. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial. PLoS One.
  48. Jamilian M, Asemi Z. Chromium Supplementation and the Effects on Metabolic Status in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Nutr Metab. 2015;67(1):42-8. PubMed
  49. Guimarães MM, Carvalho AC, Silva MS. Effect of chromium supplementation on the glucose homeostasis and anthropometry of type 2 diabetic patients: Double blind, randomized clinical trial: Chromium, glucose homeostasis and anthropometry. J Trace Elem Med Bi PubMed
  50. Paiva AN, Lima JG, Medeiros AC, et al. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Elem Med Biol. 2015;32:66-72. PubMed
  51. Yin RV, Phung OJ. Effect of chromium supplementation on glycated hemoglobin and fasting plasma glucose in patients with diabetes mellitus. Nutr J. 2015;14:14. PubMed
  52. Jamilian M, Zadeh Modarres S, Amiri Siavashani M, et al. The influences of chromium supplementation on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome women candidate for in vitro fertilizati
  53. Alinaghi F, Thyssen JP, Zachariae C, Johansen JD. No immediate effect of regulatory reduction of chromium in leather among adult patients with chromium allergy. Contact Dermatitis 2021;85(5):514-522. PubMed

See these in context on the Chromium monograph →

Lycopene 10 references
  1. Sharma, J. B., Kumar, A., Kumar, A., Malhotra, M., Arora, R., Prasad, S., and Batra, S. Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas. Int J Gynaecol.Obstet. 2003;81(3):257-262. PubMed
  2. Hsiao, G., Wang, Y., Tzu, N. H., Fong, T. H., Shen, M. Y., Lin, K. H., Chou, D. S., and Sheu, J. R. Inhibitory effects of lycopene on in vitro platelet activation and in vivo prevention of thrombus formation. J Lab Clin Med 2005;146(4):216-226. PubMed
  3. Clark, P. E., Hall, M. C., Borden, L. S., Jr., Miller, A. A., Hu, J. J., Lee, W. R., Stindt, D., D'Agostino, R., Jr., Lovato, J., Harmon, M., and Torti, F. M. Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse o
  4. O'Kennedy, N., Crosbie, L., Whelan, S., Luther, V., Horgan, G., Broom, J. I., Webb, D. J., and Duttaroy, A. K. Effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans. Am.J.Clin.Nutr. 2006;84(3):561-569. PubMed
  5. Jatoi, A., Burch, P., Hillman, D., Vanyo, J. M., Dakhil, S., Nikcevich, D., Rowland, K., Morton, R., Flynn, P. J., Young, C., and Tan, W. A tomato-based, lycopene-containing intervention for androgen-independent prostate cancer: results of a Phase II stu
  6. Schwenke, C., Ubrig, B., Thurmann, P., Eggersmann, C., and Roth, S. Lycopene for advanced hormone refractory prostate cancer: a prospective, open phase II pilot study. J.Urol. 2009;181(3):1098-1103. PubMed
  7. Banerjee, S., Jeyaseelan, S., and Guleria, R. Trial of lycopene to prevent pre-eclampsia in healthy primigravidas: results show some adverse effects. J.Obstet.Gynaecol.Res. 2009;35(3):477-482. PubMed
  8. Haseen, F., Cantwell, M. M., O'Sullivan, J. M., and Murray, L. J. Is there a benefit from lycopene supplementation in men with prostate cancer? A systematic review. Prostate Cancer Prostatic.Dis. 2009;12(4):325-332. PubMed
  9. Ilic, D., Forbes, K. M., and Hassed, C. Lycopene for the prevention of prostate cancer. Cochrane.Database.Syst.Rev. 2011;(11):CD008007. PubMed
  10. Sawardekar SB, Patel TC, Uchil D. Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: an in vitro study. Indian J Pharmacol 2016;48:26-31. PubMed

See these in context on the Lycopene monograph →

Copper 11 references
  1. Murry JJ, Healy MD. Drug-mineral interactions: a new responsibility for the hospital dietician. J Am Diet Assoc 1991;91:66-73.
  2. Campbell IA, Elmes PC. Ethambutol and the eye: zinc and copper (letter). Lancet 1975;2:711. DOI
  3. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  4. Kozak SF, Inderlied CB, Hsu HY, et al. The role of copper on ethambutol's antimicrobial action and implications for ethambutol-induced optic neuropathy. Diag Microbiol Infect Dis 1998;30:83-7. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  6. Cantilena LR, Klaassen CD. The effect of chelating agents on the excretion of endogenous metals. Toxicol Appl Pharmacol 1982;63:344-50.
  7. Babic Z, Tariba B, Kovacic J, Pizent A, Varnai VM, Macan J. Relevance of serum copper elevation induced by oral contraceptives: a meta-analysis. Contraception. 2013 Jun;87(6):790-800. PubMed
  8. Qui Q, Zhang F, Zhu W, Wu J, Liang M. Copper in diabetes mellitus: a meta-analysis and systematic review of plasma and serum studies. Biol Trace Elem Res 2017;177(1):53-63.
  9. Walker-Smith PK, Keith DJ, Kennedy CT, Sansom JE. Allergic contact dermatitis caused by copper. Contact Dermatitis 2016;75(3):186-7. PubMed
  10. Gallentine A. Third-degree burn on the neuropathic lower extremity in a patient with diabetes while wearing a copper-containing compression sock: a case report. Wound Manag Prev 2021;67(12):26-29. DOI
  11. Chung KJ, Chin YM, Wong MS, Sanmugam A, Singaravel S, Nah SA. Effectiveness of table salt versus copper sulphate in treating umbilical granuloma: A pilot randomized controlled trial. J Pediatr Surg 2022;57(2):261-265. PubMed

See these in context on the Copper monograph →

Manganese 21 references
  1. Hansten PD, Horn JR. Hansten and Horn's Drug Interactions Analysis and Management. Vancouver, CAN:Appl Therapeut, 1999.
  2. Barrington WW, Angle CR, Willcockson NK, et al. Autonomic function in manganese alloy workers. Environ Res 1998;78:50-8. PubMed
  3. Hauser RA, Zesiewicz TA, Martinez C, et al. Blood manganese correlates with brain magnetic resonance imaging changes in patients with liver disease. Can J Neurol Sci 1996;23:95-8. PubMed
  4. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  5. Lee JW. Manganese intoxication. Arch Neurol 2000;57:597-9.. PubMed
  6. Powers KM, Smith-Weller T, Franklin GM, et al. Parkinson's disease risks associated with dietary iron, manganese, and other nutrient intakes. Neurology 2003;60:1761-6.. PubMed
  7. McMillan, D. E. A brief history of the neurobehavioral toxicity of manganese: some unanswered questions. Neurotoxicology 1999;20(2-3):499-507.
  8. Gerber, G. B., Leonard, A., and Hantson, P. Carcinogenicity, mutagenicity and teratogenicity of manganese compounds. Crit Rev Oncol Hematol. 2002;42(1):25-34. PubMed
  9. Jiang, Y. and Zheng, W. Cardiovascular toxicities upon manganese exposure. Cardiovasc.Toxicol 2005;5(4):345-354. PubMed
  10. Mehta, R. and Reilly, J. J. Manganese levels in a jaundiced long-term total parenteral nutrition patient: potentiation of haloperidol toxicity? Case report and literature review. JPEN J Parenter.Enteral Nutr 1990;14(4):428-430. PubMed
  11. Nemery, B. Metal toxicity and the respiratory tract. Eur Respir.J 1990;3(2):202-219. DOI
  12. Vanek VW, Borum P, Buchman A, et al. A.S.P.E.N. position paper: recommendations for changes in commercially available parenteral multivitamin and multi-trace element products. Nutr Clin Pract. 2012;27:440-491.doi: 10.1177/0884533612446706 PubMed
  13. Schuh MJ. Possible Parkinson's disease induced by chronic manganese supplement ingestion. Consult Pharm. 2016;31(12):698-703. doi: 10.4140/TCP.n.2016.698. PubMed
  14. Baker B, Ali A, Isenring L. Recommendations for manganese supplementation to adult patients receiving long-term home parenteral nutrition: an analysis of the supporting evidence. Nutr Clin Pract 2016;31(2):180-5. doi: 10.1177/0884533615591600. PubMed
  15. Ho CSH, Ho RCM, Quek AML. Chronic manganese toxicity associated with voltage-gated potassium channel complex antibodies in a relapsing neuropsychiatric disorder. Int J Environ Res Public Health 2018;15(4). pii: E783. doi: 10.3390/ijerph15040783. PubMed
  16. Yamamoto M, Sakurai K, Eguchi A, et al.; Japan Environment and Children's Study Group: Association between blood manganese level during pregnancy and birth size: the Japan environment and children's study (JECS). Environ Res 2019;172:117-26. PubMed
  17. Li D, Ge X, Liu Z, et al. Association between long-term occupational manganese exposure and bone quality among retired workers. Environ Sci Pollut Res Int 2020;27(1):482-9. PubMed
  18. Martin KV, Sucharew H, Dietrich KN, et al. Co-exposure to manganese and lead and pediatric neurocognition in East Liverpool, Ohio. Environ Res 2021;202:111644. PubMed
  19. Racette BA, Nelson G, Dlamini WW, et al. Depression and anxiety in a manganese-exposed community. Neurotoxicology 2021;85:222-33. PubMed
  20. Ruiz-Azcona L, Fernández-Olmo I, Expósito A, et al. Impact of environmental airborne manganese exposure on cognitive and motor functions in adults: a systematic review and meta-analysis. Int J Environ Res Public Health 2021;18(8):4075. PubMed
  21. Uyar E, Gurkas E, Aksu AU, et al. Can therapeutic plasma exchange be life-saving in life-threatening manganese intoxication?. Transfus Apher Sci 2022;61(4):103417. PubMed

See these in context on the Manganese monograph →

Same 31 references
  1. Perna AF, Castaldo P, Ingrosso D, et al. Homocysteine, a new cardiovascular risk factor, is also a powerful uremic toxin. J Nephrol 1999;12:230-40.
  2. Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999;30:1081-9. PubMed
  3. Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522. PubMed
  4. Bradley JD, Flusser D, Katz BP, et al. A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis. J Rheumatol 1994;21:905-11.
  5. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Psychiatry Res 1992;44:257-62. PubMed
  6. Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147:591-5. PubMed
  7. Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432-6. PubMed
  8. Domljan Z, Vrhovac B, Durrigl T, Pucar I. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 1989;27:329-33.
  9. Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 1987;83:89-94. PubMed
  10. Lipinski JF, Cohen BM, Frankenburg F, et al. Open trial of S-adenosylmethionine for treatment of depression. Am J Psychiatry 1984;141:448-50.
  11. Almasio P, Bortolini M, Pagliaro L, Coltorti M. Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis. Drugs 1990;40:111-23. PubMed
  12. Friedel HA, Goa KL, Benfield P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 1989;38:389-416. PubMed
  13. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52. PubMed
  14. Frezza M, Centini G, Cammareri G, et al. S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepatogastroenterology 1990;37:122-5.
  15. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  16. Charlton CG, Crowell B Jr. Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav 1992;43:423-31..
  17. Goren JL, Stoll AL, Damico KE, et al. Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans. Pharmacotherapy 2004;24:1501-7. PubMed
  18. Arnold O, Saletu B, Anderer P, et al. Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry. Eur Neuropsychopharmacol 2005; PubMed
  19. Nelson JC. S-adenosyl methionine (SAMe) augmentation in major depressive disorder. (Editorial). Am J Psychiatry 2010;167:889-91.
  20. Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther 2009; PubMed
  21. Manzillo G, Piccinino F, Surrenti C, et al. Multicentre double-blind placebo-controlled study of intravenous and oral S-adenosyl-L-methionine (SAMe) in cholestatic patients with liver disease. Drug Invest 1992;4 (Suppl 4):90-100. DOI
  22. Carrieri PB, Indaco A, Gentile S, et al. S-adenosylmethionine treatment of depressioin in patients with Parkinson's disease: a double-blind, crossover study versus placebo. Curr Ther Res 1990;48(1):154-60.
  23. Pancheri P, Scapicchio P, Delle Chiaie R. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuro PubMed
  24. Medici V., Virata M. C., Peerson J. M., Stabler S. P., French S. W., Gregory J. F. III, Albanese A., Bowlus C. L., Devaraj S., Panacek E. A., Richards J. R., Halsted C. H. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, ra
  25. Chitiva, H., Audivert, F., and Alvarez, C. Suicide attempt by self-burning associated with ingestion of S-adenosylmethionine: a review of the literature and case report. J.Nerv.Ment.Dis. 2012;200(1):99-101. PubMed
  26. Carney, M. W., Edeh, J., Bottiglieri, T., Reynolds, E. M., and Toone, B. K. Affective illness and S-adenosyl methionine: a preliminary report. Clin Neuropharmacol. 1986;9(4):379-385. PubMed
  27. Miccoli, L., Porro, V., and Bertolino, A. Comparison between the antidepressant activity and of S- adenosylmethionine (SAMe) and that of some tricyclic drugs. Acta Neurol (Napoli) 1978;33 (3):243-255.
  28. Bacci, Ballerini F., Lopez, Anguera A., Alcaraz, P., and Hernandez, Reyes N. [SAMe in the management of postconcussional syndrome]. Medicina Clinica (Barc.) 1983;80(4):161-164.
  29. Muscettola G, Galzenati M, Balbi A. SAMe versus placebo: a double blind comparison in major depressive disorders. Advances in Biochemical Psychopharmacology 1982;32:151-6.
  30. Capretto C, Cremona C, and Canaparo L. A double-blind controlled study of S-adenosylmethionine (SAMe) v. ibuprofen in gonarthrosis, coxarthrosis and spondylarthrosis. Clin Trials J 1985;22(1):15-24.
  31. Ancarani E, Biondi B, Bolletta A, et al. Major depression complicating hemodialysis in patients with chronic renal failure: a multicenter, double-blind, controlled clinical trial of S-adenosyl-L-methionine versus placebo. Curr Ther Res 1993;54(6):680-6. DOI

See these in context on the Same monograph →

Black Pepper 29 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  3. Bano G, Amla V, Raina RK, et al. The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 1987;53:568-9. PubMed
  4. Bano G, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991;41;615-7. PubMed
  5. Cohle SD, Trestrail JD III, Graham MA, et al. Fatal pepper aspiration. Am J Dis Child 1988;142:633-6. PubMed
  6. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  7. Velpandian T, Jasuja R, Bhardwaj RK, et al. Piperine in food: interference in the pharmacokinetics of phenytoin. Eur J Drug Metab Pharmacokinet 2001;26:241-7. PubMed
  8. Pattanaik S, Hota D, Prabhakar S, et al. Pharmacokinetic interaction of a single dose of piperine with steady-state carbamazepine in epilepsy patients. Phytother Res 2009;23:1281-6.
  9. Munakata, M., Kobayashi, K., Niisato-Nezu, J., Tanaka, S., Kakisaka, Y., Ebihara, T., Ebihara, S., Haginoya, K., Tsuchiya, S., and Onuma, A. Olfactory stimulation using black pepper oil facilitates oral feeding in pediatric patients receiving long-term en
  10. Myers, B. M., Smith, J. L., and Graham, D. Y. Effect of red pepper and black pepper on the stomach. Am J Gastroenterol 1987;82(3):211-214.
  11. Raghavendra, R. H. and Naidu, K. A. Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis. Prostaglandins Leukot.Essent.Fatty Acids 2009;81(1):73-78. PubMed
  12. Subehan, Usia, T., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum. Planta Med 2006;72(6):527-532.
  13. Kasibhatta, R. and Naidu, M. U. Influence of piperine on the pharmacokinetics of nevirapine under fasting conditions: a randomised, crossover, placebo-controlled study. Drugs R.D. 2007;8(6):383-391. PubMed
  14. Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., and Tezuka, Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73. PubMed
  15. Mujumdar, A. M., Dhuley, J. N., Deshmukh, V. K., Raman, P. H., Thorat, S. L., and Naik, S. R. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp.Biol. 1990;28(5):486-487.
  16. Panda, S. and Kar, A. Piperine lowers the serum concentrations of thyroid hormones, glucose and hepatic 5'D activity in adult male mice. Horm.Metab Res. 2003;35(9):523-526. PubMed
  17. Lawless, H. and Stevens, D. A. Effects of oral chemical irritation on taste. Physiol Behav. 1984;32(6):995-998. PubMed
  18. Hiwale, A. R., Dhuley, J. N., and Naik, S. R. Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats. Indian J Exp.Biol. 2002;40(3):277-281.
  19. Han, Y., Chin Tan, T. M., and Lim, L. Y. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol.Appl.Pharmacol. 8-1-2008;230(3):283-289. PubMed
  20. Sharma, P., Varma, M. V., Chawla, H. P., and Panchagnula, R. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Farmaco 2005;60(11-12):874-883. PubMed
  21. Aher, S., Biradar, S., Gopu, C. L., and Paradkar, A. Novel pepper extract for enhanced P-glycoprotein inhibition. J Pharm.Pharmacol. 2009;61(9):1179-1186. PubMed
  22. Zutshi, R. K., Singh, R., Zutshi, U., Johri, R. K., and Atal, C. K. Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis. J Assoc.Physicians India 1985;33(3):223-224.
  23. Marotta, R. B. and Floch, M. H. Diet and nutrition in ulcer disease. Med Clin North Am 1991;75(4):967-979. PubMed
  24. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
  25. Gimenez L, Zacharisen M. Severe pepper allergy in a young child. WMJ. 2011 Jun;110(3):138-9.
  26. Ren T, Yang M, Xiao M, Zhu J, Xie W, Zuo Z. Time-dependent inhibition of carbamazepine metabolism by piperine in anti-epileptic treatment. Life Sci. 2019;218:314-323. PubMed
  27. Thomas AB, Choudhary DC, Raje A, Nagrik SS. Pharmacokinetics and pharmacodynamic herb-drug interaction of piperine with atorvastatin in rats. J Chromatogr Sci 2021;59(4):371-80. PubMed
  28. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  29. Lin F, Hu Y, Zhang Y, Zhao L, Zhong D, Liu J. Predicting Food-Drug Interactions between Piperine and CYP3A4 Substrate Drugs Using PBPK Modeling. Int J Mol Sci 2024;25(20):10955. PubMed

See these in context on the Black Pepper monograph →

Bilberry 14 references
  1. Cignarella A, Nastasi M, Cavalli E, Puglisi L. Novel lipid-lowering properties of Vaccinium myrtillus L. leaves, a traditional antidiabetic treatment, in several models of rat dyslipidaemia: a comparison with ciprofibrate. Thromb Res 1996;84:311-22. PubMed
  2. Morazzoni P, Magistretti MJ. Activity of Myrtocyan, an anthosyanoside complex from Vaccinium myrtillus (VMA), on platelet aggregation and adhesiveness. Fitoterapia 1990;61:13-21.
  3. Erlund, I., Koli, R., Alfthan, G., Marniemi, J., Puukka, P., Mustonen, P., Mattila, P., and Jula, A. Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 2008;87(2):323-331. PubMed
  4. Hawrelak, J. A. and Myers, S. P. Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study. J Altern Complement Med 2010;16(10):1065-1071. PubMed
  5. Morazzoni P and Magistretti MJ. Effects of Vaccinium myrtillus anthocyanosides on prostacyclin-like activity in rat arterial issue. Fitoterapia 1986;57:11-14.
  6. Pulliero G, Montin S, Bettini V, and et al. Ex vivo study of the inhibitory effects of Vaccinium myrtillus anthocyanosides on human platelet aggregation. Fitoterapia 1989;60:69-75.
  7. Bottecchia D. Preliminary report on the inhibitory effect of vaccinium myrtillus anthocyanosides on platelet aggregation and clot retraction. Fitoterapia 1987;48:3-8.
  8. Fdez, M., Zaragoza, F., and Alvarez, P. In vitro platelet aggregation effects of anthocyanosides of vaccinium myrtilus L. Anales de la Real Academia de Farmacia 1983;49:79-90.
  9. Biedermann L, Mwinyi J, Scharl M, Frei P, Zeitz J, Kullak-Ublick GA, et al. Bilberry ingestion improves disease activity in mild to moderate ulcerative colitis-an open pilot study. 2013 May;7(4):271-9. PubMed
  10. Hoggard N, Cruickshank M, Moar KM, Bestwick C, Holst J, Russell W, et al. A single supplement of a standardized bilberry (Vaccinium myrtillus L.) extract (36% wet weight anthocyanins) modifies glycaemic response in individuals with type 2 diabetes control
  11. Aichinger G, Pahlke G, Nagel LJ, Berger W, Marko D. Bilberry extract, its major phenolic compounds, and soy isoflavone genistein antagonize the cytostatic drug erlotinib in human epithelial cells. Food Funct 2016;7(8):3628-36.
  12. Prokop J, Ln&ecaron;ni&ccaron;kov&aacute; K, Cibicek N, et al. Effect of bilberry extract (Vaccinium myrtillus L.) on drug-metabolizing enzymes in rats. Food Chem Toxicol 2019;129:382-90. PubMed
  13. Chan SW, Chu TTW, Choi SW, Benzie IFF, Tomlinson B. Impact of short-term bilberry supplementation on glycemic control, cardiovascular disease risk factors, and antioxidant status in Chinese patients with type 2 diabetes. Phytother Res 2021. Online ahead o PubMed
  14. Bøhn SK, Myhrstad MCW, Thoresen M, et al. Bilberry/red grape juice decreases plasma biomarkers of inflammation and tissue damage in aged men with subjective memory impairment -a randomized clinical trial. BMC Nutr 2021;7(1):75. PubMed

See these in context on the Bilberry monograph →

Lecithin 9 references
  1. Buchman AL, Dubin M, Jenden D, et al. Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology 1992;102:1363-70.
  2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  3. Chatellier G, Lacomblez L. Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. Groupe Francais d'Etude de la Tetrahydroaminoacridine. BMJ 1990;300:495-9.
  4. Gelenberg AJ, Dorer DJ, Wojcik JD, et al. A crossover study of lecithin treatment of tardive dyskinesia. J Clin Psychiatry 1990;51:149-53.
  5. Little A, Levy R, Chuaqui-Kidd P, Hand D. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease. J Neurol Neurosurg Psychiatry 1985;48:736-42. PubMed
  6. Palm M, Moneret-Vautrin DA, Kanny G, et al. Food allergy to egg and soy lecithins. Allergy 1999;54:1116-7. PubMed
  7. Drachman DA, Glosser G, Fleming P, et al. Memory decline in the aged: treatment with lecithin and physostigmine. Neurology 1982;32:944-50. PubMed
  8. Gelenberg, A. J., Doller-Wojcik, J. C., and Growdon, J. H. Choline and lecithin in the treatment of tardive dyskinesia: preliminary results from a pilot study. Am J Psychiatry 1979;136(6):772-776. PubMed
  9. Electronic Code of Federal Regulations. Title 21, Chapter 1, Subchapter B, Part 184: Direct food substances affirmed as Generally Recognized as Safe. Subpart B - listing of specific substances affirmed as GRAS. Sec. 184.1400 Lecithin. Available at: https:

See these in context on the Lecithin monograph →

Betaine Hydrochloride 2 references
  1. Yago MR, Frymoyer A, Benet LZ, Smelick GS, Frassetto LA, Ding X, Dean B, Salphati L, Budha N, Jin JY, Dresser MJ, Ware JA. The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria. AAPS J. 2014 PubMed
  2. Yago MR, Frymoyer AR, Smelick GS, Frassetto LA, Budha NR, Dresser MJ, Ware JA, Benet LZ. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria. Mol Pharm. 2013 Nov 4;10(11):4032-7. PubMed

See these in context on the Betaine Hydrochloride monograph →

Milk Thistle 69 references
  1. Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;9:105-13. PubMed
  2. Anon. Milk thistle: Effects on liver disease and cirrhosis and clinical adverse effects. Summary, Evidence Report/Technology Assessment: Number 21, September 2000. Agency for Healthcare Research and Quality, Rockville, MD. Available at: http://www.ahrq.g
  3. Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, et al. Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 2000;86:250-6. PubMed
  4. Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3. DOI
  5. Kim DH, Jin YH, Park JB, Kobashi K. Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull 1994;17:443-5. PubMed
  6. Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998;28:615-21. PubMed
  7. Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002;22:551-6. PubMed
  8. Boerth J, Strong KM. The clinical utility of milk thistle (Silybum marianum) in cirrhosis of the liver. J Herb Pharmacother 2002;2:11-7.
  9. Tanamly MD, Tadros F, Labeeb S, et al. Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis 2004;36:752-9. PubMed
  10. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004;76:428-40. .
  11. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006;20;1036-9.
  12. Deng JW, Shon JH, Shin HJ, et al. Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharm Res 2008;25:1807-14. PubMed
  13. Kim CS, Choi SJ, Park CY, et al. Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats. Anticancer Res 2010;30:79-85.
  14. Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94. PubMed
  15. van Erp NP, Baker SD, Zhao M, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 2005;11:7800-6.
  16. Budzinski JW, Trudeau VL, Drouin CE, et al. Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol 2007;85:966-78.
  17. Doehmer J, Weiss G, McGregor GP, Appel K. Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro 2011;25:21-7. PubMed
  18. Jiao Z, Shi XJ, Li ZD, et al. Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients. Br.J.Clin.Pharmacol. 2009;68(1):47-60.
  19. Gurley, B. J., Barone, G. W., Williams, D. K., Carrier, J., Breen, P., Yates, C. R., Song, P. F., Hubbard, M. A., Tong, Y., and Cheboyina, S. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin phar
  20. Allain, H., Schuck, S., Lebreton, S., Strenge-Hesse, A., Braun, W., Gandon, J. M., and Brissot, P. Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease. Dement.Geriatr.Cogn Disord. 1999;10(3):181-185. PubMed
  21. Angulo, P., Patel, T., Jorgensen, R. A., Therneau, T. M., and Lindor, K. D. Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 2000;32(5):897-900. PubMed
  22. Bean, P. The use of alternative medicine in the treatment of hepatitis C. Am.Clin.Lab 2002;21(4):19-21.
  23. Hussain, S. A. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J.Med.Food 2007;10(3):543-547. PubMed
  24. El-Kamary, S. S., Shardell, M. D., Abdel-Hamid, M., Ismail, S., El-Ateek, M., Metwally, M., Mikhail, N., Hashem, M., Mousa, A., Aboul-Fotouh, A., El-Kassas, M., Esmat, G., and Strickland, G. T. A randomized controlled trial to assess the safety and effic
  25. Gharagozloo, M., Moayedi, B., Zakerinia, M., Hamidi, M., Karimi, M., Maracy, M., and Amirghofran, Z. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. Fundam.Clin.Pharmaco
  26. Ladas, E. J., Kroll, D. J., Oberlies, N. H., Cheng, B., Ndao, D. H., Rheingold, S. R., and Kelly, K. M. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL PubMed
  27. Sayyah, M., Boostani, H., Pakseresht, S., and Malayeri, A. Comparison of Silybum marianum (L.) Gaertn. with fluoxetine in the treatment of Obsessive-Compulsive Disorder. Prog.Neuropsychopharmacol.Biol.Psychiatry 3-17-2010;34(2):362-365. PubMed
  28. Flaig, T. W., Glode, M., Gustafson, D., van, Bokhoven A., Tao, Y., Wilson, S., Su, L. J., Li, Y., Harrison, G., Agarwal, R., Crawford, E. D., Lucia, M. S., and Pollak, M. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients w
  29. Ramirez-Santos, A., Perez-Bustillo, A., Gonzalez-Sixto, B., Suarez-Amor, O., and Rodriguez-Prieto, M. A. [Acute generalized exanthematous pustulosis due to milk thistle (Silybum marianum) tea]. Actas Dermosifiliogr. 2011;102(9):744-745. DOI
  30. Loguercio C, Andreone P, Brisc C, et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic Biol Med 2012;52(9):1658-65. PubMed
  31. Yakoot, M. and Salem, A. Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial. BMC.Gastroenterol. 2012;12:32. PubMed
  32. Fallahzadeh, M. K., Dormanesh, B., Sagheb, M. M., Roozbeh, J., Vessal, G., Pakfetrat, M., Daneshbod, Y., Kamali-Sarvestani, E., and Lankarani, K. B. Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic
  33. Fried, M. W., Navarro, V. J., Afdhal, N., Belle, S. H., Wahed, A. S., Hawke, R. L., Doo, E., Meyers, C. M., and Reddy, K. R. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon t
  34. Fallah Huseini, H., Larijani, B., Fakhrzadeh, H., Rajabi Pour, B., Akhondzadeh, S., Toliat, T., and Heshmat, R. The clinical trial of Silybum Marianum seed extract (Silymarin) on type II diabetic patients with hyperlipidemia. Iran J.Diabetes Lipid Disord
  35. Mironets VI, Krasovskaia EA, and Polishchuk II. [A case of urticaria during Carsil treatment]. Vrach Delo 1990;7:86-87.
  36. Velussi M, Cernigoi AM, Viezzoli L, and et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Curr Ther Res 1993;53(5):533-545. DOI
  37. Marcelli R, Bizzoni P, Conte D, and et al. Randomized controlled study of the efficacy and tolerability of a short course of IdB 1016 in the treatment of chronic persistent hepatitis. Eur Bull Drug Res 1992;1(3):131-135.
  38. Vailati A, Aristia L, Sozze E, and et al. Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 1993;64(3):219-228.
  39. Marena C and Lampertico M. Preliminary clinical development of silipide: a new complex of silybin in toxic liver disorders. Planta Med 1991;57(2):A124-A125. DOI
  40. Grungreiff K, Albrecht M, and Strenge-Hesse A. Benefit of medicinal liver therapy in general practice. Med Welt 1995;46:222-227.
  41. Frerick F, Kuhn U, and Strenge-Hesse A. Silymarin--ein Phytopharmakon zur Behandlung toxischen Leberschaden: Anwendungsbeobachtung bei 2169 Patienten. Kassenarzt 1990;33:36-41.
  42. Schuppan D, Strosser W, Burkard G, and et al. Influence of Legalon(TM) 140 on the metabolism of collagen in patients with chronic liver disease--Review by measurement of PIIINP-values. Zeitschrift fur Allgemeinmedizin 1998;74:577-584.
  43. Studlar M. Die Behandlung chronischer Leberkrankungen mit Silymarin und B-Vitaminen. Therapiewoche 1985;35:3375-3378.
  44. Anon. Adverse reaction: milk thistle-associated toxicity. Nurse Drug Alert 1999;23(7):51.
  45. Gufford BT, Chen G, Vergara AG, et al. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction. Drug Metab Dispos. 2015;43(9):1353-9. PubMed
  46. El-Shitany NA, Hegazy S, El-Desoky K. Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine. 2010;17(2):116-25. PubMed
  47. Seidlová-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W. Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx
  48. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  49. Derosa G, Romano D, D'Angelo A, Maffioli P. Berberis aristata/Silybum marianum fixed combination (Berberol(®)) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial. Phyto PubMed
  50. Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015;15:334. PubMed
  51. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-6. PubMed
  52. Rastegarpanah M, Malekzadeh R, Vahedi H, et al. A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis. Chin J Integr Med. 2015;21(12):902-6. PubMed
  53. Di Pierro F, Bellone I, Rapacioli G, Putignano P. Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins. Diabetes Metab Syndr Obes. 2015;8:8 PubMed
  54. Di Pierro F, Villanova N, Agostini F, Marzocchi R, Soverini V, Marchesini G. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control. Diabetes Metab Syndr Obes. 2012;5:213-7. PubMed
  55. Guarino G, Strollo F, Carbone L, et al. Bioimpedance analysis, metabolic effects and safety of the association Berberis aristata/Bilybum marianum: a 52-week double-blind, placebo-controlled study in obese patients with type 2 diabetes. J Biol Regul Homeos
  56. Ebrahimpour-Koujan S, Gargari BP, Mobasseri M, Valizadeh H, Asghari-Jafarabadi M. Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A T
  57. Lash DB, Ward S. CYP2C9-mediated warfarin and milk thistle interaction. J Clin Pharm Ther. 2019. PubMed
  58. Malekshah RE, Khaleghian A. Influence of Silybum marianum on morphine addicted rats, biochemical parameters and molecular simulation studies on µ-opioid receptor. Drug Res (Stuttg). 2019;69(11):630-638. PubMed
  59. Soleymani S, Ayati MH, Mansourzadeh MJ, Namazi N, Zargaran A. The effects of Silymarin on the features of cardiometabolic syndrome in adults: A systematic review and meta-analysis. Phytother Res. 2022 Jan 11. doi: 10.1002/ptr.7364. PubMed
  60. Gamissans M, Expósito-Serrano V, López-Llunell C, Valdivieso L, Garbayo-Salmons P. Bullous pemphigoid triggered by Silybum marianum: an unexpected side effect of an herbal remedy. Int J Dermatol. 2021 Aug 7. doi: 10.1111/ijd.15822. PubMed
  61. Aboras SI, Korany MA, El-Yazbi AF, Ragab MAA, Abdine HH. In-depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 and ledipasvir in rat plasma using LC-MS. Biomed Chromatogr 2022;36(9):e5427. PubMed
  62. Wattanakrai P, Nimmannitya K. A Randomized, Double-Blind, Split-Face Study of Topical Silymarin vs 2% Hydroquinone Cream in Melasmas. J Drugs Dermatol 2022;21(12):1304-1310. PubMed
  63. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
  64. Zhang W, Zhang Y, Wen C, Jiang X, Wang L. In vitro Assessment of the Effects of Silybin on CYP2B6-mediated Metabolism. Planta Med 2023. PubMed
  65. Bechtold BJ, Lynch KD, Oyanna VO, et al. Rifampin- and Silymarin-Mediated Pharmacokinetic Interactions of Exogenous and Endogenous Substrates in a Transgenic OATP1B Mouse Model. Mol Pharm 2024;21(5):2284-2297. PubMed
  66. Mohammadi S, Asbaghi O, Afrisham R, et al. Impacts of Supplementation with Silymarin on Cardiovascular Risk Factors: A Systematic Review and Dose-Response Meta-Analysis. Antioxidants (Basel) 2024;13(4):390. PubMed
  67. Rustamzadeh A, Sadigh N, Vahabi Z, et al. Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer's patients: A double-blind placebo-controlled randomized clinical trial. IBRO Neurosci Rep 2024;17:108-121. PubMed
  68. Fatemi Shandiz A, Karimi G, Dayyani M, Hosseini S, Elyasi S. Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer. J Oncol Pharm Pract 2024. PubMed
  69. Duan X, Bai W, Hu J, et al. Inhibitory effect of flavonoids on multidrug and toxin extrusion protein 1 function: Implications for food/herb-drug interaction and drug-induced kidney injury. J Appl Toxicol 2024;44(9):1388-1402. PubMed

See these in context on the Milk Thistle monograph →

Hawthorn 25 references
  1. Tauchert M. Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J 2002;143:910-5. PubMed
  2. Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med 2003;114:665-74.. PubMed
  3. Chang Q, Zuo Z, Harrison F, Chow MS. Hawthorn. J Clin Pharmacol 2002;42:605-12.
  4. Holubarsch CJ, Colucci WS, Meinertz T, et al. The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: the SPICE trial. Eur J Heart Fail 2008;10:1255-63. PubMed
  5. Pittler MH, Guo R, and Ernst E. Hawthorn extract for treating chronic heart failure. Cochrane.Database.Syst Rev 2008:CD005312. PubMed
  6. Zick SM, Vautaw BM, Gillespie B, Aaronson KD. Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) trial. Eur J Heart Fail. 2009;11:990-99. PubMed
  7. Werner NS, Duschek S, and Schandry R. D-camphor-crataegus berry extract combination increases blood pressure and cognitive functioning in the elderly - a randomized, placebo controlled double blind study. Phytomedicine. 2009;16:1077-82. PubMed
  8. Dalli E, Colomer E, Tormos MC, et al. Crataegus laevigata decreases neutrophil elastase and has hypolipidemic effect: a randomized, double-blind, placebo-controlled trial. Phytomedicine. 6-15-2011;18:769-75. PubMed
  9. Maek-a-nantawat W, Phonrat B, Dhitavat J, et al. Safety and efficacy of CKBM-A01, a Chinese herbal medicine, among asymptomatic HIV patients. Southeast Asian J Trop.Med Public Health 2009;40:494-501.
  10. Asher GN, Viera AJ, Weaver MA, et al. Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial. BMC.Complement Altern.Med 2012;12:26. PubMed
  11. Walker AF, Marakis G, Simpson E, et al. Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial. Br J Gen.Pract 2006;56:437-43.
  12. Daniele C, Mazzanti G, Pittler MH, et al. Adverse-event profile of Crataegus spp.: a systematic review. Drug Saf 2006;29:523-35. PubMed
  13. Tankanow R, Tamer HR, Streetman DS, et al. Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). J.Clin.Pharmacol. 2003;43:637-42. DOI
  14. Tauchert, M., Gildor, A., and Lipinski, J. [High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure]. Herz 1999;24(6):465-474.
  15. Horoz, M., Gok, E., Genctoy, G., Ozcan, T., Olmaz, R., Akca, M., Kiykim, A., and Gurses, I. Crataegus orientalis associated multiorgan hypersensitivity reaction and acute renal failure. Intern.Med 2008;47(23):2039-2042. PubMed
  16. Dalli, E., Valles, J., Cosin-Sales, J., Santos, M. T., Moscardo, A., Milara, J., and Sotillo, J. F. Effects of hawthorn (Crataegus laevigata) on platelet aggregation in healthy volunteers. Thromb.Res 2011;128(4):398-400. PubMed
  17. Rogov VD. [Toxiderma due to the fruits of the hawthorn]. Vestn Dermatol Venerol 1984;7(7):46-47.
  18. Loew D, Albrecht M, and Podzuweit H. Efficacy and tolerability of a Hawthorn preparation in patients with heart failure Stage I and II according to NYHA - a surveillance study. Phytomedicine 1996;3(Suppl 1):92.
  19. Rababa'h AM, Altarabsheh SE, Haddad O, Deo SV, Obeidat Y, Al-Azzam S. Hawthorn Herb Increases the Risk of Bleeding after Cardiac Surgery: An Evidence-Based Approach. Heart Surg Forum 2016;19(4):E175-9. PubMed
  20. Shatoor AS, Soliman H, Al-Hashem F, Gamal BE, Othman A, El-Menshaw N. Effect of hawthorn (Crataegus aronia syn. Azarolus (L)) on platelet function in albino wistar rats. Thromb Res 2012;130(1):75-80. PubMed
  21. Vibes J, Lasserre B, Gleye J, Declume C. Inhibition of thromboxane A2 biosynthesis in vitro by the main components of Crataegus oxyacantha (hawthorn) flower heads. Prostaglandins Leukot Essent Fatty Acids 1994;50(4):173-5. PubMed
  22. Rogers KL, Grice ID, Griffiths LR. Inhibition of platelet aggregation and 5-HT release by extracts of Australian plants used traditionally as headache treatments. Eur J Pharm Sci 2000;9(4):355-63. PubMed
  23. Zhou CC, Huang XX, Gao PY, et al. Two new compounds from Crataegus pinnatifida and their antithrombotic activities. J Asian Nat Prod Res 2014;16(2):169-74.
  24. Palmer KG, Lebin JA, Cronin MT, Mazor SS, Burns RA. Crataegus mexicana (Tejocote) Exposure Associated with Cardiotoxicity and a Falsely Elevated Digoxin Level. J Med Toxicol. 2019;15(4):295-298. PubMed
  25. Espinosa J, Bassett R, Lucerna A, Finn D. Hawthorne root (Crataegus mexicana) toxicity. Am J Emerg Med. 2024;78:242.e5-242.e6. PubMed

See these in context on the Hawthorn monograph →

Quercetin 26 references
  1. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category III chronic prostatitis: A preliminary prospective, double-blind, placebo-controlled trial. Urol 1999;54:960-3. PubMed
  2. Starvic B. Quercetin in our diet: from potent mutagen to probable anticarcinogen. Clin Biochem 1994;27:245-8. PubMed
  3. Ferry DR, Smith A, Malkhandi J, et al. Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 1996;2:659-67..
  4. Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John's wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther 2000;294:88-95. DOI
  5. Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007;137:2405-11.
  6. Kim KA, Park PW, Kim HK, et al. Effect of quercetin on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in healthy subjects. J Clin Pharmacol 2005;45:941-6. PubMed
  7. DiCenzo R, Frerichs V, Larppanichpoonphol P, et al. Effect of quercetin on the plasma and intracellular concentrations of saquinavir in healthy adults. Pharmacotherapy 2006;26:1255-61. PubMed
  8. Choi JS, Choi BC, Choi KE. Effect of quercetin on the pharmacokinetics of oral cyclosporine. Am J Health Syst Pharm 2004;61:2406-9. PubMed
  9. Choi JS, Jo BW, Kim YC. Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin. Eur J Pharm Biopharm 2004;57:313-8. PubMed
  10. Vaclavikova R, Horsky S, Simek P, Gut I. Paclitaxel metabolism in rat and human liver microsomes is inhibited by phenolic antioxidants. Naunyn Schmiedebergs Arch Pharmacol 2003;368:200-9. PubMed
  11. Di Bari L, Ripoli S, Pradhan S, Salvadori P. Interactions between quercetin and warfarin for albumin binding: A new eye on food/drug interference. Chirality 2010;22:593-6. PubMed
  12. Lamson, D. W. and Brignall, M. S. Antioxidants and cancer, part 3: quercetin. Altern.Med.Rev. 2000;5(3):196-208.
  13. Duan KM, Wang SY, Ouyang W, Mao YM, Yang LJ. Effect of quercetin on CYP3A activity in Chinese healthy participants. J Clin Pharmacol 2012;52(6):940-6. PubMed
  14. Wang SY, Duan KM, Li Y, et al. Effect of quercetin on P-glycoprotein transport ability in Chinese healthy subjects. Eur J Clin Nutr 2013;67(4):390-4. PubMed
  15. Nguyen MA, Staubach P, Wolffram S, Langguth P. Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans - Implications for the evaluation of transporter-mediated flavonoid-drug interactions. Eur J Pha PubMed
  16. Wu LX, Guo CX, Chen WQ, et al. Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: an in vitro and in vivo assessment. Br J Clin Pharmacol 2012;73(5):750-7.
  17. Ahrens MJ, Thompson DL. Effect of emulin on blood glucose in type 2 diabetics. J Med Food. 2013;16(3):211-5. PubMed
  18. Larson A, Witman MA, Guo Y, et al. Acute, quercetin-induced reductions in blood pressure in hypertensive individuals are not secondary to lower plasma angiotensin-converting enzyme activity or endothelin-1: nitric oxide. Nutr Res. 2012;32(8):557-64. PubMed
  19. Bedada SK, Neerati P. Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers. Phytother Res. 2018 Feb;32(2):305-311. doi: 10.1002/ptr.5978. PubMed
  20. Zhao Q, Wei J, Zhang H. Effects of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. Xenobiotica 2019;49(5):563-8. PubMed
  21. Bhutani P, Rajanna PK, Paul AT. Impact of quercetin on pharmacokinetics of quetiapine: insights from in-vivo studies in wistar rats. Xenobiotica. 2020:1-7.
  22. Li C, Wang X, Bi Y, et al. Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy. Toxicol Sci. 2020;175(2):279-291. PubMed
  23. Ni Y, Duan Z, Zhou D, et al. Identification of Structural Features for the Inhibition of OAT3-Mediated Uptake of Enalaprilat by Selected Drugs and Flavonoids. Front Pharmacol. 2020;11:802. PubMed
  24. Song YK, Yoon JH, Woo JK, et al. Quercetin is a flavonoid breast cancer resistance protein inhibitor with an impact on the oral pharmacokinetics of sulfasalazine in rats. Pharmaceutics 2020;12(5):397. PubMed
  25. Ahmad E, Jahangir M, Ismail MA, et al. Influence of quercetin pretreatment on pharmacokinetics of warfarin in rats. Curr Drug Saf 2022. PubMed
  26. Nambiar A, Kellogg D 3rd, Justice J, et al. Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability. EBioMedicine 20 PubMed

See these in context on the Quercetin monograph →

Vitamin B6 32 references
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
  4. South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  6. Baxter P, Aicardi J. Neonatal seizures after pyridoxine use. Lancet 1999;354:2082-3. PubMed
  7. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
  8. Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
  9. Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
  10. Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
  11. Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
  12. Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
  13. Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
  14. Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
  15. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
  16. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  17. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  18. Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
  19. Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
  20. de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
  21. Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
  22. Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
  23. Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
  24. Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
  25. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  26. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  27. Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
  28. Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
  29. Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
  30. Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
  31. Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
  32. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed

See these in context on the Vitamin B6 monograph →

Bacopa 12 references
  1. Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology 2001;156:481-4..
  2. Yadav SK, Jain AK, Tripathi SN, Gupta JP. Irritable bowel syndrome: therapeutic evaluation of indigenous drugs. Indian J Med Res 1989;90:496-503..
  3. Morgan A, Stevens J. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med 2010;16:753-9.
  4. Kar, A., Panda, S., and Bharti, S. Relative efficacy of three medicinal plant extracts in the alteration of thyroid hormone concentrations in male mice. J Ethnopharmacol. 2002;81(2):281-285. PubMed
  5. Mukherjee, G. D. and Dey, C. D. Clinical trial on Brahmi. I. J.Exp.Med.Sci. 1966;10(1):5-11.
  6. Kar A, Pandit S, Mukherjee K, Bahadur S, Mukherjee PK. Safety assessment of selected medicinal food plants used in Ayurveda through CYP450 enzyme inhibition study. J Sci Food Agric 2017;97(1):333-40. doi: 10.1002/jsfa.7739. PubMed
  7. Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, et al. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol 2014;151(1):528-35. PubMed
  8. Ramasamy S, Kiew LV, Chung LY. Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents. Molecules 2014;19(2):2588-601. PubMed
  9. Prabhakar S, Vishnu VY, Modi M, et al. Efficacy of Bacopa monnieri (Brahmi) and donepezil in Alzheimer's disease and mild cognitive impairment: a randomized double-blind parallel phase 2b study. Ann Indian Acad Neurol 2020;23(6):767-73. PubMed
  10. Acquarulo B, Tandon P, Macica CM. Suspected cholinergic toxicity due to cevimeline hydrochloride and Bacopa monnieri interaction: a case report. J Med Case Rep 2022;16(1):253. PubMed
  11. Keegan AP, Stough C, Paris D, et al. Bacopa monnieri supplementation has no effect on serum brain-derived neurotrophic factor levels but beneficially modulates nuclear factor kappa B and cyclic AMP response element-binding protein levels in healthy elderl
  12. Yaworski AM, Blyumin M, Chang T, Mammen AL, Greene M. Necrotizing myopathy with elevated anti-HMGCR antibodies following exposure to the supplement Bacopa. Muscle Nerve 2023;67(2):E1-E3.

See these in context on the Bacopa monograph →

Huperzine A 13 references
  1. Skolnick AA. Old Chinese herbal medicine used for fever yields possible new Alzheimer Disease therapy. JAMA 1997;277:776. DOI
  2. Ye JW, Cai JX, Wang LM, Tang XC. Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment. J Pharmacol Exp Ther 1999;288:814-9.. DOI
  3. Wang T, Tang XC. Reversal of scopolamine-induced deficits in radial maze performance by (-)-huperzine A: comparison with E2020 and tacrine. Eur J Pharmacol 1998;349:137-42. PubMed
  4. Xu SS, Gao ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao 1995;16:391-5.
  5. Zhang RW, Tang XC, Han YY, et al. [Drug evaluation of huperzine A in the treatment of senile memory disorders]. Chung Kuo Yao Li Hsueh Pao 1991;12:250-2.
  6. Xu SS, Cai ZY, Qu ZW, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao 1999;20:486-90.
  7. Felgenhauer N, Zilker T, Worek F, Eyer P. Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss. J Toxicol Clin Toxicol 2000;38:803-8.. PubMed
  8. Zhang, Z., Wang, X., Chen, Q., Shu, L., Wang, J., and Shan, G. [Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial]. Zhonghua Yi Xue Za Zhi 7-25-2002;82
  9. Cheng, D. H., Ren, H., and Tang, X. C. Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport 12-20-1996;8(1):97-101. PubMed
  10. Wang BS, Wang H, Wei ZH, Song YY, Zhang L, Chen HZ. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis. J Neural Transm (Vienna) 2009;116(4):457-65. PubMed
  11. Xu ZQ, Liang XM, Juan-Wu, Zhang YF, Zhu CX, Jiang XJ. Treatment with Huperzine A improves cognition in vascular dementia patients. Cell Biochem Biophys 2012;62(1):55-8. PubMed
  12. Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One 2013;8(9):e74916. PubMed
  13. Xing SH, Zhu CX, Zhang R, An L. Huperzine a in the treatment of Alzheimer's disease and vascular dementia: a meta-analysis. Evid Based Complement Alternat Med 2014;2014:363985. PubMed

See these in context on the Huperzine A monograph →

Lithium 26 references
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  3. Perlis RH, Sachs GS, Lafer B, et al. Effect of abrupt change from standard to low serum levels of lithium: a reanalysis of double-blind lithium maintenance data. Am J Psychiatry 2002;159:1155-9.. PubMed
  4. Pinelli JM, Symington AJ, Cunningham KA, Paes BA. Case report and review of the perinatal implications of maternal lithium use. Am J Obstet Gynecol 2002;187:245-9.. PubMed
  5. Sawagashira R, Sasagawa Y, Matsukura M, Takamaru Y. Case of myxedema coma induced by lithium carbonate in a patient with schizophrenia. Psychiatry Clin Neurosci. 2018;72(2):131. PubMed
  6. Foulser P, Abbasi Y, Mathilakath A, Nilforooshan R. Do not treat the numbers: lithium toxicity. BMJ Case Rep. 2017;2017. pii: bcr-2017-220079. PubMed
  7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017812s028,018421s027lbl.pdf. Accessed Nov. 21, 2018
  8. Fornaro M, Maritan E, Ferranti R, et al. Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes. Am J Psychiatry. 2020;177(1):76-92. DOI
  9. Rauf A, Gul S, Nasir M, Arif U, Oyenuga M. A Rare Case of Lithium-induced Partial Nephrogenic Diabetes Insipidus. Cureus. 2020;12(4):e7877. PubMed
  10. Hanna RM, Hasnain H, Sangalang MD, et al. Three Patients with Lithium-Associated Hyperparathyroidism: Literature Review Regarding Medical and Surgical Management. Case Rep Nephrol Dial. 2019;9(2):108-118. PubMed
  11. Rana P, Alba Aponte P, Babar G. An Adolescent Female with Bipolar Disorder Presenting with Lithium-Induced Hyperthyroidism. Case Rep Endocrinol. 2020;2020:1283464. PubMed
  12. Nwabufor PC, Omoniyi ON, Oyibo SO. A Case of Lithium-Associated Hypocalciuric Hypercalcemia. Cureus. 2020;12(9):e10606. PubMed
  13. Landa E, Wagner S, Makkar A, Liu A, Jung D. An atypical presentation of serotonin syndrome. Cureus. 2021;13(2):e13377. PubMed
  14. Benjelloun R, Motaib I, Otheman Y. Lithium-associated hypercalcemia presenting with neuropsychiatric manifestations in a patient with bipolar disorder. Case Rep Psychiatry. 2020;2020:6630838. PubMed
  15. Nombora O, Samico A, Venâncio Â. Lithium-Induced Dysgeusia and Hyposmia: A Case Report and a Literature Review. Clin Neuropharmacol 2023;46(1):31-33. PubMed
  16. Zhang P, Gandhi H, Kassis N. Lithium-induced nephropathy; One medication with multiple side effects: a case report. BMC Nephrol 2022;23(1):309. PubMed
  17. Kawada T. Lithium use and the risk of chronic kidney disease. Basic Clin Pharmacol Toxicol 2023;132(4):295-296. PubMed
  18. Yang Q, Cheng X, Su Z, Sun L, Li M. Electroconvulsive therapy combined with lithium developed reversible pure anomic aphasia: a case report. BMC Psychiatry 2022;22(1):663. PubMed
  19. Itoh M, Fukuya Y, Endo C, et al. Lithium carbonate-induced Stevens-Johnson syndrome: the first case report. Int J Dermatol 2023;62(3):e165-e167. PubMed
  20. Ono R, Nishiguchi S, Kitagawa I. Lithium intoxication-associated mild encephalitis/encephalopathy with a reversible splenial lesion: A case report. Bipolar Disord 2022;24(5):551-552. PubMed
  21. Li JJ, Tan S, Kawashita T, Tagle CA, Farmand F. Central Diabetes Insipidus in the Background of Lithium Use: Consider Central Causes Despite Nephrogenic as the Most Common. Am J Case Rep 2023;24:e939034. PubMed
  22. Yamada Y, Fujiwara M, Tsujino S, et al. Late-Onset Neutropenia With Clozapine Associated With Lithium Carbonate-Related Hyperthyroidism: A Case Report. J Clin Psychopharmacol 2023;43(1):76-77. PubMed
  23. Bocchetta A, Ambrosiani L, Sanna F, et al. Renal function at follow-up in a cohort of patients who had shown reduced glomerular filtration rate during long-term treatment with lithium. J Nephrol 2023;36(4):1079-1081. PubMed
  24. Sarangi A, Javed S, Paul T, Amor W. Lithium-Induced Sinoatrial Node Dysfunction. Cureus 2021;13(7):e16778. PubMed
  25. Aydin D, Tural Hesapcioglu S, Ceylan MF. Oropharyngeal Dysphagia as a Clinical Presentation of Lithium Intoxication: A Case Report. J Am Acad Child Adolesc Psychiatry 2021;60(12):1443-1445. PubMed
  26. Sogawa R, Tobita S, Monji A, et al. Deep Vein Thrombosis after Lithium Toxicity: A Report of Two Cases and Literature Review. Case Rep Psychiatry 2021;2021:9934037. PubMed

See these in context on the Lithium monograph →

Gotu Kola 18 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Pointel JP, Boccalon H, Cloarec M, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiol 1987;38:46-50. PubMed
  3. Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the east Asian medical plant Centella asiatica. Phytomedicine 2000;7:427-48.
  4. Eun HC, Lee AY. Contact dermatitis due to madecassol. Contact Dermatitis 1985;13:310-3.. PubMed
  5. Hausen BM. Centella asiatica (Indian pennywort), an effective therapeutic but a weak sensitizer. Contact Dermatitis 1993;29:175-9..
  6. Bilbao I, Aguirre A, Zabala R, et al. Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella asiatica extract. Contact Dermatitis 1995;33:435-6.
  7. Cesarone MR, Incandela L, De Sanctis MT, et al. Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model. Angiology 2001;52 Suppl 2 DOI
  8. Bradwejn J, Zhou Y, Koszycki D, Shlik J. A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol 2000;20:680-4. PubMed
  9. Young GL, Jewell D. Creams for preventing stretch marks in pregnancy. Cochrane Database Syst Rev 2000;(2):CD000066. PubMed
  10. Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 2005;97:115-24. PubMed
  11. Mallol J, Belda MA, Costa D, et al. Prophylaxis of striae gravidarum with a topical formulation. A double blind trial. Int J Cosmet Sci 1991;3:51-7.
  12. Izu, R., Aguirre, A., Gil, N., and Diaz-Perez, J. L. Allergic contact dermatitis from a cream containing Centella asiatica extract. Contact Dermatitis 1992;26(3):192-193.
  13. Santucci, B., Picardo, M., and Cristaudo, A. Contact dermatitis due to Centelase. Contact Dermatitis 1985;13(1):39. PubMed
  14. Vena, G. A. and Angelini, G. Contact allergy to Centelase. Contact Dermatitis 1986;15(2):108-109. PubMed
  15. Marastoni, F., Baldo, A., Redaelli, G., and Ghiringhelli, L. [Centella asiatica extract in venous pathology of the lower limbs and its evaluation as compared with tribenoside]. Minerva Cardioangiol. 1982;30(4):201-207.
  16. Danese, P., Carnevali, C., and Bertazzoni, M. G. Allergic contact dermatitis due to Centella asiatica extract. Contact Dermatitis 1994;31(3):201.
  17. Bilbao, I., Aguirre, A., Zabala, R., Gonzalez, R., Raton, J., and Diaz Perez, J. L. Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella asiatica extract. Contact Dermatitis 1995;33(6):435-436.
  18. Dantuluri S, North-lewis P, Karthik SV. Gotu Kola induced hepatotoxicity in a child - need for caution with alternative remedies. Dig Liver Dis. 2011;43(6):500. PubMed

See these in context on the Gotu Kola monograph →

Yucca 3 references
  1. <p><span>Kanerva, L., Estlander, T., Petman, L., Makinen-Kiljunen, S. Occupational allergic contact urticaria to yucca (Yucca aloifolia), weeping fig (Ficus benjamina), and spathe flower (Spathiphyllum wallisii). Allergy. 2001;56(10): 1008-11.</span></p>
  2. Poljacki, M., Paravina, M., Jovanovic, M., Subotic, M., and Duran, V. [Contact allergic dermatitis caused by plants]. Med Pregl. 1993;46(9-10):371-375.
  3. Mahillon, V., Saussez, S., and Michel, O. High incidence of sensitization to ornamental plants in allergic rhinitis. Allergy 2006;61(9):1138-1140. PubMed

See these in context on the Yucca monograph →

Phosphatidylserine 9 references
  1. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull 1992;28:61-6.
  2. Pepping J. Phosphatidylserine. Am J Health-Syst Pharm 1999;56:2038,2043-4.
  3. Kidd PM. Phosphatidylserine; Membrane nutrient for memory. A clinical and mechanistic assessment. Altern Med Rev 1996;1:70-84.
  4. Kim HY, Akbar M, Lau A, et al. Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3). Role of phosphatidylserine in antiapoptotic effect. J Biol Chem 2000;275:35215-23.. PubMed
  5. Zanotti A, Valzelli L, Toffano G. Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. Psychopharmacology (Berl) 1989;99:316-21.. PubMed
  6. Schreiber S, Kampf-Sherf O, Gorfine M, et al. An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37:302-7.
  7. Pepping, J. Phosphatidylserine. Am J Health Syst.Pharm. 10-15-1999;56(20):2038, 2043-2038, 2044.
  8. Monteverde, A., Gnemmi, P., Rossi, F., Monteverde, A., and Finali, G. C. Selegiline in the treatment of mild to moderate Alzheimer-type dementia. Clin.Ther 1990;12(4):315-322.
  9. Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geri PubMed

See these in context on the Phosphatidylserine monograph →

Vinpocetine 27 references
  1. Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol 1991;6:31-43. PubMed
  2. Balestreri R, Fontana L, Astengo F. A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. J Am Geriatr Soc 1987;35:425-30. PubMed
  3. Akopov SE, Gabrielian ES. Effects of aspirin, dipyridamole, nifedipine and cavinton which act on platelet aggregation induced by different aggregating agents alone and in combination. Eur J Clin Pharmacol 1992;42:257-9. PubMed
  4. Kidd PM. A review of nutrients and botanicals in the integrative management of cognitive dysfunction. Altern Med Rev 1999;4:144-61..
  5. Wollschlaeger B. Efficacy of vinpocetine in the management of cognitive impairment and memory loss. JANA 2001;4:25-30.
  6. Hitzenberger G, Sommer W, Grandt R. Influence of vinpocetine on warfarin-induced inhibition of coagulation. Int J Clin Pharmacol Ther Toxicol 1990;28:323-8..
  7. Dekoninck, W. J., Jocquet, P., Jacquy, J., and Henriet, M. Comparative study of the clinical effects of vincamine + glycerol versus glycerol + placebo in the acute phase of stroke. Arzneimittelforschung. 1978;28(9):1654-1657.
  8. Fischhof, P. K., Moslinger-Gehmayr, R., Herrmann, W. M., Friedmann, A., and Russmann, D. L. Therapeutic efficacy of vincamine in dementia. Neuropsychobiology 1996;34(1):29-35. PubMed
  9. Feher, G., Koltai, K., Kesmarky, G., Horvath, B., Toth, K., Komoly, S., and Szapary, L. Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases. Phytomedicine. 2009;16(2-3):111-117. PubMed
  10. Kuzuya, F. Effects of vinpocetine on platelet aggregability and erythrocyte deformability. Ther Hung. 1985;33(1):22-34.
  11. Kovacs, L. Cavinton in the treatment of acute stroke. Ther Hung. 1985;33(1):50-57.
  12. Osawa, M. and Maruyama, S. Effects of TCV-3B (vinpocetine) on blood viscosity in ischemic cerebrovascular diseases. Ther.Hung. 1985;33(1):7-12.
  13. Ebi, O. Open-labeled phase III clinical trials with vinpocetine in Japan. Ther.Hung. 1985;33(1):41-49.
  14. Richichi, I., Valsecchi, O., Falcone, C., Sofi, A., and Zanini, L. [A case of "torsade de pointe" during vincamine therapy]. Minerva Cardioangiol. 1978;26(3):197-200.
  15. Dany, F., Merle, L., Goudoud, J. C., Liozon, F., Blanc, P., Bouvot, J. C., Nicot, G., and Dangoumau, J. [Cardiac toxicity of vincamine: a seven cases report of ventricular arrhythmias by parenteral administration of vincamine (author's transl)]. Therapie
  16. Fenzl, E., Apecechea, M., Schaltenbr, R., and Fridel, R. Long term study concerning tolerance and efficacy of vinpocetine in elderly patients suffering from a mild to moderate organic psychosyndrome. Senile dementia: early detection 1986;580-585.
  17. Peruzza, M. and DeJacobis, M. A double-blind placebo controlled evaluation of the efficacy and safety of vinpocetine in the treatment of patients with chronic vascular or degenerative senile cerebral dysfunction. ADV THER 1986;3(4):201-209.
  18. Manconi, E., Binaghi, F., and Pitzus, F. A double-blind clinical trial of vinpocetine in the treatment of cerebral insufficiency of vascular and degenerative origin. CURR THER RES, CLIN EXP 1986;40(4):702-709.
  19. Blaha, L., Erzigkeit, H. L., Adamczyk, L. A., Freytag, L. S., and Schaltenbrand, R. Clinical evidence of the effectiveness of vinpocetine in the treatment of organic psychosyndrome. Human Psychopharmacology: Clinical & Experimental 1989;4(2):103-111. DOI
  20. Shimizu, Y., Saitoh, K., Nakayama, M., Suto, K., Daikohara, R., and Nemoto, T. Agranulocytosis induced by vinpocetine. Medicine On-line 2011;
  21. Kong L, Song C, Ye L, et al. The Effect of Vinpocetine on Human Cytochrome P450 Isoenzymes by Using a Cocktail Method. Evid Based Complement Alternat Med. 2016;2016:5017135. PubMed
  22. Vinpocetine in Dietary Supplements. FDA Food/Dietary Supplements/Products & Ingredients. Available at: http://www.fda.gov/Food/DietarySupplements/ProductsIngredients/ucm518478.htm. Accessed 6 September 2016.
  23. Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine. FDA Food/Dietary Supplements/Products & Ingredients. Available at: https://www.fda.gov/news-events/press-announcements/statement-
  24. Zhang W, Huang Y, Li Y, et al. Efficacy and safety of vinpocetine as part of treatment for acute cerebral infarction: A randomized, open-label, controlled, multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) trial. Clin Drug Investig 2016; PubMed
  25. National Toxicology Program. NTP technical report on the prenatal development toxicity studies of vinpocetine (CAS No. 42971-09-5) in Sprague Dawley Rats and New Zealand White Rabbits (Gavage Studies). Research Triangle Park, NC: National Toxicology Progr
  26. Gutiérrez-Farfán I, Reyes-Legorreta C, Solís-Olguín M, Alatorre-Miguel E, Verduzco-Mendoza A, Durand-Rivera A. Evaluation of vinpocetine as a therapy in patients with sensorineural hearing loss: a phase II, open-label, single-center study. J Pharmacol Sci PubMed
  27. Hu X, Guo K, Li J, et al. Postoperative ecchymoma of eyelid after botulinum toxin injection for hemifacial spasm: a case report. Front Neurol 2023;14:1171303. PubMed

See these in context on the Vinpocetine monograph →

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Supplement interaction checker › Check any supplement or product against your medications Drug–drug interactions › Check two or more of your medications against each other Browse medications A–Z › Every drug we've checked against herbs & supplements NDC & pricing lookup › Find a drug’s NDCs, packaging and costs Ask a pharmacist › Free, personal answer from our licensed team