Major interaction on record — check this product against your medications before combining. Based on 41 of 65 ingredients. Check your meds →
Dietary supplement

Limitless Mind Ingredients & Drug Interactions

by Lean Factor

Limitless Mind label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Limitless Mind 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

Limitless Mind is a dietary supplement by Lean Factor with 65 active ingredients. Its ingredients are commonly taken for stress and anxiety, sleep problems, fatigue and low energy.Based on those ingredients, 1,926 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Ashwagandha Root Extract, Rhodiola Root Extract, Ginkgo biloba Leaf Extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Limitless Mind by Lean Factor

Ask about any prescription or over-the-counter medication and we check it for interactions with Limitless Mind by Lean Factor — 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.

HelloPharmacist Scorecard of Limitless Mind by Lean Factor

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Aug 20, 2026

What’s inside

Partial disclosure
Ingredient Transparency · database check
Partial

Most active ingredients list an amount, but at least one is hidden in a blend or missing.

Why this rating?
  • The label discloses an exact amount for 70 of its 78 active ingredients.
  • “Vitamin B12” is listed as a grouped ingredient — the label gives one combined amount (1,000 mcg) without saying how much of each component you get.
  • “Ginkgo biloba Leaf Extract” is listed as a grouped ingredient — the label gives one combined amount (100 mg) without saying how much of each component you get.
  • “Ashwagandha Root Extract” is listed as a grouped ingredient — the label gives one combined amount (35 mg) without saying how much of each component you get.

Limitless Mind contains 78 ingredients, of which we've reviewed interaction data for many of the active vitamins and herbal extracts. The product includes B vitamins (B1, B2, B6, B12 as methylcobalamin), vitamin C, vitamin D3, niacin, iodine, and zinc for foundational nutrition.

It also contains amino acids, the herbal extract L-tyrosine, 5-hydroxytryptophan (5-HTP) for mood support, L-theanine for cognitive calm, and ashwagandha, rhodiola, and eleuthero root extracts as adaptogens—plant compounds that may help the body manage stress. Pregnenolone is included as a hormone precursor, and theobromine (from cocoa) adds a mild stimulant.

Silica, ginkgo biloba extract, and other plant polysaccharides round out the formula. The capsules contain cellulose and maltodextrin as inactive ingredients.

Does it work?

Moderate evidence
Evidence for Intended Use · database check
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
Moderate

Some clinical evidence supports this product's ingredients for its stated purpose, but it isn't conclusive.

Why this rating?
  • The label markets this product for: improve cognitive function and brain health.
  • We looked for evidence on: Age-related cognitive decline, Alzheimer disease, memory decline, mental performance, age-related dementia.
  • The strongest evidence on file: Ginkgo is rated "Possibly Effective" for Dementia (Natural Medicines).
  • Also on file: Huperzine A is rated "Possibly Effective" for Alzheimer disease.
  • Also on file: Acetyl-l-carnitine is rated "Possibly Effective" for Age-related cognitive decline, Alzheimer disease.

The data we hold shows effectiveness ratings for only some ingredients. Vitamin D3 is effective for bone health conditions (rickets, osteomalacia).

Niacin is likely effective for HIV-related lipid problems and possibly effective for metabolic syndrome. Vitamin C is effective for vitamin C deficiency and possibly effective for exercise-related respiratory infections and cataracts.

L-tyrosine is effective for PKU and possibly effective for cognitive function and memory. Vitamin B6 is effective for certain types of anemia and deficiency, and possibly effective for pregnancy-related nausea.

Iodine is likely effective for iodine deficiency and radiation protection. Zinc is effective for zinc deficiency and possibly effective for acne and age-related macular degeneration.

Theobromine (cocoa) is possibly effective for cardiovascular health. For 5-HTP, L-theanine, and pregnenolone, effectiveness ratings in our data range from insufficient evidence to possibly ineffective for most stated uses—the evidence isn't established for cognitive or mood claims specific to this product.

The evidence, ingredient by ingredient Ashwagandha Eleuthero Rhodiola Shilajit Schisandra Deer Velvet Silicon Vitamin D

How safe is it?

Well-documented data
Safety Information · database check
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 31 of the 35 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 33 of 35.
  • General safety write-ups exist for 35 of 35.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most of these ingredients are generally well tolerated at normal doses. Vitamin D3 is safe at recommended levels but can cause toxicity at very high doses; pregnancy use requires medical guidance.

Niacin can cause flushing, liver problems, and elevated blood sugar at high doses. Vitamin C is safe orally but high doses may cause kidney stones in susceptible people.

L-tyrosine is generally well tolerated but lacks long-term safety data and should be discussed with a healthcare provider. Vitamin B6 is safe below 100 mg daily; very high doses over time can harm nerves.

Iodine is safe at normal dietary amounts but high doses can cause thyroid problems—some iodine is needed in pregnancy, but avoid excess. 5-HTP may cause drowsiness, nausea, and diarrhea, and is best avoided during pregnancy and breastfeeding due to insufficient safety data.

L-theanine is generally well tolerated short-term but lacks long-term data; avoid in pregnancy and breastfeeding. Zinc is safe within recommended limits but high doses can increase copper deficiency risk.

Theobromine (cocoa) contains caffeine and is generally safe in food amounts. Phenylethylamine and pregnenolone have limited human safety data and should be used only under professional guidance.

Pregnancy and breastfeeding safety varies by ingredient—talk with your doctor or pharmacist about your individual situation.

Side effects, ingredient by ingredient Ashwagandha Eleuthero Rhodiola Shilajit Schisandra Deer Velvet Silicon Vitamin D

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

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

Why this rating?
  • 30 of the 35 matched ingredients can interact with medications — Iodine, Pregnenolone, Ginkgo, Turmeric, Huperzine A, 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: 1,926 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.

Before taking Limitless Mind, check with your doctor or pharmacist if you take any of the following: blood pressure medications (antihypertensives)—theanine and cocoa may lower pressure further; diabetes drugs—niacin can raise blood sugar; cholesterol medications (statins or atorvastatin)—niacin and vitamin D may affect them; blood thinners (warfarin) or anticoagulants—vitamin C and niacin may reduce effectiveness; heart rhythm medications (verapamil, diltiazem, digoxin)—vitamin D may interfere; seizure drugs (phenobarbital, phenytoin)—vitamin B6 at high doses may lower levels; antibiotics (quinolones, tetracyclines, cephalexin)—zinc will reduce absorption; gout medications (allopurinol, probenecid)—niacin may counteract them; antidepressants or serotonergic drugs—5-HTP and phenylethylamine increase serotonin effects; levodopa for Parkinson's—L-tyrosine and vitamin B6 may interfere; thyroid medication (levothyroxine) or antithyroid drugs—vitamin C, iodine, and L-tyrosine may affect them; HIV medications (integrase inhibitors, ritonavir, bictegravir combinations)—zinc may reduce levels; lithium—iodine may increase risk of low thyroid function; metformin—methylcobalamin interaction…

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glancePartially disclosed formula with some supporting evidence for its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

Limitless Mind is a complex multi-ingredient formula aimed at cognitive and mood support, with several B vitamins, vitamin D, minerals, and herbal adaptogens. Because it contains 14 ingredients with documented interactions affecting over 1,900 individual medications, it's critical you check your exact prescriptions before starting—especially if you take blood pressure drugs, diabetes or cholesterol medications, blood thinners, seizure drugs, or antibiotics.

Pregnancy and breastfeeding require individual assessment given the variety of ingredients and their safety data. Talk with your own doctor or pharmacist before you start this product to make sure it's right for you and won't conflict with what you're already taking.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 36 of 78 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Dec 14, 2023.

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 Limitless Mind, straight from the product label.

Brand Lean Factor
Barcode (UPC) 309272872965
Net contents 115 Capsule(s)
Market status On market
Date entered into DSLD Dec 14, 2023
DSLD ID 299857
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), No Allergies, 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 Limitless Mind by Lean Factor, 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:
1 Capsule(s)
Maximum serving Sizes:
10 Capsule(s)
Servings per container
23
UPC/BARCODE
309272872965
IngredientAmount% DV
Vitamin B121000 mcg41670%
Silica0 NP--
Vitamin D325 mcg125%
Niacin40 mg250%
Vitamin C90 mg100%
L-Tyrosine150 mg--
Vitamin B610 mg590%
Iodine75 mcg50%
5-Hydroxytryptophan80 mg--
L-Theanine250 mg--
Zinc2.2 mg20%
Theobromine80 mg--
Ginkgo biloba Leaf Extract100 mg--
Amino Acids0 NP--
Polysaccharides30 mg--
Vitamin B21.3 mg100%
Vitamin B1100 mg8375%
Phenylethylamine30 mg--
Pregnenolone30 mg--
Methylcobalamin500 mcg--
Rosmarinic Acid10 mg--
Ashwagandha Root Extract35 mg--
Rosavins1.2 mg--
Eleuthero Root Extract200 mg--
Rhodiola Root Extract40 mg--
Folate600 mcg150%
Salidrosides0.4 mg--
Antioxidants0 NP--
Polyphenols0 NP--
Fucoxanthin8 mg--
Rosemary Leaf Extract150 mg--
Fulvic Acid50 mg--
Adenosylcobalamin500 mcg--
Withanolides3.5 mg--
Shilajit extract100 mg--
Flavonoids0 NP--
Fucoidan68 mg--
Lion's Mane Mushroom Extract150 mg--
Centrophenoxine40 mg--
Phosphatidylserine100 mg--
Docosahexaenoic Acid14 mg--
Ionic Trace Minerals100 mg--
Uridine 5'-Monophosphate50 mg--
Trace Minerals0 NP--
Coenzyme Q-1050 mg--
Pyrroloquinoline Quinone Disodium Salt26 mg--
Nicotinamide Mononucleotide20 mg--
Acetyl L-Carnitine Arginate DiHCl150 mg--
Vitamin B510 mg200%
AdaptoBalance Proprietary Blend455 mg--
Eleutheroside E1 mg--
Eleutheroside B3 mg--
Schizandrins3 mg--
Korean Red Ginseng Root Extract35 mg--
VasoBlast Proprietary Blend693 mg--
Sodium Nitrite50 mg--
Magnesium12.6 mg3%
Kanna Leaf Extract50 mg--
L-Dihydroxyphenylalanine80 mg--
Coleus forskohlii400 mg--
NutriAbsorb Proprietary Blend47 mg--
Gingerols5 mg--
Glycyrrhizin5 mg--
Piperine12 mg--
Fulvic Mineral Complex25 mg--
Flavonoids & Terpenoids0 NP--
Organic Acids0 NP--
Terpene Lactones6 mg--
Theacrine80 mg--
Ginkgo Flavone Glycosides24 mg--
Terpenoid0 NP--
Huperzine A100 mcg--
L-Ergothioneine1 mg--
Schizandra extract35 mg--
Pantael10 mg--
Ginsenoside14 mg--
NeuroPrime Proprietary Blend2735 mg--
Fullerene1 mg--
Celangulin A3 mg--
Silk Protein, Hydrolysate100 mg--
Asiaticoside20 mg--
Citicoline150 mg--
Carnosic Acid10 mg--
Salvianolic Acid B20 mg--
Spermidine2 mg--
Methyliberine80 mg--
Ecklonia cava extract80 mg--
Lithium4 mg--
Pterostilbene100 mg--
Fisetin28 mg--
Curcumin100 mg--
Bacopasides75 mg--
Alpha-Glycerylphosphorylcholine150 mg--
7,8-Dihydroxyflavone15 mg--
Hericenones3 mg--

Other ingredients: Cellulose, 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.
Suggested/Recommended/Usage/Directions

Suggested Use: As a dietary supplement, take up to 5 capsules with water first thing in the morning before eating. If stomach discomfort occurs, take with breakfast. Adjust dosage for the desired effect, but do not take more than 10 capsules in a day. Use with caffeine may enhance effects. For best results, cycle by taking for 5 days on and 2 days off each week.

Formulation

Does not contain: GMOs, artificial colors, fillers, preservatives, gluten, yeast, milk, soy, tree nuts, fish, wheat, sesame, eggs, dairy, shellfish, or peanuts.

At therapeutic concentrations, this nootropic formulation is specifically developed to improve cognitive function. With powerful circulation enhancers and bioenhancers, Limitless Mind is the most potent brain boosting formula available.

Proudly made in the U.S.A. with carefully selected ingredients of domestic & international origin. Heightens creativity Promote mental clarity Amplify willpower Lift brain fog Accelerate thinking Brain revitalizer Fuel focus & concentration

Formula

Limitless Mind is a proprietary, ultra-premium, scientifically-validated adaptogenic herbal blend containing 64 potent active ingredients.

Precautions

Warning: Use only as directed.

Do not take with psychiatric medication, alcohol, or recreational drugs, or if you are sensitive to stimulants, under 18 years old, pregnant or nursing, have phenylketonuria, taking an MAO inhibitor or SSRI, or experience any uncomfortable symptoms.

Do not take with psychiatric medication, alcohol, or recreational drugs, or if you are sensitive to stimulants, under 18 years old, pregnant or nursing, have phenylketonuria, taking an MAO inhibitor or SSRI, or experience any uncomfortable symptoms.

FDA Disclaimer Statement

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

Seals/Symbols

GMP Good Manufacturing Practice Compliant Clinically Proven

General Statements

100% Customer Satisfaction Guaranteed

120 Day Money Back Guarantee

FDA Statement of Identity

Clinical Strength Herbal Supplement

Brand IP Statement(s)

Albion and TRAACS are registered trademarks of Albion Laboratories, Inc.

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

See for yourself

Limitless Mind by Lean Factor label

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

Limitless Mind 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 Limitless Mind by Lean Factor

These are the 65 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Capsule(s) Dosage formCapsule Servings per container23 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.

AdaptoBalance Proprietary Blend

455 mg per serving

VasoBlast Proprietary Blend

693 mg per serving

NutriAbsorb Proprietary Blend

47 mg per serving
  • › Gingerols
  • › Glycyrrhizin
  • › Piperine
  • › Fulvic Mineral Complex

NeuroPrime Proprietary Blend

2735 mg per serving

Other (inactive) ingredients: Cellulose, Maltodextrin. These complete the product’s ingredient list but are not active constituents.

Interaction report

Limitless Mind by Lean Factor Drug Interactions

Want to check YOUR meds against Limitless Mind?

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
1,926Drugs
295 Major 1,626 Moderate 5 Minor

Ingredients driving the most interactions

Ashwagandha Root Extract 1,372
Rhodiola Root Extract 1,271
Ginkgo biloba Leaf Extract 1,266
Eleuthero Root Extract 1,140
Curcumin 1,133

Individual Drug Interactions

The ingredients in Limitless Mind interact with 1,926 drugs. Click any drug to see the details.

36 of the 65 ingredients in Limitless Mind interact with drugs. Each result below shows which ingredient is responsible. Ashwagandha Root Extract Rhodiola Root Extract Ginkgo biloba Leaf Extract Eleuthero Root Extract Curcumin Piperine Coleus forskohlii Schizandra extract Niacin Vitamin D3 Theobromine L-Theanine Lithium 5-Hydroxytryptophan Rosemary Leaf Extract Lion's Mane Mushroom Extract Magnesium Kanna Leaf Extract Theacrine Phosphatidylserine Huperzine A Vitamin B6 Vitamin C Sodium Nitrite Acetyl L-Carnitine Arginate DiHCl Coenzyme Q-10 Phenylethylamine Shilajit extract Pregnenolone Zinc Pantael L-Tyrosine Vitamin B12 Vitamin B2 Alpha-Glycerylphosphorylcholine Iodine

Each ingredient & the kinds of drugs it affects

For each ingredient in Limitless Mind 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.

Ashwagandha Root Extract10 drug types · 1,372 drugs

Antidiabetes Drugs

Theoretically, taking ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.
There is preliminary clinical evidence suggesting that ashwagandha might lower blood glucose levels. Theoretically, ashwagandha might have additive effects when used with antidiabetes drugs and increase the risk of hypoglycemia.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.
Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure. Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.

Likelihood Possible Evidence D
Benzodiazepines

Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.
There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin). This may also occur with other benzodiazepines.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.
Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.
Ashwagandha has been linked to cases of acute hepatitis, liver failure, hepatic encephalopathy, autoimmune hepatitis, the need for liver transplantation, and death due to liver failure.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.
Ashwagandha has demonstrated immunostimulant effects in humans. Animal research has shown that ashwagandha can attenuate the immunosuppression caused by cyclophosphamide.

Likelihood Possible Evidence D
Thyroid Hormone

Ashwagandha might increase the effects and adverse effects of thyroid hormone.
Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion. In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism.

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

Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that ashwagandha extract induces CYP1A2 enzymes.

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

Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that ashwagandha extract induces CYP3A4 enzymes.

Likelihood Possible Evidence D
Serotonergic Drugs

Some animal studies have reported that ashwagandha can enhance serotonergic transmission by altering certain serotonin (5-HT) receptors. However, there is no evidence to suggest that ashwagandha increases the risk of serotonin-related effects, and there have been no published case reports of serotonin syndrome when combined with other serotonergic drugs. Nevertheless, due to the lack of extensive studies on the matter and the fact that ashwagandha appears to affect serotonergic pathways, it would be prudent to exercise caution when combining it with drugs that affect serotonin. [References: - Effects of Withania somnifera (Ashwaga ndha) on Stress and the Stress-Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Curr Neuropharmacol. 2021 Sep 14; 19: 1468–1495. - A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573577/]

Likelihood Possible Evidence C
Ashwagandha Root Extract full monograph & interactions

Rhodiola Root Extract10 drug types · 1,271 drugs

Antidiabetes Drugs

Theoretically, taking rhodiola with antidiabetes drugs might increase the risk of hypoglycemia.
In vitro and animal research shows that rhodiola extract can decrease blood glucose due to alpha-glucosidase activity.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking rhodiola with antihypertensive drugs might increase the risk of hypotension.
In vitro and animal research shows that rhodiola extract inhibits angiotensin-converting enzyme (ACE) and might lower blood pressure.

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

Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.
In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied. Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours.

Likelihood Possible Evidence B
Immunosuppressants

Theoretically, rhodiola use might interfere with immunosuppressive therapy.
In vitro and animal research show that rhodiola has immunostimulatory effects.

Likelihood Possible Evidence D
Losartan (Cozaar)

Rhodiola might increase the levels and adverse effects of losartan.
A clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

Theoretically, rhodiola might increase levels of P-glycoprotein substrates.
In vitro research shows that rhodiola inhibits P-glycoprotein. Theoretically, using rhodiola with P-glycoprotein substrates might increase drug levels and potentially increase the risk of adverse effects.

Likelihood Possible Evidence D
Antidepressant Drugs

Theoretically, rhodiola might increase the risk of adverse effects when taken with antidepressants.
A review of adverse event reports in Poland identified cases of tachyarrhythmias, myalgia, arthralgia, gum pain, restless leg syndrome, swallowing disorders, and changes in consciousness when rhodiola was taken in combination with paroxetine, escitalopram, fluoxetine, sertraline, trazodone, and/or duloxetine.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, rhodiola might increase the risk of adverse effects when taken with CNS depressants.
A review of adverse event reports in Poland identified cases of excessive sedation, myoclonus, hypotension, and hallucinations when rhodiola was taken with haloperidol, diazepam, or alprazolam.

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

Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate.

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

Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that rhodiola inhibits CYP3A4. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate.

Likelihood Possible Evidence B
Rhodiola Root Extract full monograph & interactions

Ginkgo biloba Leaf 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 biloba Leaf Extract full monograph & interactions

Eleuthero Root 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 Root Extract full monograph & interactions

Curcumin24 drug types · 1,133 drugs

Alkylating Agents

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression. However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

Likelihood Possible Evidence D
Amlodipine (Norvasc)

Taking turmeric with amlodipine may increase levels of amlodipine.
Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone. Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro. Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk. It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes. Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction. Other clinical studies in patients with diabetes show that taking curcumin daily can reduce blood glucose levels when compared with placebo.

Likelihood Possible Evidence B
Antitumor Antibiotics

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65%. However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

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

Turmeric might increase or decrease levels of drugs metabolized by CYP3A4.
In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4. Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib. In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition.
Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. An animal model suggests that induction of CYP3A4 occurs after daily curcumin use for 1 week. However, the induction of CYP3A4 by turmeric has not been reported in humans.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.
There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.
In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity.

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

Theoretically, turmeric might increase blood levels of OATP4C1 substrates.
In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs. Theoretically, taking turmeric might decrease renal excretion of OATP substrates.

Likelihood Possible Evidence D
Sulfasalazine (Azulfidine)

Turmeric might increase the effects and adverse effects of sulfasalazine.
Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

Turmeric might increase the effects and adverse effects of tacrolimus.
In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition. In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4.

Likelihood Possible Evidence D
Talinolol

Turmeric may reduce the absorption of talinolol in some situations.
Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day. The clinical significance of this effect is unclear.

Likelihood Probable Evidence B
Tamoxifen (Nolvadex)

Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.
In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers.

Likelihood Possible Evidence B
Topoisomerase I Inhibitors

Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71%. However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effect, if any, turmeric might have.

Likelihood Possible Evidence D
Tramadol (Ultram)

Theoretically, turmeric might increase or decrease levels of tramadol.
Animal research suggests that a single dose of curcumin, a constituent of turmeric, may increase tramadol's maximum concentration (Cmax) by inhibiting metabolism, while continued daily use for 7 days may reduce the area under the curve (AUC) due to the induction of drug-metabolizing enzymes such as cytochrome P450 3A4 (CYP3A4). However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Turmeric might increase the risk of bleeding with warfarin.
One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10. Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro, which may produce additive effects when taken with warfarin.

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

Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.
In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2. However, other in vitro research suggests that curcumin does not significantly affect CYP1A2.

Likelihood Possible Evidence D
Docetaxel (Taxotere)

Theoretically, turmeric might increase blood levels of oral docetaxel.
Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel. However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

Likelihood Possible Evidence D
Estrogens

Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.
In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors.

Likelihood Possible Evidence D
Glyburide (Diabeta, Others)

Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.
Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research.

Likelihood Possible Evidence B
Losartan (Cozaar)

Theoretically, turmeric might increase the effects of losartan.
Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan.

Likelihood Possible Evidence D
Norfloxacin (Noroxin)

Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.
Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.
In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity.

Likelihood Possible Evidence D
Paclitaxel (Abraxane, Onxol)

Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.
Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant. Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel. However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

Likelihood Possible Evidence D
Curcumin 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

Coleus forskohlii7 drug types · 915 drugs

Calcium Channel Blockers

Theoretically, combining coleus with calcium channel blockers might increase the coronary vasodilatory effects.
Forskolin, a constituent of coleus, and calcium channel blockers both cause coronary vasodilatory effects.

Likelihood Probable Evidence B
Nitrates

Theoretically, combining coleus with nitrates might increase the coronary vasodilatory effects.
Forskolin, a constituent of coleus, and nitrates both cause coronary vasodilatory effects.

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, concomitant use of coleus and anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.
In vitro and animal research shows that forskolin, a constituent of coleus, can inhibit platelet aggregation and adhesion.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, combining coleus with antihypertensive drugs might cause additive blood pressure lowering effects and increase the risk of hypotension.
Animal research shows that forskolin, a constituent of coleus, may lower blood pressure.

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

Theoretically, taking coleus may affect drugs metabolized by CYP2C9 and increase the risk of adverse effects or reduce the effectiveness.
Research on the effect of coleus on CYP2C9 is conflicting. Some animal research shows that coleus extract can induce CYP2C9, while in vitro research shows that coleus can inhibit CYP2C9. Until more is known, advise patients that taking coleus might increase or decrease levels of drugs metabolized by CYP2C9.

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

Theoretically, taking coleus might decrease serum levels of drugs metabolized by CYP3A4.
In vitro research shows that coleus can activate 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 coleus and other drugs affected by these enzymes.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, taking coleus may affect the metabolism of warfarin and increase the risk of adverse effects or reduce the effectiveness.
Some animal research shows that coleus extract can induce cytochrome P450 2C9 (CYP2C9), an enzyme that metabolizes warfarin. However, other in vitro research shows that coleus can inhibit CYP2C9. Theoretically, taking coleus with drugs metabolized by CYP2C9 might affect drug levels and the risk of adverse effects. Until more is known, advise patients that taking coleus might increase or decrease levels of warfarin.

Likelihood Possible Evidence D
Coleus forskohlii full monograph & interactions

Schizandra 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
Schizandra extract 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

Vitamin D38 drug types · 715 drugs

Aluminum

Vitamin D might increase aluminum absorption and toxicity, but this has only been reported in people with renal failure.
The protein that transports calcium across the intestinal wall can also bind and transport aluminum. This protein is stimulated by vitamin D, which may therefore increase aluminum absorption. This mechanism may contribute to increased aluminum levels and toxicity in people with renal failure, when they take vitamin D and aluminum-containing phosphate binders chronically.

Likelihood Probable Evidence B
Atorvastatin (Lipitor)

Vitamin D might reduce absorption of atorvastatin.
A small, low-quality clinical study shows that taking vitamin D reduces levels of atorvastatin and its active metabolites by up to 55%. However, while atorvastatin levels decreased, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels did not substantially change. Atorvastatin is metabolized in the gut by CYP3A4 enzymes, and researchers theorized that vitamin D might induce CYP3A4, causing reduced levels of atorvastatin. However, this proposed mechanism was not specifically studied.

Likelihood Probable Evidence B
Calcipotriene (Dovonex)

Taking calcipotriene with vitamin D increases the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with vitamin D supplements might increase the risk of hypercalcemia.

Likelihood Probable Evidence D
Digoxin (Lanoxin)

Theoretically, hypercalcemia induced by high-dose vitamin D can increase the risk of arrhythmia from digoxin.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and digoxin concurrently.

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

Theoretically, hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of diltiazem for arrhythmia.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically this could also occur with diltiazem. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and diltiazem concurrently.

Likelihood Probable Evidence B
Thiazide Diuretics

Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily.

Likelihood Probable Evidence D
Verapamil (Calan, Others)

Hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of verapamil for arrhythmia.
Hypercalcemia due to high doses of vitamin D can reduce the effectiveness of verapamil in atrial fibrillation. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.

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

Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.

Likelihood Possible Evidence D
Vitamin D3 full monograph & interactions

Theobromine37 drug types · 661 drugs

Ace Inhibitors (Aceis)

Theoretically, taking cocoa with ACEIs might increase the risk of adverse effects.
Human research shows that dark chocolate can inhibit ACE. Additionally, prolonged angioedema in an elderly patient on an ACE inhibitor was precipitated with intake of diabetic chocolate.

Likelihood Possible Evidence D
Adenosine (Adenocard)

Theoretically, cocoa might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Cocoa contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not 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 than adenosine-induced stress testing.

Likelihood Possible Evidence B
Alcohol (Ethanol)

Theoretically, concomitant use might increase levels and adverse effects of caffeine.
Cocoa contains caffeine. Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, cocoa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research shows that intake of cocoa can inhibit platelet adhesion, aggregation, and activity and increase aspirin-induced bleeding time. For patients on dual antiplatelet therapy, cocoa may enhance the inhibitory effect of clopidogrel, but not aspirin, on platelet aggregation.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking cocoa with antihypertensive drugs might increase the risk of hypotension.
Clinical research shows that cocoa can modestly decrease blood pressure in hypertensive and normotensive patients.

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

Theoretically, large amounts of cocoa might increase the cardiac inotropic effects of beta-agonists.
Cocoa contains caffeine. Theoretically, large amounts of caffeine might increase cardiac inotropic effects of beta-agonists. A case of atrial fibrillation associated with consumption of large quantities of chocolate in a patient with chronic albuterol inhalation abuse has also been reported.

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

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

Likelihood Possible Evidence D
Dipyridamole (Persantine)

Theoretically, cocoa might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Cocoa contains caffeine. Caffeine may 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 than adenosine-induced stress testing.

Likelihood Probable Evidence B
Disulfiram (Antabuse)

Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
Cocoa contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance.

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, using cocoa with diuretic drugs might increase the risk of hypokalemia.
Cocoa 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
Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Cocoa 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 Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Flutamide (Eulexin)

Theoretically, cocoa might increase the levels and adverse effects of flutamide.
Cocoa contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide.

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

Theoretically, abrupt cocoa withdrawal might increase the levels and adverse effects of lithium.
Cocoa contains caffeine. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal.

Likelihood Possible Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Cocoa contains caffeine. Large amounts of caffeine with MAOIs might precipitate a hypertensive crisis.

Likelihood Possible Evidence D
Nicotine

Theoretically, concomitant use might increase the risk of hypertension.
Cocoa contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly.

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

Theoretically, cocoa might decrease the effects of pentobarbital.
Cocoa contains caffeine. Caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

Theoretically, cocoa might reduce the effects of phenobarbital and increase the risk for convulsions.
Cocoa contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. The exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Phenylpropanolamine

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Cocoa contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure. Phenylpropanolamine also seems to increase caffeine serum levels.

Likelihood Probable Evidence B
Phenytoin (Dilantin)

Theoretically, cocoa might reduce the effects of phenytoin and increase the risk for convulsions.
Cocoa contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenytoin. The effect does not seem to be related to the seizure threshold-lowering effects of caffeine. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Cocoa contains caffeine. Quinolones (also referred to as fluoroquinolones) decrease caffeine clearance.

Likelihood Probable Evidence B
Riluzole (Rilutek)

Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Cocoa contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.
Cocoa contains caffeine. Concomitant use might increase the risk of stimulant adverse effects.

Likelihood Probable Evidence C
Theophylline

Theoretically, cocoa might increase the levels and adverse effects of theophylline.
Cocoa contains caffeine. Large amounts of caffeine might inhibit theophylline metabolism. Caffeine decreases theophylline clearance 23% to 29%.

Likelihood Probable Evidence B
Theobromine full monograph & all 37 interactions

L-Theanine3 drug types · 565 drugs

Antihypertensive Drugs

Theanine might lower blood pressure, potentiating the effects of antihypertensive drugs.
Animal research shows that theanine can lower blood pressure in spontaneously hypertensive animals. Theoretically, concomitant use of theanine and antihypertensive drugs might potentiate the antihypertensive activity.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, theanine might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Theoretically, theanine may compete with glutamate and/or increase plasma gamma-aminobutyric acid (GABA) levels, which could cause CNS depression. In one clinical study, some subjects taking oral theanine reported drowsiness.

Likelihood Unlikely Evidence D
Serotonergic Drugs

Clinical studies regarding the effects of L-theanine on serotonin levels are conflicting. Some studies suggest it can increase serotonin levels in the brain while others report that it may decrease them. Nevertheless, there have been no reports of l-theanine being a causative agent in serotonergic-related side effects or serotonin syndrome.

Likelihood Unlikely Evidence C
L-Theanine 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-Hydroxytryptophan3 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-Hydroxytryptophan full monograph & interactions

Rosemary Leaf Extract6 drug types · 372 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, rosemary may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that rosemary inhibits platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking rosemary with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research shows that rosemary extract can decrease blood glucose levels in diabetic models. However, research in humans is conflicting. Although rosemary powder decreased blood glucose levels in healthy adults, no change in blood glucose levels was seen in adults with type 2 diabetes, most of whom were taking antidiabetes drugs.

Likelihood Possible Evidence B
Aspirin

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as aspirin.
Rosemary is reported to contain salicylates.

Likelihood Possible Evidence D
Choline Magnesium Trisalicylate (Trilisate)

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as choline magnesium trisalicylate.
Rosemary is reported to contain salicylate.

Likelihood Possible Evidence D
Salsalate (Disalcid)

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as salsalate.
Rosemary is reported to contain salicylate.

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

Theoretically, rosemary might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that rosemary induces CYP1A2 enzymes. This effect has not been reported in humans.

Likelihood Unlikely Evidence D
Rosemary Leaf Extract full monograph & interactions

Lion's Mane Mushroom Extract3 drug types · 327 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, lion's mane mushroom may increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
In vitro research suggests that lion's mane mushroom extracts can inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, lion's mane mushroom may have additive effects when used with antidiabetes drugs.
Animal research suggests that an aqueous extract of lion's mane mushroom can reduce serum glucose and increase serum insulin.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, concurrent use of lion's mane mushroom might interfere with immunosuppressive therapy.
In animal and in vitro research, lion's mane mushroom polysaccharides stimulate the immune system.

Likelihood Possible Evidence D
Lion's Mane Mushroom Extract full monograph & interactions

Magnesium15 drug types · 295 drugs

Levodopa/Carbidopa (Sinemet)

Magnesium can reduce the bioavailability of levodopa/carbidopa.
Clinical research in healthy volunteers shows that taking magnesium oxide 1000 mg with levodopa 100 mg/carbidopa 10 mg reduces the area under the curve (AUC) of levodopa by 35% and of carbidopa by 81%. In vitro and animal research shows that magnesium produces an alkaline environment in the digestive tract, which might lead to degradation and reduced bioavailability of levodopa/carbidopa.

Likelihood Probable Evidence B
Aminoglycoside Antibiotics

Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
Both aminoglycosides and magnesium reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade and possible paralysis. This is most likely to occur with high doses of magnesium given intravenously.

Likelihood Possible Evidence D
Antacids

Use of acid reducers may reduce the laxative effect of magnesium oxide.
A retrospective analysis shows that, in the presence of H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs), a higher dose of magnesium oxide is needed for a laxative effect. This may also occur with antacids. Under acidic conditions, magnesium oxide is converted to magnesium chloride and then to magnesium bicarbonate, which has an osmotic laxative effect. By reducing acidity, antacids may reduce the conversion of magnesium oxide to the active bicarbonate salt.

Likelihood Possible Evidence D
Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Magnesium 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 magnesium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Magnesium can decrease absorption of bisphosphonates.
Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours.

Likelihood Probable Evidence B
Calcium Channel Blockers

Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.
Magnesium inhibits calcium entry into smooth muscle cells and may therefore have additive effects with calcium channel blockers. Severe hypotension and neuromuscular blockades may occur when nifedipine is used with intravenous magnesium, although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness. High doses of magnesium could theoretically have additive effects with other calcium channel blockers.

Likelihood Possible Evidence D
Digoxin

Magnesium salts may reduce absorption of digoxin.
Clinical evidence suggests that treatment with oral magnesium hydroxide or magnesium trisilicate reduces absorption of digoxin from the intestines. This may reduce the blood levels of digoxin and decrease its therapeutic effects.

Likelihood Possible Evidence B
Potassium-Sparing Diuretics

Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.
Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics. Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.

Likelihood Probable Evidence D
Quinolone Antibiotics

Magnesium decreases absorption of quinolones.
Magnesium can form insoluble complexes with quinolones and decrease their absorption. Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects and accelerating the onset of effect.
Parenteral magnesium shortens the time to onset of skeletal muscle relaxants by about 1 minute and prolongs the duration of action by about 2 minutes. Magnesium potentiates the effects of skeletal muscle relaxants by decreasing calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes. Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate. A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg. Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time. It does not affect the activity of subsequently administered neostigmine.

Likelihood Probable Evidence A
Sulfonylureas

Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.
Clinical research shows that administration of magnesium hydroxide with glyburide increases glyburide absorption, increases maximal insulin response by 35-fold, and increases the risk of hypoglycemia, when compared with glyburide alone. A similar interaction occurs between magnesium hydroxide and glipizide. The mechanism of this effect appears to be related to the elevation of gastrointestinal pH by magnesium-based antacids, increasing solubility and enhancing absorption of sulfonylureas.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Magnesium decreases absorption of tetracyclines.
Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity. Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.
In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations. Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity. However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur.

Likelihood Unlikely Evidence B
Gabapentin (Neurontin)

Gabapentin absorption can be decreased by magnesium.
Clinical research shows that giving magnesium oxide orally along with gabapentin decreases the maximum plasma concentration of gabapentin by 33%, time to maximum concentration by 36%, and area under the curve by 43%. Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Unlikely Evidence B
Sevelamer (Renagel, Renvela)

Sevelamer may increase serum magnesium levels.
In patients on hemodialysis, sevelamer use was associated with a 0.28 mg/dL increase in serum magnesium. The mechanism of this interaction remains unclear.

Likelihood Possible Evidence B
Magnesium full monograph & interactions

Kanna Leaf Extract1 drug type · 248 drugs

Cns Depressants

Theoretically, concomitant use of sceletium and CNS depressants might result in additive sedative effects.
Some evidence suggests that sceletium has sedative properties.

Likelihood Possible Evidence D
Kanna Leaf Extract full monograph & interactions

Theacrine1 drug type · 248 drugs

Cns Depressants

Theoretically, theacrine might alter the effects of CNS depressants.
Animal research shows that low doses of theacrine have sedating effects, whereas high doses might have stimulant effects. Depending on the dose of theacrine used, it might increase or decrease the effects of CNS depressants. However, these effects have not yet been reported in humans.

Likelihood Possible Evidence D
Theacrine full monograph & interactions

Phosphatidylserine2 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
Phosphatidylserine 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

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

Vitamin C13 drug types · 207 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Aluminum

Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption. In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely. Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

Likelihood Probable Evidence B
Antitumor Antibiotics

Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Estrogens

Vitamin C might increase blood levels of estrogens.
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements. Monitor these patients for estrogen-related side effects.

Likelihood Probable Evidence B
Fluphenazine (Prolixin)

Theoretically, vitamin C might decrease levels of fluphenazine.
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started. The mechanism is not known, and there is no further data to confirm this interaction.

Likelihood Possible Evidence D
Indinavir (Crixivan)

Vitamin C can modestly reduce indinavir levels.
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Vitamin C can increase levothyroxine absorption.
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH.

Likelihood Probable Evidence B
Warfarin (Coumadin)

High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption. There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time. Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant. However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

High-dose vitamin C might slightly prolong the clearance of acetaminophen.
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases. This effect is not likely to be clinically significant.

Likelihood Probable Evidence B
Aspirin

Acidification of the urine by vitamin C might increase aspirin levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction is not clinically significant.

Likelihood Possible Evidence B
Choline Magnesium Trisalicylate (Trilisate)

Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Niacin

Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol 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 vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Salsalate (Disalcid)

Acidification of the urine by vitamin C might increase salsalate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Vitamin C full monograph & interactions

Sodium Nitrite7 drug types · 205 drugs

Antihypertensive Drugs

Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.
High intake of dietary sodium can increase systolic and diastolic blood pressure. Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease.

Likelihood Probable Evidence A
Corticosteroids

Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.
Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone.

Likelihood Possible Evidence D
Didanosine (Videx)

Concomitant use of didanosine with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia.
Didanosine formulations contain a significant amount of sodium.

Likelihood Probable Evidence C
Lithium

Altering dietary intake of sodium might alter the levels and clinical effects of lithium.
High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion. Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate. Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L. Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

Likelihood Probable Evidence B
Sodium Phosphates

Theoretically, concomitant use of sodium phosphate with sodium supplements might increase the risk of hypernatremia.
Use of high doses (> 45 mL in 24 hours) of sodium phosphate, such as those used for bowel cleansing before surgery, can lead to serious electrolyte disturbances, including hypernatremia. The risk of hypernatremia is highest in the elderly and people with other risk factors for electrolyte disturbances.

Likelihood Possible Evidence D
Sodium-Containing Drugs

Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.
The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population. Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

Likelihood Possible Evidence D
Tolvaptan (Samsca)

Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.
Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia. Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

Likelihood Probable Evidence C
Sodium Nitrite full monograph & interactions

Acetyl L-Carnitine Arginate DiHCl4 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 Arginate DiHCl full monograph & interactions

Coenzyme Q-103 drug types · 198 drugs

Alkylating Agents

Coenzyme Q10 has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals.
Theoretically, antioxidants such as coenzyme Q10 might protect tumor cells from chemotherapeutic agents that work by inducing oxidative stress, such as alkylating agents (e.g., cyclophosphamide) and radiation therapy. The clinical importance of this interaction is unknown.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Coenzyme Q10 is chemically similar to menaquinone and might have vitamin K-like procoagulant effects, which could decrease the effects of warfarin.
Concomitant use of coenzyme Q10 and warfarin might reduce the anticoagulant effects of warfarin. Four cases of decreased warfarin efficacy thought to be due to coenzyme Q10 have been reported. However, there is some preliminary clinical research that suggests coenzyme Q10 might not significantly decrease the effects of warfarin in patients who have a stable INR.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, coenzyme Q10 might have additive effects with antihypertensive drugs.
Some clinical research shows that coenzyme Q10 can significantly lower blood pressure, although other studies have shown conflicting results.

Likelihood Possible Evidence B
Coenzyme Q-10 full monograph & interactions

Phenylethylamine2 drug types · 187 drugs

Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking phenethylamine concomitantly with MAOIs may increase adverse effects.
In humans, phenethylamine is oxidized by MAO-B to form the inactive metabolite phenylacetic acid. Animal research shows that administering an MAOI prior to phenethylamine increases the amphetamine-like effects of phenethylamine. However, low-quality clinical research has used phenethylamine with selegiline, an MAOI, with apparent safety.

Likelihood Possible Evidence D
Serotonergic Drugs

Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of serotonergic adverse effects.
Animal research shows that phenethylamine increases levels of serotonin, norepinephrine, and dopamine. Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of additive serotonergic adverse effects, including serotonin syndrome and cerebral vasoconstrictive disorders. However, low-quality clinical research has used phenethylamine with selegiline, a monoamine oxidase inhibitor (MAOI), with apparent safety.

Likelihood Possible Evidence D
Phenylethylamine full monograph & interactions

Shilajit extract1 drug type · 86 drugs

Antidiabetes Drugs

Taking shilajit with antidiabetes drugs might increase the risk of hypoglycemia.
Most human and animal research shows that shilajit can decrease fasting plasma glucose levels. In an animal model, shilajit 100 mg per kg daily enhanced the glucose-lowering ability of both glibenclamide and metformin when given in combination over a 4 week period. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Likelihood Possible Evidence D
Shilajit extract full monograph & interactions

Pregnenolone5 drug types · 82 drugs

Benzodiazepines

Concomitant use of pregnenolone may reduce the effects of benzodiazepines.
Very preliminary clinical research shows that chronic use of pregnenolone reduces sedative effects of diazepam when compared with chronic use of placebo. This effect may be related to the activity of pregnenolone at GABAA receptors.

Likelihood Probable Evidence B
Estrogens

Theoretically, taking pregnenolone might enhance the effects of estrogens.
Pregnenolone is a precursor for several steroid hormones, including estrogens.

Likelihood Possible Evidence D
Progesterone

Theoretically, taking pregnenolone might enhance the effects of progesterone.
In humans, some research shows that oral administration of pregnenolone can increase levels of progesterone. However, other research shows no effect on progesterone levels. It is possible the impact of pregnenolone on progesterone levels may be dose dependent.

Likelihood Possible Evidence D
Progestin

Theoretically, taking pregnenolone might enhance the effects of progestin.
Pregnenolone is a precursor for several steroid hormones, including progestin.

Likelihood Possible Evidence D
Testosterone

Theoretically, taking pregnenolone might enhance the effects of testosterone.
Pregnenolone is a precursor for several steroid hormones, including testosterone. However, preliminary clinical research shows that taking pregnenolone 30-500 mg orally daily for up to 8 weeks does not affect testosterone levels.

Likelihood Possible Evidence D
Pregnenolone 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

Pantael2 drug types · 52 drugs

Contraceptive Drugs

Theoretically, deer velvet might interfere with the effectiveness of contraceptive drugs.
Laboratory research shows that deer velvet contains small quantities of estradiol and testosterone. While clinical research shows that taking deer velvet extract does not raise testosterone levels, estradiol levels were not measured.

Likelihood Unlikely Evidence D
Estrogens

Theoretically, deer velvet might increase the effects and side effects of estrogens.
Laboratory evidence shows that deer velvet contains small quantities of estradiol and testosterone. While clinical research shows that taking deer velvet extract does not raise testosterone levels, estradiol levels were not measured.

Likelihood Unlikely Evidence D
Pantael 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

Vitamin B121 drug type · 20 drugs

Metformin (Glucophage)

Metformin, a common medication used to manage type 2 diabetes, has been associated with lower vitamin B12 levels in some individuals. Prolonged use of metformin can interfere with the absorption of B12 in the digestive system, potentially leading to a deficiency in this essential vitamin.

Likelihood Possible Evidence A
Vitamin B12 full monograph & interactions

Vitamin B21 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
Vitamin B2 full monograph & interactions

Alpha-Glycerylphosphorylcholine1 drug type · 16 drugs

Scopolamine (Transderm Scop)

Theoretically, alpha-GPC might decrease the effects of scopolamine.
A small clinical study shows that alpha-GPC can partially counteract the attention and memory impairment effects caused by scopolamine given intramuscularly. Whether alpha-GPC can decrease the beneficial anti-motion sickness effects of the scopolamine patch (Transderm Scop) is unclear.

Likelihood Possible Evidence B
Alpha-Glycerylphosphorylcholine full monograph & interactions

Iodine3 drug types · 7 drugs

Amiodarone (Cordarone)

Combining iodine with amiodarone might cause excessively high iodine levels.
Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use with iodine might increase the risk of having excessive iodine levels and adversely affecting thyroid function. Monitor thyroid function.

Likelihood Probable Evidence D
Antithyroid Drugs

Iodine might alter the effects of antithyroid drugs.
Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking iodine while using antithyroid drugs could alter the effects of the antithyroid drugs.

Likelihood Probable Evidence D
Lithium

Combining iodine with lithium might have additive hypothyroid effects.
Lithium can inhibit thyroid function. Several case reports suggest that concomitant use of lithium and potassium iodide can reduce thyroid function in otherwise healthy adults. Monitor thyroid function.

Likelihood Probable Evidence D
Iodine full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Limitless Mind, from the product label.

Lean Factor

See all Lean Factor products
Name
Lean Factor
Street Address
5407 N Haverhill Rd #337
City
West Palm Beach
State
FL
ZipCode
33407
Phone Number
800-818-7115
Web Address
www.LeanFactor.com
Pharmacist Counseling Corner

Limitless Mind by Lean Factor: Common Questions

Does Limitless Mind by Lean Factor interact with any medications?
Yes. Based on its ingredients, Limitless Mind has a known interaction with 1,926 medications, including 295 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Limitless Mind contains 65 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.
Can I take this while I'm pregnant?
Pregnancy safety varies by ingredient. Some vitamins like B12 and riboflavin are needed in pregnancy, while others (5-HTP, L-theanine, pregnenolone) lack safety data and should be avoided. Niacin, vitamin C, and L-tyrosine have cautions at high doses. Talk with your doctor before taking this product during pregnancy—they can advise based on your specific needs and dosages.
Is this safe to take while breastfeeding?
Some ingredients like methylcobalamin and riboflavin are safe at recommended amounts while breastfeeding. Others—5-HTP, L-theanine, and pregnenolone—lack sufficient safety data and are best avoided. Theobromine (cocoa) passes into breast milk and may make your baby fussy if taken in large amounts. Check with your doctor or pharmacist about whether this product is right for you while nursing.
What does L-theanine do in this product?
L-theanine is an amino acid from tea that may support calm focus and cognitive function. The evidence in our data shows it's possibly effective for cognitive function, but ratings for anxiety and other conditions lack reliable evidence. Common side effects are mild and include headache and drowsiness.
Will this help with focus and memory?
The product includes L-tyrosine (possibly effective for memory and cognition) and L-theanine (possibly effective for cognitive function), along with adaptogens like ashwagandha and rhodiola. However, effectiveness ratings for adaptogens and several other ingredients in our data show insufficient evidence or no established rating for focus or memory claims. Results vary by person; talk with your doctor about whether it's appropriate for your goals.
What are the most common side effects?
Common side effects depend on dose and individual tolerance. Niacin often causes flushing and may upset the stomach. 5-HTP can cause nausea, diarrhea, and drowsiness. Vitamin C at high doses may cause stomach cramps or loose stools. Zinc can cause nausea and a metallic taste. Theobromine (cocoa) adds caffeine and may cause headache or jitteriness. Start with the lowest dose and increase slowly if you experience side effects.
Why does the product have so many ingredients?
The formula combines B vitamins and minerals for foundational nutrition, herbal adaptogens (ashwagandha, rhodiola, eleuthero) to support stress resilience, amino acids and related compounds (L-tyrosine, 5-HTP, L-theanine) for cognition and mood, and pregnenolone as a hormone precursor. This 'stack' approach aims to address multiple pathways related to mental performance, though you should verify that all these ingredients are appropriate for your health situation before taking it.

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

Not sure if Limitless Mind 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.

Limitless Mind label
Go deeper

The Full Monographs Behind Limitless Mind’s Ingredients

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

Herb & supplement monograph

Ashwagandha

Interacts with 1,372 drugs

Ashwagandha is an Ayurvedic herb most often taken to help with stress, anxiety, and sleep, and some small studies suggest it may help, though the evidence is still limited. It is generally w...

Read the full Ashwagandha 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

Rhodiola

Interacts with 1,271 drugs

Rhodiola is an herb traditionally used to fight fatigue and help the body cope with stress. Some small studies suggest it may modestly reduce fatigue and improve mood, but the evidence is li...

Read the full Rhodiola monograph → Herb & supplement monograph

Shilajit

Interacts with 86 drugs

Shilajit is a sticky, tar-like substance found in rocks of mountain ranges like the Himalayas, used in traditional Ayurvedic medicine for energy and vitality. Human evidence is limited and m...

Read the full Shilajit 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

Deer Velvet

Interacts with 52 drugs

Deer velvet is a traditional remedy made from the soft, growing antlers of deer or elk, and it is most often promoted for energy, athletic performance, and joint health. Good-quality human e...

Read the full Deer Velvet monograph → Herb & supplement monograph

Silicon

Silicon is a trace mineral found in the body and in foods like oats, barley, and certain fruits and vegetables, and it is popular in supplements for hair, skin, nail, and bone health. Some s...

Read the full Silicon monograph → Herb & supplement monograph

Vitamin D

Interacts with 715 drugs

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people, especially those with low sun exposure,...

Read the full Vitamin D 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

Vitamin C

Interacts with 207 drugs

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for immune function, collagen, and acts as an...

Read the full Vitamin C monograph → Herb & supplement monograph

Sodium

Interacts with 205 drugs

Sodium is an essential mineral and electrolyte your body needs to balance fluids, support nerves, and help muscles work. Most people in modern diets get more than enough—often too much—from...

Read the full Sodium monograph → Herb & supplement monograph

Magnesium

Interacts with 295 drugs

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preventing or correcting deficiency. Some othe...

Read the full Magnesium monograph → Herb & supplement monograph

Coleus

Interacts with 915 drugs

Coleus is a plant from the mint family whose root contains a compound called forskolin, often marketed for weight loss, asthma, and heart health. While early lab and small human studies are...

Read the full Coleus 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

Vitamin B12

Interacts with 20 drugs

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very helpful for people who are deficient — su...

Read the full Vitamin B12 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

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

Iodine

Interacts with 7 drugs

Iodine is an essential mineral your body needs to make thyroid hormones, and most people get enough from iodized salt, dairy, and seafood. Supplements help when you are truly deficient, but...

Read the full Iodine 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

Theanine

Interacts with 565 drugs

Theanine (usually L-theanine) is an amino acid found naturally in tea leaves that many people take to feel calmer and less stressed without strong drowsiness. Early research suggests it may...

Read the full Theanine 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

Cocoa

Interacts with 661 drugs

Cocoa is rich in plant compounds called flavanols that may modestly support blood vessel function and blood pressure, but most chocolate products are high in sugar, fat, and calories, which...

Read the full Cocoa 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

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

Phenethylamine (pea)

Interacts with 187 drugs

Phenethylamine (PEA) is a natural compound made in the body and found in foods like chocolate; supplements are marketed for mood, focus, and energy. Reliable human research on the supplement...

Read the full Phenethylamine (pea) monograph → Herb & supplement monograph

Pregnenolone

Interacts with 82 drugs

Pregnenolone is a hormone your body makes naturally and a building block for other hormones like cortisol, DHEA, estrogen, and testosterone. It is sold as a supplement for memory, mood, and...

Read the full Pregnenolone monograph → Herb & supplement monograph

Rosemary

Interacts with 372 drugs

Rosemary is a fragrant Mediterranean herb that is safe and flavorful in normal food amounts. Some early research suggests possible benefits for memory, mood, and hair growth, but the evidenc...

Read the full Rosemary monograph → Herb & supplement monograph

Lion's Mane Mushroom

Interacts with 327 drugs

Lion's mane is an edible mushroom that is popular as a 'nootropic' for memory, focus, and nerve health, but solid human evidence is still limited and early. It is generally well tolerated as...

Read the full Lion's Mane Mushroom 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

Coenzyme Q10

Interacts with 198 drugs

CoQ10 is a vitamin-like substance your body makes naturally that helps cells produce energy and acts as an antioxidant. It is generally well tolerated and is most studied for heart condition...

Read the full Coenzyme Q10 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

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

Sceletium

Interacts with 248 drugs

Sceletium (often sold as 'kanna') is a South African plant traditionally used to ease stress and lift mood. Early human studies are small and short, so its benefits are not well proven. Talk...

Read the full Sceletium monograph → Herb & supplement monograph

Theacrine

Interacts with 248 drugs

Theacrine is a caffeine-like compound found naturally in certain tea plants and is sold in supplements for energy, focus, and mood. Early human studies suggest it may give a stimulant-like b...

Read the full Theacrine 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

Ergothioneine

Ergothioneine is a naturally occurring amino acid–like compound (an antioxidant) found mostly in mushrooms and made by certain fungi and bacteria. Early laboratory studies suggest it may hel...

Read the full Ergothioneine monograph → Herb & supplement monograph

Citicoline

Citicoline is a naturally occurring compound involved in making brain cell membranes and the messenger chemical acetylcholine. It is popularly taken for memory, focus, and brain aging, and s...

Read the full Citicoline monograph → Herb & supplement monograph

Ecklonia Cava

Ecklonia cava is an edible brown seaweed rich in plant compounds called phlorotannins that are studied as antioxidants. Early human and lab research hints at possible benefits for blood vess...

Read the full Ecklonia Cava 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

Turmeric

Interacts with 1,133 drugs

Turmeric is a popular spice whose main active compounds, curcuminoids, are studied mostly for inflammation and joint pain. Some research is promising, but quality is mixed and curcumin is po...

Read the full Turmeric monograph → Herb & supplement monograph

Alpha-gpc

Interacts with 16 drugs

Alpha-GPC is a choline-containing compound used mainly for memory, brain health, and as a choline source. There is some evidence it may help cognition in people with dementia, but evidence i...

Read the full Alpha-gpc monograph →
Sources

Sources & How We Checked

Limitless Mind'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 1,161 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.

Vitamin B12 30 references
  1. 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
  2. Hartman TJ, Woodson K, Stolzenberg-Solomon R, et al. Association of the B-vitamins pyridoxal 5'-phosphate (B6), B12, and folate with lung cancer risk in older men. Am J Epidemiol 2001;153:688-94.. DOI
  3. 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..
  4. 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
  5. 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
  6. Geissbuhler, P., Mermillod, B., and Rapin, C. H. Elevated serum vitamin B12 levels associated with CRP as a predictive factor of mortality in palliative care cancer patients: a prospective study over five years. J.Pain Symptom.Manage. 2000;20(2):93-103. PubMed
  7. Salles, N., Herrmann, F., Sakbani, K., Rapin, C. H., and Sieber, C. High vitamin B12 level: a strong predictor of mortality in elderly inpatients. J Am Geriatr.Soc 2005;53(5):917-918.
  8. Looker, H. C., Fagot-Campagna, A., Gunter, E. W., Pfeiffer, C. M., Sievers, M. L., Bennett, P. H., Nelson, R. G., Hanson, R. L., and Knowler, W. C. Homocysteine and vitamin B(12) concentrations and mortality rates in type 2 diabetes. Diabetes Metab Res R
  9. Uhl, W., Nolting, A., Golor, G., Rost, K. L., and Kovar, A. Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study. Clin Toxicol (Phila) 2006;44 Suppl 1:17-28. PubMed
  10. Borron, S. W., Baud, F. J., Barriot, P., Imbert, M., and Bismuth, C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg.Med 2007;49(6):794-801, 801. PubMed
  11. Borron, S. W., Baud, F. J., Megarbane, B., and Bismuth, C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg.Med 2007;25(5):551-558. PubMed
  12. Lewis, J. G. Gout, Steatorrhoea, and Megaloblastic Anaemia. Ann Rheum.Dis 1962;21(3):284-286. PubMed
  13. Tal, S., Shavit, Y., Stern, F., and Malnick, S. Association between vitamin B12 levels and mortality in hospitalized older adults. J Am Geriatr.Soc 2010;58(3):523-526. PubMed
  14. Baztan, J. J., Gavidia, J. J., Gomez-Pavon, J., Esteve, A., and Ruiperez, I. High vitamin B12 levels and in-hospital mortality. J Am Geriatr.Soc 2010;58(11):2237-2238. PubMed
  15. Omboni, E., Checchini, M., and Longoni, F. [Hypopotassemia and megaloblastic anemia. Presentation of a case]. Minerva Med 8-31-1987;78(16):1255-1257.
  16. Aalfs As, Scholvinck LH, Horvath B. Acneiform eruption in a 5-year old due to vitamin B12 supplementation. Eur J Dermatol 2013;23(5):726-7. PubMed
  17. Balta I, Ozuguz P. Vitamin B12-induced acneiform eruption. Cutan Ocul Toxicol 2014;33(2):94-5. PubMed
  18. Carman KB, Belgemen T, Yis U. Involuntary movements misdiagnosed as seizure during vitamin B12 treatment. Pediatr Emerg Care 2013;29(11):1223-4. PubMed
  19. Djuric V, Bogic M, Popadic AP, et al. Anaphylactic reaction to hydroxycobalamin with tolerance to cyanocobalamin. Ann Allergy Asthma Immunol 2012;108(3):207-8. PubMed
  20. Kartel O, Gulec M, Demirel F, et al. Vitamin B12 allergy and successful desensitization with cyanocobalamin: A case report. Allergol Immunopath (Madr) 2012;40(5):324-5.
  21. Patiroglu T, Unal E, Yildirim S. Infantile tremor syndrome associated with cobalamin therapy: A case report. Clin Neurol Neurosurg 2013;115(9):1903-5. PubMed
  22. Schulte S, Barkema LW, Kardaun SH. Long-lasting atypical acneiform eruption with prominent comedones induced by hydroxocobalamin (vitamin B12). J Dtsch Dermatol Ges 2014;12(6):502-3.
  23. Zanus C, Alberini E, Costa P, et al. Involuntary movements after correction of vitamin B12 deficiency: A video-case report. Epileptic Disord 2012;14(2):174-80. PubMed
  24. 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
  25. Fujita Y, Mizukami T, Maya Y, et al. Vitamin B12 allergy manifesting as lymphomatoid contact dermatitis. Eur J Dermatol. 2020;30(3):304-305. PubMed
  26. Dépret F, Hoffmann C, Daoud L, et al. Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study. Crit Care. 2019;23(1):421. PubMed
  27. Khairan P, Sobue T, Eshak ES, et al. Association of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer: the Japan Public Health Center-based (JPHC) prospective study. BMC Cancer 2021;21(1):982. PubMed
  28. Evans J, Pandya A, Ding Y, Qunibi WY. Hydroxocobalamin-Induced Oxalate Nephropathy in a Patient With Smoke Inhalation. Kidney Int Rep 2021;6(8):2228-2231. PubMed
  29. Lacombe V, Chabrun F, Lacout C, et al. Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer. Sci Rep 2021;11(1):13361. PubMed
  30. Pegalajar-García MD, Cebolla-Verdugo M, Prados-Carmona Á, Llamas-Segura C, Navarro-Triviño FJ. Systemic allergic dermatitis to cobalt present in cyanocobalamin supplementation. Contact Dermatitis 2023;89(3):203-205. PubMed

See these in context on the Vitamin B12 monograph →

Silicon 19 references
  1. 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.
  2. Jugdaohsingh R, Anderson SH, Tucker KL, et al. Dietary silicon intake and absorption. Am J Clin Nutr 2002;75:887-93. PubMed
  3. Ichiyanagi O, Sasagawa I, Adachi Y, et al. Silica urolithiasis without magnesium trisilicate intake. Urol Int 1998;61:39-42. PubMed
  4. Levison DA, Crocker PR, Banim S, Wallace DM. Silica stones in the urinary bladder. Lancet 1982;1:704-5. PubMed
  5. Lee MH, Lee YH, Hsu TH, et al. Silica stone--development due to long time oral trisilicate intake. Scand J Urol Nephrol 1993;27:267-9. PubMed
  6. Cruz Guerra, N. A., Gomez Garcia, M. A., Lovaco, Castellano F., Saez Garrido, J. C., Garcia, Cuerpo E., and Escudero, Barrilero A. [Silica urolithiasis: report of a new case]. Actas Urol.Esp 2000;24(2):202-204.
  7. Merget, R., Bauer, T., Kupper, H. U., Philippou, S., Bauer, H. D., Breitstadt, R., and Bruening, T. Health hazards due to the inhalation of amorphous silica. Arch Toxicol. 2002;75(11-12):625-634. PubMed
  8. Khuder, S. A., Peshimam, A. Z., and Agraharam, S. Environmental risk factors for rheumatoid arthritis. Rev Environ Health 2002;17(4):307-315. PubMed
  9. McLaughlin, J. K., Chow, W. H., and Levy, L. S. Amorphous silica: a review of health effects from inhalation exposure with particular reference to cancer. J Toxicol.Environ Health 4-25-1997;50(6):553-566. DOI
  10. Pelucchi, C., Pira, E., Piolatto, G., Coggiola, M., Carta, P., and La, Vecchia C. Occupational silica exposure and lung cancer risk: a review of epidemiological studies 1996-2005. Ann.Oncol. 2006;17(7):1039-1050. PubMed
  11. Gillissen, A., Gessner, C., Hammerschmidt, S., Hoheisel, G., and Wirtz, H. [Health significance of inhaled particles]. Dtsch.Med Wochenschr. 3-24-2006;131(12):639-644.
  12. Hu, J. F., Qu, H., and Wang, J. Z. [Meta analysis for relationship between exposure of free silicon dioxide and lung tumor]. Zhonghua Lao.Dong.Wei Sheng Zhi.Ye.Bing.Za Zhi. 2006;24(7):415-417.
  13. Jugdaohsingh, R. Silicon and bone health. J Nutr Health Aging 2007;11(2):99-110.
  14. Lacasse, Y., Martin, S., Gagne, D., and Lakhal, L. Dose-response meta-analysis of silica and lung cancer. Cancer Causes Control 2009;20(6):925-933. PubMed
  15. McCormic, Z. D., Khuder, S. S., Aryal, B. K., Ames, A. L., and Khuder, S. A. Occupational silica exposure as a risk factor for scleroderma: a meta-analysis. Int Arch Occup.Environ Health 2010;83(7):763-769. PubMed
  16. Haddad, F. S. and Kouyoumdjian, A. Silica stones in humans. Urol.Int 1986;41(1):70-76. PubMed
  17. Tervaert, J. W., Stegeman, C. A., and Kallenberg, C. G. Silicon exposure and vasculitis. Curr Opin.Rheumatol 1998;10(1):12-17. PubMed
  18. Steenland, K. and Stayner, L. Silica, asbestos, man-made mineral fibers, and cancer. Cancer Causes Control 1997;8(3):491-503. PubMed
  19. Boqué N, Valls RM, Pedret A, Puiggrós F, Arola L, Solà R. Relative absorption of silicon from different formulations of dietary supplements: a pilot randomized, double-blind, crossover post-prandial study. Sci Rep 2021;11(1):16479. PubMed

See these in context on the Silicon monograph →

Vitamin D 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  3. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-7. PubMed
  4. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  5. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialyzed patients taking AI(OH)3. Clin Nephrol 1986;26:146-9.
  6. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  7. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  8. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  9. Moon J. The role of vitamin D in toxic metal absorption. J Am Coll Nutr 1994;13:559-64.
  10. Demontis R, Reissi D, Noel C, et al. Indirect clinical evidence that 1alphaOH vitamin D<SUB>3</SUB> increases the intestinal absorption of aluminum. Clin Nephrol 1989;31:123-7.
  11. Adler AJ, Berlyne GM. Duodenal aluminum absorption in the rat: effect of vitamin D. Am J Physiol 1985;249:G209-13. PubMed
  12. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  13. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  14. Cox KA, Dunn MA. Aluminum toxicity alters the regulation of calbindin-D28k protein and mRNA expression in chick intestine. J Nutr 2001;131:2007-13. PubMed
  15. Escribano, J., Balaguer, A., Pagone, F., Feliu, A., and Roque, I. Figuls. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane.Database.Syst.Rev. 2009;(1):CD004754. PubMed
  16. Carlton, S., Clopton, D., and Cappuzzo, K. A. Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. Consult Pharm 2010;25(3):171-177. PubMed
  17. Wang, H., Xia, N., Yang, Y., and Peng, D. Q. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis. 2012;11:42. PubMed
  18. Turner AN, Carr Reese P, Fields KS, Anderson J, Ervin M, Davis JA, Fichorova RN, Roberts MW, Klebanoff MA, Jackson RD. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis. Am J Obstet G PubMed
  19. Weiner M, Epstein FH. Signs and symptoms of electrolyte disorders. Yale J Biol Med. 1970;43(2):76-109.
  20. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  21. Roth DE, Leung M, Mesfin E, Qamar H, Watterworth J, Papp E. Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ. 2017;359:j5237. PubMed
  22. Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: A randomized clinical trial. JAMA. 2021.
  23. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54-8. PubMed
  24. Doyle D, Browne U, Brickley A, Murphy D. Vitamin D-induced hypercalcaemia and acute kidney injury in sarcoidosis. BMJ Case Rep 2023;16(1):e250580. PubMed
  25. Williamson A, Martineau AR, Sheikh A, Jolliffe D, Griffiths CJ. Vitamin D for the management of asthma. Cochrane Database Syst Rev 2023;2(2):CD011511. PubMed
  26. Kinesya E, Santoso D, Gde Arya N, et al. Vitamin D as adjuvant therapy for diabetic foot ulcers: Systematic review and meta-analysis approach. Clin Nutr ESPEN 2023;54:137-143. PubMed

See these in context on the Vitamin D 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 →

Vitamin C 51 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
  3. Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
  4. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  5. Dwyer JH, Merz NB, Shirocre AM, et al. Progression of early atherosclerosis and intake of vitamin C and vitamin E from supplements and food. The Los Angeles Atherosclerosis Study. 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevent
  6. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. PubMed
  7. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  8. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  9. 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/.
  10. Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21. PubMed
  11. 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
  12. Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671. DOI
  13. Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479. DOI
  14. Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166. DOI
  15. Traxer O, Huet B, Poindexter J, et al. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003;170:397-401.. PubMed
  16. Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.
  17. Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601. PubMed
  18. Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7. PubMed
  19. Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413. DOI
  20. Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31. PubMed
  21. Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008. DOI
  22. Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35. PubMed
  23. Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70. PubMed
  24. 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
  25. Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7. PubMed
  26. Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6. PubMed
  27. Lee DH, Folsom AR, Harnack L, et al. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr 2004;80:1194-200. PubMed
  28. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15:3225-32. PubMed
  29. 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
  30. 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
  31. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  32. Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.
  33. Gruenwald, J., Graubaum, H. J., Busch, R., and Bentley, C. Safety and tolerance of ester-C compared with regular ascorbic acid. Adv.Ther. 2006;23(1):171-178.
  34. 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
  35. Einerson, B., Nathorn, C., Kitiyakara, C., Sirada, M., and Thamlikitkul, V. The efficacy of ascorbic acid in suboptimal responsive anemic hemodialysis patients receiving erythropoietin: a meta-analysis. J Med.Assoc.Thai. 2011;94 Suppl 1:S134-S146.
  36. Li, G., Li, L., Yu, C., and Chen, L. Effect of vitamins C and E supplementation on Helicobacter pylori eradication: a meta-analysis. Br.J Nutr 2011;106(11):1632-1637.
  37. Chen X, Shen L, Gu X, et al. High-dose supplementation with vitamin C--induced pediatric urolithiasis: the first case report in a child and literature review. Urology. 2014;84(4):922-4. PubMed
  38. Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6. PubMed
  39. Yaich S, Chaabouni Y, Charfeddine K, et al. Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014;25(1):113-6. PubMed
  40. 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
  41. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004072. PubMed
  42. Seo MS, Kim JK, Shim JY. High-dose vitamin C promotes regression of multiple pulmonary metastases originating from hepatocellular carcinoma. Yonsei Med J. 2015;56(5):1449-52. PubMed
  43. Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403. PubMed
  44. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic acid supplements and kidney stones incidence among men and women: a systematic review and meta-analysis. Urol J. 2019;16(2):115-120.
  45. Thomas S, Patel D, Bittel B, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2 PubMed
  46. Giffen MA, McLemore JL. Hyperoxalosis Secondary to Intravenous Vitamin C Administration as a Non-Allopathic Treatment for Cancer. Acad Forensic Pathol 2019;9(1-2):118-126. PubMed
  47. Maike A, Sturgill D, Gallan A. Oxalate Nephropathy in a Renal Transplant Recipient After Receiving High Dose Ascorbic Acid. Am J Med Sci 2021. PubMed
  48. Shen ZY, Chen YR, Wang MC, Chang SS. High-dose vitamin C-induced acute oxalate nephropathy in a renal transplant recipient: a case report and literature review. Asian J Surg 2022. PubMed
  49. Yanase F, Spano S, Maeda A, et al. Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial. Crit Care 2023;27(1):371. PubMed
  50. Sharma Y, Sumanadasa S, Shahi R, et al. Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis. Sci Rep 2024;14(1):11846. PubMed
  51. Pejcic AV, Petrovic NZ, Djordjic MD, Milosavljevic MN. Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis. Balkan Med J 2024;41(4):248-260. PubMed

See these in context on the Vitamin C 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 →

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 →

Iodine 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Goodman GA, Rall TW, Nies AS, Taylor P. The Pharmacological Basis of Therapeutics, 9th ed.
  3. Ghent WR, Eskin BA, Low DA, Hill LP. Iodine replacement in fibrocystic disease of the breast. Can J Surg 1993;36:453-60.
  4. Potassium iodide for nuclear exposure. Pharmacist's Letter/Prescriber's Letter 2001;17(12):171214.
  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. Cabezas C, Bustamante B, Holgado W, Begue RE. Treatment of cutaneous sporotrichosis with one daily dose of potassium iodide. Pediatr Infect Dis J 1996;15:352-4. PubMed
  7. Sterling JB, Heymann WR. Potassium iodide in dermatology: a 19th century drug for the 21st century-uses, pharmacology, adverse effects, and contraindications. J Am Acad Dermatol 2000;43:691-7. PubMed
  8. Yarrington CD, Pearce EN. Dietary iodine in pregnancy and postpartum. Clin Obstet Gynecol 2011;54:459-70. PubMed
  9. Goel, S., Mandhani, A., Srivastava, A., Kapoor, R., Gogoi, S., Kumar, A., and Bhandari, M. Is povidone iodine an alternative to silver nitrate for renal pelvic instillation sclerotherapy in chyluria? BJU.Int 2004;94(7):1082-1085. PubMed
  10. Teng, W., Shan, Z., Teng, X., Guan, H., Li, Y., Teng, D., Jin, Y., Yu, X., Fan, C., Chong, W., Yang, F., Dai, H., Yu, Y., Li, J., Chen, Y., Zhao, D., Shi, X., Hu, F., Mao, J., Gu, X., Yang, R., Tong, Y., Wang, W., Gao, T., and Li, C. Effect of iodine int
  11. Crawford, B. A., Cowell, C. T., Emder, P. J., Learoyd, D. L., Chua, E. L., Sinn, J., and Jack, M. M. Iodine toxicity from soy milk and seaweed ingestion is associated with serious thyroid dysfunction. Med J Aust. 10-4-2010;193(7):413-415. PubMed
  12. Ohkuma, M. Molluscum contagiosum treated with iodine solution and salicylic acid plaster. Int J Dermatol. 1990;29(6):443-445. PubMed
  13. Connelly KJ, Boston BA, Pearce EN, Sesser D, Snyder D, Braverman LE, Pino S, LaFranchi SH. Congenital hypothyroidism caused by excess prenatal maternal iodine ingestion. J Pediatr. 2012 Oct;161(4):760-2. PubMed
  14. Kasahara T, Narumi S, Okasora K, Takaya R, Tamai H, Hasegawa T. Delayed onset congenital hypothyroidism in a patient with DUOX2 mutations and maternal iodine excess. Am J Med Genet A. 2013 Jan;161A(1):214-7.
  15. Murcia M, Rebagliato M, Iñiguez C, Lopez-Espinosa MJ, Estarlich M, Plaza B, Barona-Vilar C, Espada M, Vioque J, Ballester F. Effect of iodine supplementation during pregnancy on infant neurodevelopment at 1 year of age. Am J Epidemiol. 2011 Apr 1;173(7):8 PubMed
  16. Sang Z, Wang PP, Yao Z, Shen J, Halfyard B, Tan L, Zhao N, Wu Y, Gao S, Tan J, Liu J, Chen Z, Zhang W. Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial. Am J Clin Nutr. 2012 Feb;95(2):367-73 PubMed
  17. Speeckaert MM, Speeckaert R, Wierckx K, Delanghe JR, Kaufman JM. Value and pitfalls in iodine fortification and supplementation in the 21st century. Br J Nutr. 2011 Oct;106(7):964-73. PubMed
  18. Yun SE, Kang Y, Bae EJ, Hwang K, Jang HN, Cho HS, Chang SH, Park DJ. Iodine-induced thyrotoxic hypokalemic paralysis after ingestion of Salicornia herbace. Ren Fail. 2014 Apr;36(3):461-3.
  19. Iodine Hypersensitivity. Pharmacist's Letter/Prescriber's Letter 2011; 27(5):270504.
  20. Hammel JA, Selby JC. Pustular eruption in a patient with cancer treated with complementary and alternative medicine. JAMA Dermatology 2017 October; E1. doi: 10.1001/jamadermatol.2017.3749. [Epub ahead of print] PubMed
  21. Gil GS, Smith BW, Guerra JR, Williams WT. Acute Delirium in a Hypothyroid Patient Precipitated by Iodine Supplements Use. Am J Ther. 2018;25(6):e717-e718. PubMed
  22. Hamby T, Kunnel N, Dallas JS, Wilson DP. Maternal iodine excess: an uncommon cause of acquired neonatal hypothyroidism. J Pediatr Endocrinol Metab. 2018;31(9):1061-1064. PubMed
  23. Censi S, Watutantrige-Fernando S, Groccia G, et al. The Effects of Iodine Supplementation in Pregnancy on Iodine Status, Thyroglobulin Levels and Thyroid Function Parameters: Results from a Randomized Controlled Clinical Trial in a Mild-to-Moderate Iodine
  24. Rovner MS, Wolf BJ, Rubin M, et al. Instillation of 5% Povidone-Iodine Ophthalmic Drops Decreases the Respiratory Rate in Children Undergoing Strabismus Surgery: A Randomized Controlled Trial. J Pediatr Ophthalmol Strabismus. 2019;56(6):378-382. PubMed
  25. Guenezan J, Garcia M, Strasters D, et al. Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2021;147(4):400-401. PubMed
  26. Li F, Wan S, Zhang L, et al. A Meta-Analysis of the Effect of Iodine Excess on the Intellectual Development of Children in Areas with High Iodine Levels in their Drinking Water. Biol Trace Elem Res 2022;200(4):1580-1590. PubMed

See these in context on the Iodine 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 →

Theanine 6 references
  1. Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-glutamylethylamide in spontaneously hypertensive rats. Life Sci 1998;62:1065-8.
  2. Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., and Scholey, A. B. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol.Psychol. 2008;77(2):113-122. PubMed
  3. Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T., and Takeuchi, N. Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci.Biotechnol.Biochem. 1995;59(4):615-618. PubMed
  4. Lyon MR, Kapoor MP, Juneja LR. The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern Med Rev. 2011;16(4):348-
  5. Hidese S, Ota M, Wakabayashi C, et al. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr 2017;29(2):72-9.
  6. Tsuchiya T, Honda H, Oikawa M, et al. Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients. Int J Clin Oncol 2016;21(6):1085-90. PubMed

See these in context on the Theanine 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 →

Cocoa 119 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  3. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  4. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
  5. 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
  6. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  7. 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
  8. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  9. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  10. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  11. 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.
  12. Baron AM, Donnerstein RL, Samson RA, et al. Hemodynamic and electrophysiologic effects of acute chocolate ingestion in young adults. Am J Cardiol 1999;84:370-3. PubMed
  13. Friedman G. Diet and the irritable bowel syndrome. Gastroenterol Clin North Am 1991;20:313-24. DOI
  14. 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.
  15. 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
  16. Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
  17. Weisburger JH. Tea and health: the underlying mechanisms. Proc Soc Exp Biol Med 1999;220:271-5. PubMed
  18. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  19. 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
  20. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  21. Dietrich R, Paglieroni TG, Wun T, et al. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000;72:30-5. PubMed
  22. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  23. 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
  24. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  25. 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
  26. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  27. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. PubMed
  28. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  29. 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
  30. 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
  31. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  32. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  33. 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
  34. 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.
  35. 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
  36. 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
  37. Vlachopoulos C, Aznaouridis K, Alexopoulos N, et al. Effect of dark chocolate on arterial function in healthy individuals. Am J Hypertens 2005;18:785-91.. PubMed
  38. Taubert D, Berkels R, Roesen R, Klaus W. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA 2003;290:1029-30.. PubMed
  39. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  40. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  41. Grassi D, Necozione S, Lippi C, et al. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 2005;46:398-405. PubMed
  42. Taubert D, Roesen R, Schomig E. Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med 2007;167:626-34. PubMed
  43. Taubert D, Roesen R, Lehmann C, et al. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA 2007;298:49-60. PubMed
  44. 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
  45. Flammer AJ, Hermann F, Sudano I, et al. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation 2007;116:2376-82. PubMed
  46. Hooper L, Kay C, Abdelhamid A, et al. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr 2012;95:740-51. PubMed
  47. Desideri G, Kwik-Uribe C, Grassi D, et al. Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: the Cocoa, Cognition, and Aging (CoCoA) study. Hyperte PubMed
  48. 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.
  49. 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
  50. 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
  51. 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.
  52. 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
  53. 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.
  54. 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
  55. 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
  56. 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.
  57. 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
  58. 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.
  59. Zubair, M. H., Zubair, M. H., Zubair, M. N., Zubair, M. M., Aftab, T., and Asad, F. Augmentation of anti-platelet effects of aspirin. J Pak Med.Assoc. 2011;61(3):304-307.
  60. Kot M, Daniel WA. Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep 2008;60:789-97.
  61. 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
  62. 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
  63. 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.
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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.
  69. 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.
  70. 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
  71. 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
  72. 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
  73. 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
  74. 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
  75. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  76. 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
  77. Lee, A. and Storey, D. M. Comparative gastrointestinal tolerance of sucrose, lactitol, or D-tagatose in chocolate. Regul.Toxicol.Pharmacol. 1999;29(2 Pt 2):S78-S82.
  78. Rein, D., Paglieroni, T. G., Wun, T., Pearson, D. A., Schmitz, H. H., Gosselin, R., and Keen, C. L. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000;72(1):30-35. PubMed
  79. Todd, S., Corsnitz, D., Ray, S., and Nassar, J. Outpatient laparoscopic Nissen fundoplication. AORN J 2002;75(5):956, 959-4. PubMed
  80. Pearson, D. A., Paglieroni, T. G., Rein, D., Wun, T., Schramm, D. D., Wang, J. F., Holt, R. R., Gosselin, R., Schmitz, H. H., and Keen, C. L. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb.Res 5-15-2002;106(4-5):191-1 PubMed
  81. Murphy, K. J., Chronopoulos, A. K., Singh, I., Francis, M. A., Moriarty, H., Pike, M. J., Turner, A. H., Mann, N. J., and Sinclair, A. J. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am J Clin Nutr 2 PubMed
  82. Innes, A. J., Kennedy, G., McLaren, M., Bancroft, A. J., and Belch, J. J. Dark chocolate inhibits platelet aggregation in healthy volunteers. Platelets. 2003;14(5):325-327. PubMed
  83. Castell, D. O., Murray, J. A., Tutuian, R., Orlando, R. C., and Arnold, R. Review article: the pathophysiology of gastro-oesophageal reflux disease - oesophageal manifestations. Aliment.Pharmacol.Ther. 2004;20 Suppl 9:14-25. PubMed
  84. Zumbe, A. and Brinkworth, R. A. Comparative studies of gastrointestinal tolerance and acceptability of milk chocolate containing either sucrose, isomalt or sorbitol in healthy consumers and type II diabetics. Z.Ernahrungswiss. 1992;31(1):40-48. PubMed
  85. Hermann, F., Spieker, L. E., Ruschitzka, F., Sudano, I., Hermann, M., Binggeli, C., Luscher, T. F., Riesen, W., Noll, G., and Corti, R. Dark chocolate improves endothelial and platelet function. Heart 2006;92(1):119-120.
  86. Kaltenbach, T., Crockett, S., and Gerson, L. B. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch.Intern.Med 5-8-2006;166(9):965-971. PubMed
  87. Heptinstall, S., May, J., Fox, S., Kwik-Uribe, C., and Zhao, L. Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc.Pharmacol. 2006;47 Suppl 2:S197-S205. PubMed
  88. Feldens, C. A., Vitolo, M. R., and Drachler, Mde L. A randomized trial of the effectiveness of home visits in preventing early childhood caries. Community Dent Oral Epidemiol 2007;35(3):215-223. PubMed
  89. Kannayiram, A., Rezaie, A., and Hadi, S. Chocolate-induced prolonged angiooedema in an elderly patient. Age Ageing 2008;37(4):479-480. PubMed
  90. Hooper, L., Kroon, P. A., Rimm, E. B., Cohn, J. S., Harvey, I., Le Cornu, K. A., Ryder, J. J., Hall, W. L., and Cassidy, A. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2008;88 PubMed
  91. Hamed, M. S., Gambert, S., Bliden, K. P., Bailon, O., Singla, A., Antonino, M. J., Hamed, F., Tantry, U. S., and Gurbel, P. A. Dark chocolate effect on platelet activity, C-reactive protein and lipid profile: a pilot study. South.Med J 2008;101(12):1203- PubMed
  92. Patane, S., Marte, F., La Rosa, F. C., and Rocca, R. L. Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse. Int J Cardiol. 1-24-2009; PubMed
  93. Ried, K., Frank, O. R., and Stocks, N. P. Dark chocolate or tomato extract for prehypertension: a randomised controlled trial. BMC.Complement Altern.Med. 2009;9:22. PubMed
  94. Desch, S., Schmidt, J., Kobler, D., Sonnabend, M., Eitel, I., Sareban, M., Rahimi, K., Schuler, G., and Thiele, H. Effect of cocoa products on blood pressure: systematic review and meta-analysis. Am J Hypertens. 2010;23(1):97-103. PubMed
  95. Davison, K., Berry, N. M., Misan, G., Coates, A. M., Buckley, J. D., and Howe, P. R. Dose-related effects of flavanol-rich cocoa on blood pressure. J Hum Hypertens. 2010;24(9):568-576. PubMed
  96. Desch, S., Kobler, D., Schmidt, J., Sonnabend, M., Adams, V., Sareban, M., Eitel, I., Bluher, M., Schuler, G., and Thiele, H. Low vs. higher-dose dark chocolate and blood pressure in cardiovascular high-risk patients. Am J Hypertens. 2010;23(6):694-700. PubMed
  97. Ried, K., Sullivan, T., Fakler, P., Frank, O. R., and Stocks, N. P. Does chocolate reduce blood pressure? A meta-analysis. BMC.Med 2010;8:39. PubMed
  98. van den Bogaard, B., Draijer, R., Westerhof, B. E., van den Meiracker, A. H., van Montfrans, G. A., and van den Born, B. J. Effects on Peripheral and Central Blood Pressure of Cocoa With Natural or High-Dose Theobromine. A Randomized, Double-Blind Crosso DOI
  99. Persson, I. A., Persson, K., Hagg, S., and Andersson, R. G. Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers--a nutrigenomics perspective. J Cardiovasc.Pharmac PubMed
  100. Khan, N., Monagas, M., Andres-Lacueva, C., Casas, R., Urpi-Sarda, M., Lamuela-Raventos, R. M., and Estruch, R. Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascu
  101. Listl, S. Family composition and children's dental health behavior: evidence from Germany. J Public Health Dent. 2011;71(2):91-101. PubMed
  102. Shrime, M. G., Bauer, S. R., McDonald, A. C., Chowdhury, N. H., Coltart, C. E., and Ding, E. L. Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies. J Nutr 2011;141(11):1982-1988. PubMed
  103. Sudarma, V., Sukmaniah, S., and Siregar, P. Effect of dark chocolate on nitric oxide serum levels and blood pressure in prehypertension subjects. Acta Med.Indones. 2011;43(4):224-228.
  104. Flammer, A. J., Sudano, I., Wolfrum, M., Thomas, R., Enseleit, F., Periat, D., Kaiser, P., Hirt, A., Hermann, M., Serafini, M., Leveques, A., Luscher, T. F., Ruschitzka, F., Noll, G., and Corti, R. Cardiovascular effects of flavanol-rich chocolate in pat
  105. Wolz, M., Schleiffer, C., Klingelhofer, L., Schneider, C., Proft, F., Schwanebeck, U., Reichmann, H., Riederer, P., and Storch, A. Comparison of chocolate to cacao-free white chocolate in Parkinson's disease: a single-dose, investigator-blinded, placebo-
  106. Ried, K., Sullivan, T. R., Fakler, P., Frank, O. R., and Stocks, N. P. Effect of cocoa on blood pressure. Cochrane.Database.Syst.Rev. 2012;8:CD008893. PubMed
  107. Rossner, S. Chocolate--divine food, fattening junk or nutritious supplementation? Eur.J Clin.Nutr. 1997;51(6):341-345. PubMed
  108. Storey, D. M., Koutsou, G. A., Lee, A., Zumbe, A., Olivier, P., Le Bot, Y., and Flourie, B. Tolerance and breath hydrogen excretion following ingestion of maltitol incorporated at two levels into milk chocolate consumed by healthy young adults with and w
  109. Izzo, A. A. and Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009;69(13):1777-1798. PubMed
  110. Ottaviani JI, Balz M, Kimball J, et al. Safety and efficacy of cocoa fl avanol intake in healthy adults: a randomized, controlled, double-masked trial. Am J Clin Nutr 2015;102(6):1425-35.
  111. 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
  112. United States Department of Agriculture Research Service. National Nutrient Database for Standard Reference. Basic Report: 19165, Cocoa, dry powder, unsweetened. https://ndb.nal.usda.gov/ndb/foods/show/19165. Updated April 2018. Accessed September 16, 20
  113. Jafarnejad S, Salek M, Clark CCT. Cocoa consumption and blood pressure in middle-aged and elderly subjects: a meta-analysis. Curr Hypertens Rep. 2020;22(1):1. PubMed
  114. Balayssac-Siransy E, Ouattara S, Boka KJM, et al. Dose-effect relation between regular consumption of 100% cocoa powder and blood pressure in young, healthy black Africans. Physiol Rep 2021;9(20):e15070. PubMed
  115. 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
  116. Devi P, Bajala V, Garg VK, Mor S, Ravindra K. Heavy metal content in various types of candies and their daily dietary intake by children. Environ Monit Assess. 2016;188(2):86. PubMed
  117. Abt E, Robin LP. Perspective on cadmium and lead in cocoa and chocolate. J Agric Food Chem. 2020;68(46):13008-13015. PubMed
  118. Consumer Reports. Lead and cadmium could be in your dark chocolate. December 2022. Available at: https://www.consumerreports.org/health/food-safety/lead-and-cadmium-in-dark-chocolate-a8480295550/. Accessed February 1, 2023.
  119. Seecheran NA, Sukha D, Grimaldos K, et al. Effect of cocoa (Theobroma cacao L.) on platelet function testing profiles in patients with coronary artery disease: ECLAIR pilot study. Open Heart 2022;9(2):e002066.

See these in context on the Cocoa 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 →

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 →

Phenethylamine (pea) 9 references
  1. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  2. Sabelli H, Fink P, Fawcett J, et al. Sustained antidepressant effect of PEA replacement. J Neuropsychiatry Clin Neurosci. 1996;8(2):168-71.
  3. Xie Z, Miller G. Beta-phenylehtylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. J Pharmacol Exp Ther. 2008;325(2):617-28.
  4. Lukasik-Glebocka M, Sommerfeld K, Tezyk A, et al. [Acute poisoning with weight-loss dietary supplement falsely suggesting the use of amphetamine]. Przegl Lek. 2013;70(10):880-3.
  5. Nakamura M, Ishii A, Nakahara D. Characterization of beta-phenyltheylamine-induced monoamine release in rat nucleus accumbens: a microdialysis study. Eur J Pharmacol. 1998;349(2-3):163-9.
  6. Bailey B, Philips S, Boulton A. In vivo release of endogenous dopamine, 5-hydroxytryptamine and some of their metabolites from rat caudate nucleus by phenylethylamine. Neurochem Res. 1987;12(2):173-8. PubMed
  7. Mantegazza P, Riva M. Amphetamine-like activity of beta-phenethylamine after a monoamine oxidase inhibitor in vivo. Journal of Pharmacy and Pharmacology. 1963;151(1):472-8.
  8. Grimsby J, Toth M, Chen K, et al. Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet. 1997;17(2):206-10.
  9. Lindemann L, Hoener MC. A renaissance in trace amines inspired by a novel GPCR family. Trends Pharmacol Sci. 2005;26(5):274-81. PubMed

See these in context on the Phenethylamine (pea) monograph →

Pregnenolone 6 references
  1. Devlin TM, ed. Textbook of Biochemistry With Clinical Correlations. third ed. New York: Wiley-Liss Inc., 1992.
  2. Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY.Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord 2014;44(11):2971-7. PubMed
  3. Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology 2014;39(12):2867-73. PubMed
  4. Ritsner MS, Gibel A, Shleifer T, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry 20 PubMed
  5. Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500. PubMed
  6. Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009;34(8):1885-903. PubMed

See these in context on the Pregnenolone monograph →

Ashwagandha 32 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. Upton R, ed. Ashwagandha Root (Withania somnifera): Analytical, quality control, and therapuetic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 2000:1-25.
  3. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett 2000;148:9-17. PubMed
  4. Davis L, Kuttan G. Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol 1998;62:209-14. PubMed
  5. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev 2000;5:334-46. DOI
  6. Andallu B, Radhika B. Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root. Indian J Exp Biol 2000;38:607-9.
  7. Kulkarni RR, Patki PS, Jog VP, et al. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 1991;33:91-5. PubMed
  8. Ahumada F, Aspee F, Wikman G, Hancke J. Withania somnifera exract. Its effects on arterial blood pressure in anaesthetized dogs. Phytother Res 1991;5:111-14.
  9. Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol 1999;67:233-39. PubMed
  10. Panda S, Kar A. Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice. J Pharm Pharmacol 1998;50:1065-68. PubMed
  11. Sehgal, V. N., Verma, P., and Bhattacharya, S. N. Fixed-drug eruption caused by ashwagandha (Withania somnifera): a widely used Ayurvedic drug. Skinmed. 2012;10(1):48-49.
  12. Agnihotri AP, Sontakke SD, Thawani VR, Saoji A, Goswami VS. Effects of Withania somnifera in patients of schizophrenia: a randomized, double blind, placebo controlled pilot trial study. Indian J Pharmacol. 2013;45(4):417-8. PubMed
  13. Biswal BM, Sulaiman SA, Ismail HC, Zakaria H, Musa KI. Effect of Withania somnifera (Ashwagandha) on the development of chemotherapy-induced fatigue and quality of life in breast cancer patients. Integr Cancer Ther. 2013;12(4):312-22.
  14. Sharma AK, Basu I, Singh S. Efficacy and safety of Ashwagandha root extract in subclinical hypothyroid patients: a double-blind, randomized placebo-controlled trial. J Altern Complement Med. 2018 Mar;24(3):243-248. PubMed
  15. Durg S, Bavage S, Shivaram SB. Withania somnifera (Indian ginseng) in diabetes mellitus: A systematic review and meta-analysis of scientific evidence from experimental research to clinical application. Phytother Res. 2020;34(5):1041-1059.
  16. Björnsson HK, Björnsson ES, Avula B, et al. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver Int. 2020;40(4):825-829. PubMed
  17. Tharakan A, Shukla H, Benny IR, Tharakan M, George L, Koshy S. Immunomodulatory Effect of Withania somnifera (Ashwagandha) Extract-A Randomized, Double-Blind, Placebo Controlled Trial with an Open Label Extension on Healthy Participants. J Clin Med 2021;1 PubMed
  18. Ireland PJ, Hardy T, Burt AD, Donnelly MC. Drug-induced hepatocellular injury due to herbal supplement ashwagandha. J R Coll Physicians Edinb. 2021;51(4):363-365. PubMed
  19. Kamal HI, Patel K, Brdak A, Heffernan J, Ahmad N. Ashwagandha as a unique cause of thyrotoxicosis presenting with supraventricular tachycardia. Cureus. 2022 Mar 25;14(3):e23494. PubMed
  20. Suryawanshi G, Abdallah M, Thomson M, Desai N, Chauhan A, Lim N. Ashwagandha-Associated Acute Liver Failure Requiring Liver Transplantation. Am J Ther 2023;30(1):e80-e83. PubMed
  21. Pusec CM, Wolsky R, Llerena C, Sura P. A Case of Supplement-Induced Hepatitis. Cureus 2022;14(10):e30433. PubMed
  22. Ajgaonkar A, Jain M, Debnath K. Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract for Improvement of Sexual Health in Healthy Women: A Prospective, Randomized, Placebo-Controlled Study. Cureus 2022;14(10):e30787. PubMed
  23. 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
  24. Lubarska M, Halasinski P, Hryhorowicz S, et al. Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury. Int J Environ Res Public Health 2023;20(5):3921. PubMed
  25. Tóth M, Benedek AE, Longerich T, Seitz HK. Ashwagandha-induced acute liver injury: A case report. Clin Case Rep 2023;11(3):e7078.
  26. Bokan G, Glamocanin T, Mavija Z, et al. Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. Pharmaceuticals (Basel) 2023;16(8):1129. PubMed
  27. Patel PA, Sanborn E, Then R, Williams DM. Recurrent Reversible Cerebral Vasoconstriction Syndrome: A Report of Two Cases. Cureus 2023;15(8):e42992. PubMed
  28. Majeed M, Nagabhushanam K, Murali A, Vishwanathan DT, Mamidala RV, Mundkur L. A Standardized Withania somniferra (Linn.) Root Extract with Piperine Alleviates the Symptoms of Anxiety and Depression by Increasing Serotonin Levels: A Double-Blind, Randomize
  29. Philips CA, Valsan A, Theruvath AH, et al. Ashwagandha-induced liver injury-A case series from India and literature review. Hepatol Commun 2023;7(10):e0270. PubMed
  30. Hayashi M, Hamada H, Azuma SI, Hayashi K. Painless Thyroiditis by Withania somnifera (Ashwagandha). Cureus 2024;16(3):e55352. PubMed
  31. Vazirani S, Kothari A, Fujimoto J, Gomez M. Supplements Are Not a Synonym for Safe: Suspected Liver Injury From Ashwagandha. Fed Pract 2023;40(9):315-319. PubMed
  32. Patel M, Newell R, Hillier M, Ramalingam R. Herbal remedies as a potential cause of hypoadrenalism. Br J Hosp Med (Lond) 2024;85(6):1-4. PubMed

See these in context on the Ashwagandha 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 →

Rhodiola 13 references
  1. Kim SH, Hyun SH, Choung SY. Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver of diabetic mice. Biofactors 2006;26:209-19.
  2. Kwon YI, Jang HD, Shetty K. Evaluation of Rhodiola crenulata and Rhodiola rosea for management of type II diabetes and hypertension. Asia Pac J Clin Nutr 2006;15:425-32.
  3. Bystritsky A, Kerwin L, Feusner JD. A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD). J Altern Complement Med 2008;14:175-80.
  4. Shevtsov VA, Zholus BI, Shervarly VI, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine 2003;10:95-105. PubMed
  5. Apostolidis E, Kwon YI, Shetty K. Potential of cranberry-based herbal synergies for diabetes and hypertension management. Asia Pac J Clin Nutr 2006;15:433-41.
  6. Hellum BH, Tosse A, Hoybakk K, et al. Potent in vitro inhibition of CYP3A4 and P-glycoprotein by Rhodiola rosea. Planta Med 2010;76:331-8.
  7. Skopriska-Rozewska E, Wojcik R, Siwicki AK, et al. The effect of Rhodiola quadrifida extracts on cellular immunity in mice and rats. Pol J Vet Sci 2008;11:105-11.
  8. Mishra KP, Chanda S, Shukla K, Ganju L. Adjuvant effect of aqueous extract of Rhodiola imbricate rhizome on the immune responses to tetanus toxoid and ovalbumin in rats. Immunopharmacol Immunotoxicol 2010;32:141-6.
  9. Li HX, Sze SC, Tong Y, Ng TB. Production of Th1- and Th2-dependent cytokines induced by the Chinese medicine herb, Rhodiola algida, on human peripheral blood monocytes. J Ethnopharmacol 2009;123:257-66. PubMed
  10. Mishra KP, Ganju L, Chanda S, et al. Aqueous extract of Rhodiola imbricate rhizome stimulates Toll-like receptor 4, granzyme-B and Th1 cytokines in vitro. Immunobiology 2009;214:27-31.
  11. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  12. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
  13. Woron J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol 2018;52(6):983-96. PubMed

See these in context on the Rhodiola monograph →

Antioxidants 1 reference
  1. Tenório MB, Ferreira RC, Moura FA, Bueno NB, Goulart MOF, Oliveira ACM. Oral antioxidant therapy for prevention and treatment of preeclampsia: Meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis. 2018 Sep;28(9):865-876. PubMed

See these in context on the Antioxidants monograph →

Rosemary 20 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Foster S, Tyler VE. Tyler's Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. 3rd ed., Binghamton, NY: Haworth Herbal Press, 1993.
  3. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  4. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  5. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  6. Cartier LC, Lehrer A, Malo JL. Occupational asthma caused by aromatic herbs. Allergy 1996;51:647-9. DOI
  7. Burkhard PR, Burkhardt K, Haenggeli CA, Landis T. Plant-induced seizures: reappearance of an old problem. J Neurol 1999;246:667-70. PubMed
  8. Swain AR, Dutton SP, Truswell AS. Salicylates in foods. J Am Diet.Assoc 1985;85(8):950-60. DOI
  9. Zhu BT, Loder DP, Cai MX, et al. Dietary administration of an extract from rosemary leaves enhances the liver microsomal metabolism of endogenous estrogens and decreases their uterotropic action in CD-1 mice. Carcinogenesis 1998;19(10):1821-7. PubMed
  10. Debersac P, Heydel JM, Amiot MJ, et al. Induction of cytochrome P450 and/or detoxication enzymes by various extracts of rosemary: description of specific patterns. Food Chem Toxicol 2001;39(9):907-18. PubMed
  11. Debersac P, Vernevaut MF, Amiot MJ, et al. Effects of a water-soluble extract of rosemary and its purified component rosmarinic acid on xenobiotic-metabolizing enzymes in rat liver. Food Chem Toxicol 2001;39(2):109-17. PubMed
  12. Lee JJ, Jin YR, Lee JH, et al. Antiplatelet activity of carnosic acid, a phenolic diterpene from Rosmarinus officinalis. Planta Med 2007;73(2):121-7.
  13. Yamamoto J, Yamada K, Naemura A, et al. Testing various herbs for antithrombotic effect. Nutrition 2005;21(5):580-7. PubMed
  14. Naemura A, Ura M, Yamashita T, et al. Long-term intake of rosemary and common thyme herbs inhibits experimental thrombosis without prolongation of bleeding time. Thromb Res 2008;122(4):517-22. PubMed
  15. Lee JJ, Jin YR, Lim Y, et al. Antiplatelet activity of carnosol is mediated by the inhibition of TXA2 receptor and cytosolic calcium mobilization. Vascul Pharmacol 2006;45:148-53. PubMed
  16. Bakirel, T., Bakirel, U., Keles, O. U., Ulgen, S. G., and Yardibi, H. In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits. J Ethnopharmacol 2-28-2008;116(1):64-73. PubMed
  17. Erenmemisoglu, A., Saraymen, R., and Ustun, S. Effect of a Rosmarinus officinalis leave extract on plasma glucose levels in normoglycaemic and diabetic mice. Pharmazie 1997;52(8):645-646.
  18. Valones MAA, Silva ICG, Gueiros LAM, Leão JC, Caldas AF Jr, Carvalho AAT. Clinical assessment of rosemary-based toothpaste (Rosmarinus officinalis Linn.): A randomized controlled double-blind study. Braz Dent J. 2019;30(2):146-151. PubMed
  19. Quirarte-Báez SM, Zamora-Perez AL, Reyes-Estrada CA, et al. A shortened treatment with rosemary tea (rosmarinus officinalis) instead of glucose in patients with diabetes mellitus type 2 (TSD). J Popul Ther Clin Pharmacol. 2019;26(4):e18-e28.
  20. Al Jamal A. Effect of rosemary (Rosmarinus officinalis) on lipid profiles and blood glucose in human diabetic patients (type-2). African J. Biochem. Res. 2014;8(8):147-50. DOI

See these in context on the Rosemary monograph →

Fulvic Acid 3 references
  1. Lu, FJ. Arsenic as a promoter in the effect of humic substances on plasma prothrombin time in vitro. Thromb Res 6-15-1990;58(6):537-541. PubMed
  2. Vucskits, AV, Hullar, I, Bersenyi, A, Andrasofszky, E, Kulcsar, M, Szabo, J. Effect of fulvic and humic acids on performance, immune response and thyroid function in rats. J Anim Physiol Anim Nutr (Berl) 2010;94(6):721-728. PubMed
  3. Gandy JJ, Meeding JP, Snyman JR, et al. Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid. Clin Pharmacol. 2012;4:7-11. PubMed

See these in context on the Fulvic Acid monograph →

Shilajit 8 references
  1. Sadeghi SMH, Hosseini Khameneh SM, Khodadoost M, et al. Efficacy of momiai in tibia fracture repair: A randomized double-blinded placebo-controlled clinical trial. J Altern Complement Med 2020;26(6):521-528.
  2. Losa F, Deidda M, Firinu D, Martino MLD, Barca MP, Giacco SD. Exercise-induced anaphylaxis with an Ayurvedic drug as cofactor: A case report. World J Clin Cases 2019;7(5):623-627. PubMed
  3. Biswas TK, Pandit S, Mondal S, et al. Clinical evaluation of spermatogenic activity of processed Shilajit in oligospermia. Andrologia 2010;42(1):48-56. PubMed
  4. Stavropoulos K, Sotiriadis A, Patoulias D, et al. Pseudohyperaldosteronism due to mumijo consumption during pregnancy: a licorice-like syndrome. Gynecol Endocrinol 2018;34(12):1019-1021. PubMed
  5. Ghezelbash B, Shahrokhi N, Khaksari M, Ghaderi-Pakdel F, Asadikaram G. Hepatoprotective effects of shilajit on high fat-diet induced non-alcoholic fatty liver disease (NAFLD) in rats. Horm Mol Biol Clin Investig 2020;41(1):/j/hmbci. PubMed
  6. Ghezelbash B, Shahrokhi N, Khaksari M, Asadikaram G, Shahrokhi M, Shirazpour S. Protective roles of shilajit in modulating resistin, adiponectin, and cytokines in rats with non-alcoholic fatty liver disease. Chin J Integr Med 2022;28(6):531-537. PubMed
  7. Jafari M, Forootanfar H, Ameri A, et al. Antioxidant, cytotoxic and hyperalgesia-suppressing activity of a native Shilajit obtained from Bahr Aseman mountains. Pak J Pharm Sci 2019;32(5):2167-2173. DOI
  8. Trivedi NA, Mazumdar B, Bhatt JD, Hemavathi KG. Effect of shilajit on blood glucose and lipid profile in alloxan-induced diabetic rats. Ind. J. Pharmacol. 2004; 36(6):373-376.

See these in context on the Shilajit monograph →

Lion's Mane Mushroom 6 references
  1. Product information for <em>Niaspan</em>. Abbott Laboratories. North Chicago, IL 60064. April 2015.
  2. Liang B, Guo Z, Xie F, Zhao A. Antihyperglycemic and antihyperlipidemic activities of aqueous extract of Hericium erinaceus in experimental diabetic rats. BMC Complement Altern Med. 2013;13:253. PubMed
  3. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res. 2009;23(3):367-72.
  4. Mori K, Kikuchi H, Obara Y, et al. Inhibitory effect of hericenone B from Hericium erinaceus on collagen-induced platelet aggregation. Phytomedicine. 2010;17(14):1082-5. PubMed
  5. Li IC, Chang HH, Lin CH, et al. Prevention of early Alzheimer's disease by erinacine A-enriched Hericium erinaceus mycelia pilot double-blind placebo-controlled study. Front Aging Neurosci 2020 Jun 3;12:155. doi: 10.3389/fnagi.2020.00155. PubMed
  6. Tian B, Liu R, Xu T, et al. Modulating effects of Hericium erinaceus polysaccharides on the immune response by regulating gut microbiota in cyclophosphamide-treated mice. J Sci Food Agric 2023;103(6):3050-3064.

See these in context on the Lion's Mane Mushroom 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 →

Coenzyme Q10 40 references
  1. Kamikawa T, Kobayashi A, Yamashita T, et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol 1985;56:247-51. PubMed
  2. Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med 1994;S265-72. PubMed
  3. Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet 1994;334:1372-3. PubMed
  4. Singh RB, Niaz MA, Rastogi SS, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999;13:203-8. PubMed
  5. Portakal O, Ozkaya O, Erden Inal M, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-84. PubMed
  6. Lund EL, Quistorff B, Spang-Thomsen M, Kristjansen PE. Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol (Praha) 1998;43:505-6. PubMed
  7. Langsjoen PH, Langsjoen PH, Folkers K. Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy. Am J Cardiol 1990;65:521-3. PubMed
  8. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7. DOI
  9. Landbo C, Almdal TP. [Interaction between warfarin and coenzyme Q10]. Ugeskr Laeger 1998;160:3226-7.
  10. Baggio E, Gandini R, Plauncher AC, et al. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 1994;15 Suppl:S287-94. PubMed
  11. Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J 2001;94:1112-7. PubMed
  12. The Huntington Study Group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurology 2001;57:397-404.
  13. Hodgson JM, Watts GF, Playford DA, et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002;56:1137-42. PubMed
  14. Singh RB, Neki NS, Kartikey K, et al. Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. Mol Cell Biochem 2003;246:75-82. DOI
  15. Porterfield LM. Why did the response to warfarin change? RN 2000;63:107.
  16. Sandor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial. Neurology 2005;64:713-5. PubMed
  17. 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
  18. Berman M, Erman A, Ben-Gal T, et al. Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study. Clin Cardiol 2004;27:295–9. PubMed
  19. Storch A, Jost WH, Vieregge P, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol 2007;64:938-44. DOI
  20. Digiesi V, Cantini F, Oradei A, et al. Coenzyme Q10 in essential hypertension. Mol Aspects Med 1994;15 Suppl:s257-63. PubMed
  21. Yamagami T, Takagi M, Akagami H, et al. Effect of coenzyme Q10 on essential hypertension, a double blind controlled study. In: Folkers KA, Yamamura Y, eds. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 5. Amsterdam: Elsevier Science Publications, 19
  22. Ho MJ, Bellusci A, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension (review). Cochrane Database Syst Rev 2009;(4):CD007435. PubMed
  23. Rosenfeldt, F. L., Haas, S. J., Krum, H., Hadj, A., Ng, K., Leong, J. Y., and Watts, G. F. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum.Hypertens. 2007;21(4):297-306. PubMed
  24. Stamelou, M., Reuss, A., Pilatus, U., Magerkurth, J., Niklowitz, P., Eggert, K. M., Krisp, A., Menke, T., Schade-Brittinger, C., Oertel, W. H., and Hoglinger, G. U. Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, place DOI
  25. Keogh A, Fenton S, Leslie C, et al. Randomised double-blind, placebo-controlled trial of coenzyme Q, therapy in class II and III systolic heart failure. Heart Lung Circ. 2003;12:135-41.
  26. Gane, E. J., Weilert, F., Orr, D. W., Keogh, G. F., Gibson, M., Lockhart, M. M., Frampton, C. M., Taylor, K. M., Smith, R. A., and Murphy, M. P. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C
  27. Lynch, D. R., Perlman, S. L., and Meier, T. A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia. Arch Neurol. 2010;67(8):941-947. PubMed
  28. Young, J. M., Florkowski, C. M., Molyneux, S. L., McEwan, R. G., Frampton, C. M., Nicholls, M. G., Scott, R. S., and George, P. M. A randomized, double-blind, placebo-controlled crossover study of coenzyme Q10 therapy in hypertensive patients with the me
  29. Ishiyama, T., Morita, Y., Toyama, S., Yamagami, T., and Tsukamoto, N. A clinical study of the effect of coenzyme Q on congestive heart failure. Jpn.Heart J 1976;17(1):32-42. PubMed
  30. Matthews, P. M., Ford, B., Dandurand, R. J., Eidelman, D. H., O'Connor, D., Sherwin, A., Karpati, G., Andermann, F., and Arnold, D. L. Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease. Neurology 1993;43(5
  31. Malm, C., Svensson, M., Sjoberg, B., Ekblom, B., and Sjodin, B. Supplementation with ubiquinone-10 causes cellular damage during intense exercise. Acta Physiol Scand. 1996;157(4):511-512. PubMed
  32. Singh, R. B., Wander, G. S., Rastogi, A., Shukla, P. K., Mittal, A., Sharma, J. P., Mehrotra, S. K., Kapoor, R., and Chopra, R. K. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc. PubMed
  33. Digiesi V, Cantini F, and Brodbeck B. Effect of coenzyme Q10 on essential arterial hypertension. Current Therapeutic Research 1990;47(5):841-845.
  34. Parkinson Study Group QE3 Investigators, Beal MF, Oakes D, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014;71(5):543-52.
  35. Alehagen U, Johansson P, Bjornstedt M, et al. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citi
  36. Ho MJ, Li EC, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane Database Syst Rev. 2016 Mar 3;3:CD007435. doi: 10.1002/14651858.CD007435.pub3. PubMed
  37. Tabrizi R, Akbari M, Sharifi N, Lankarani KB, Moosazadeh M, Kolahdooz F, et al. The effects of coenzyme Q10 supplementation on blood pressures among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials. PubMed
  38. Tsai IC, Hsu CW, Chang CH, Tseng PT, Chang KV. Effectiveness of coenzyme Q10 supplementation for reducing fatigue: A systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 2022;13:883251. PubMed
  39. Yaghini O, Hoseini N, Ghazavi MR, et al. A comparative study on the efficacy of coenzyme Q10 and amitriptyline in the prophylactic treatment of migraine headaches in children: A randomized controlled trial. Adv Biomed Res 2022;11:43. PubMed
  40. Hansen KS, Mogensen TH, Agergaard J, et al. High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: A randomized, phase 2, crossover trial. Lancet Reg Health Eur 2022. PubMed

See these in context on the Coenzyme Q10 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 →

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 →

Sodium 38 references
  1. Garabedian-Ruffalo SM, Ruffalo RL. Drug and nutrient interactions. Am Fam Physician 1986;33:165-74.
  2. Food and Drug Administration Science Background: Safety of Sodium Phosphates Oral Solution. September 17, 2001. Available at: http://www.fda.gov/cder/drug/safety/sodiumphospate.htm
  3. Coton T, Mallaret C, Coilliot C, Carre D, Guisset M. Severe acute ulcerated gastritis induced by salt. Presse Med 2009;38(3):499-500. PubMed
  4. Frings-Meuthen P, Buehlmeier J, Baecker N, et al. High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses. J Appl Physiol 2011;111(2):537-542. PubMed
  5. Frings-Meuthen P, Baecker N, Heer M. Low-grade metabolic acidosis may be the cause of sodium chloride-induced exaggerated bone resorption. J Bone Miner Res 2008;23(4):517-524. PubMed
  6. Alam S, Johnson AG. A meta-analysis of randomised controlled trials (RCT) among healthy normotensive and essential hypertensive elderly patients to determine the effect of high salt (NaCl) diet of blood pressure. J Hum Hypertens 1999;13(6):367-74.
  7. Boudville N, Ward S, Benaroia M, House AA. Increased sodium intake correlates with greater use of antihypertensive agents by subjects with chronic kidney disease. Am J Hypertens 2005;18(10):1300-5. PubMed
  8. Bennett WM. Drug interactions and consequences of sodium restriction. Am J Clin Nutr 1997;65(2 Suppl):678S-681S. PubMed
  9. Okusa MD, Crystal LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med 1994;97(4):383-9. PubMed
  10. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for water, potassium, sodium, chloride, and sulfate. Washington, DC: National Academy Press, 2005. Available at: http://www.nap.edu/openbook.php?record_id=10925. DOI
  11. D'Elia L, Rossi G, Ippolito R, Cappuccio FP, Strazzullo P. Habitual salt intake and risk of gastric cancer: a meta-analysis of prospective studies. Clin Nutr 2012;31(4):489-98. PubMed
  12. Goldsmith SR. Hyponatremia in heart failure: time for a trial. J Card Fail 2013;19(6):398-400. PubMed
  13. Willocks L, Brettle R, Keen J, Valentine C, Pinching AJ. Formulations of didanosine (ddI) and salt overload. Lancet 1992;339(8786):190.
  14. Chen L, Zhang Z, Chen W, Whelton PK, Appel LJ. Lower Sodium Intake and Risk of Headaches: Results From the Trial of Nonpharmacologic Interventions in the Elderly. Am J Public Health. 2016;106(7):1270-5. PubMed
  15. Cook NR, Appel LJ, Whelton PK. Lower levels of sodium intake and reduced cardiovascular risk. Circulation. 2014;129(9):981-9. PubMed
  16. Cook NR, Appel LJ, Whelton PK. Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention. J Am Coll Cardiol. 2016;68(15):1609-1617. PubMed
  17. Mente A, O'Donnell M, Rangarajan S, et al. Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies. Lancet. 2016;388(10043):465-75. PubMed
  18. Moosavian SP, Haghighatdoost F, Surkan PJ, Azadbakht L. Salt and obesity: a systematic review and meta-analysis of observational studies. Int J Food Sci Nutr. 2017;68(3):265-277. PubMed
  19. O'Donnell M, Mente A, Rangarajan S, et al. Urinary sodium and potassium excretion, mortality, and cardiovascular events. N Engl J Med. 2014;371(7):612-23. DOI
  20. Poggio R, Gutierrez L, Matta MG, Elorriaga N, Irazola V, Rubinstein A. Daily sodium consumption and CVD mortality in the general population: systematic review and meta-analysis of prospective studies. Public Health Nutr. 2015;18(4):695-704. PubMed
  21. Stallings VA, Harrison M, Oria M; Committee to Review the Dietary Reference Intakes for Sodium and Potassium, Food and Nutrition Board, Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine. Washington (DC): National Acad
  22. Mahtani KR, Heneghan C, Onakpoya I, et al. Reduced Salt Intake for Heart Failure: A Systematic Review. JAMA Intern Med. 2018 Dec 1;178(12):1693-1700. PubMed
  23. Yancy CW. Sodium Restriction in Heart Failure: Too Much Uncertainty-Do the Trials. JAMA Intern Med. 2018 Dec 1;178(12):1700-1701. PubMed
  24. He FJ, Campbell NRC, Ma Y, MacGregor GA, Cogswell ME, Cook NR. Errors in estimating usual sodium intake by the Kawasaki formula alter its relationship with mortality: implications for public health. Int J Epidemiol. 2018;47(6):1784-1795. PubMed
  25. Murthy K, Ondrey GJ, Malkani N, et al. THE EFFECTS OF HYPONATREMIA ON BONE DENSITY AND FRACTURES: A SYSTEMATIC REVIEW AND META-ANALYSIS. Endocr Pract. 2019;25(4):366-378. PubMed
  26. Messerli FH, Hofstetter L, Syrogiannouli L, et al. Sodium intake, life expectancy, and all-cause mortality. Eur Heart J 2021;42(21):2103-2112. PubMed
  27. Graudal NA, Hubeck-Graudal T, Jurgens G. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride. Cochrane Database Syst Rev 2020;12(12):CD004022. PubMed
  28. Giatti S, Santos RB, Aielo AN, et al. Association of sodium with obstructive sleep apnea. The ELSA-Brasil study. Ann Am Thorac Soc 2021;18(3):502-510. PubMed
  29. Nan X, Lu H, Wu J, et al. The interactive association between sodium intake, alcohol consumption and hypertension among elderly in northern China: a cross-sectional study. BMC Geriatr 2021;21(1):135. PubMed
  30. Kyozuka H, Fukusda T, Murata T, et al. Impact of preconception sodium intake on hypertensive disorders of pregnancy: The Japan Environment and Children's study. Pregnancy Hypertens 2021;23:66-72. PubMed
  31. Zhao L, Ogden CL, Yang Q, et al. Association of usual sodium intake with obesity among US children and adolescents, NHANES 2009-2016. Obesity (Silver Spring) 2021;29(3):587-594. PubMed
  32. Ma Y, He FJ, Sun Q, et al. 24-Hour urinary sodium and potassium excretion and cardiovascular risk. N Engl J Med 2022;386(3):252-263. PubMed
  33. Liu J, Yang X, Zhang P, et al. Association of urinary sodium excretion and left ventricular hypertrophy in people with type 2 diabetes mellitus: A cross-sectional study. Front Endocrinol (Lausanne) 2021;12:728493. PubMed
  34. Filippini T, Malavolti M, Whelton PK, Vinceti M. Sodium intake and risk of hypertension: A systematic review and dose-response meta-analysis of observational cohort studies. Curr Hypertens Rep 2022;24(5):133-144. PubMed
  35. Wang DD, Li Y, Nguyen XT, et al. Dietary sodium and potassium intake and risk of non-fatal cardiovascular diseases: The million veteran program. Nutrients 2022;14(5):1121. PubMed
  36. Kwak JH, Park CH, Eun CS, et al. The associations of dietary intake of high sodium and low zinc with gastric cancer mortality: A prospective cohort study in Korea. Nutr Cancer 2022;74(10):3501-3508. PubMed
  37. George S, Maiti R, Mishra BR, Jena M, Mohapatra D. Effect of regulated add-on sodium chloride intake on stabilization of serum lithium concentration in bipolar disorder: A randomized controlled trial. Bipolar Disord 2023;25(1):66-75. PubMed
  38. Zhou TL, Schütten MTJ, Kroon AA, et al. Urinary Sodium Excretion and Salt Intake Are Not Associated With Blood Pressure Variability in a White General Population. J Am Heart Assoc 2023;12(1):e026578. PubMed

See these in context on the Sodium monograph →

Magnesium 82 references
  1. Rodin SM, Johnson BF. Pharmacokinetic interactions with digoxin. Clin Pharmacokinet 1988;15:227-44.
  2. Covington TR, et al. Handbook of Nonprescription Drugs. 11th ed. Washington, DC: American Pharmaceutical Association, 1996.
  3. Dahle LO, Berg G, Hammar M, et al. The effect of oral magnesium substitution on pregnancy-induced leg cramps. Am J Obstet Gynecol 1995;173:175-80. PubMed
  4. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  5. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996;16:257-63. PubMed
  6. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1999. Available at: http://books.nap.edu/books/0309063507/html/index.html.
  7. Birrer RB, Shallash AJ, Totten V. Hypermagnesemia-induced fatality following epsom salt gargles. J Emerg Med 2002;22:185-8. PubMed
  8. Ryan MP. Diuretics and potassium/magnesium depletion. Directions for treatment. Am J Med 1987;82:38-47.. PubMed
  9. Hollifield JW. Magnesium depletion, diuretics, and arrhythmias. Am J Med 1987;82:30-7.. PubMed
  10. Heidenreich O. Mode of action of conventional and potassium-sparing diuretics--aspects with relevance to Mg-sparing effects. Magnesium 1984;3:248-56..
  11. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study. Cephalalgia 1996;16:436-40.. PubMed
  12. Wang F, Van Den Eeden SK, Ackerson LM, et al. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache 2003;43:601-10.. PubMed
  13. Sompolinsky D, Samra Z. Influence of magnesium and manganese on some biological and physical properties of tetracycline. J Bacteriol 1972;110:468-76.. PubMed
  14. Jeyabalan A, Caritis SN. Pharmacologic inhibition of preterm labor. Clin Obstet Gynecol 2002;45:99-113. PubMed
  15. Mittendorf R, Dambrosia J, Pryde PG, et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol 2002;186:1111-8.. PubMed
  16. Witlin AG, Sibai BM. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol 1998;92:883-9.. DOI
  17. Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev 2002;4:CD001060. . PubMed
  18. Davey MJ, Teubner D. A randomized controlled trial of magnesium sulfate, in addition to usual care, for rate control in atrial fibrillation. Ann Emerg Med 2005;45:347-53.. PubMed
  19. L'Hommedieu CS, Nicholas D, Armes DA, et al. Potentiation of magnesium sulfate--induced neuromuscular weakness by gentamicin, tobramycin, and amikacin. J Pediatr 1983;102:629-31..
  20. Dunn CJ, Goa KL. Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. Drugs 2001;61:685-712..
  21. Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr 2012;66:411-8. PubMed
  22. Koontz SL, Friedman SA, Schwartz ML. Symptomatic hypocalcemia after tocolytic therapy with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 2004;190(6):1773-6. PubMed
  23. Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 1989;161(1):35-6. PubMed
  24. Waisman GD, Mayorga LM, Cámera MI, et al. Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia? Am J Obstet Gynecol. 1988;159(2):308-9. PubMed
  25. Brown DD, Juhl RP. Decreased bioavailability of digoxin due to antacids and kaolin-pectin. N Engl J Med. 1976;295(19):1034-7. PubMed
  26. Allen MD, Greenblatt DJ, Harmatz JS, et al. Effect of magnesium--aluminum hydroxide and kaolin--pectin on absorption of digoxin from tablets and capsules. J Clin Pharmacol. 1981;21(1):26-30. PubMed
  27. Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an in vitro study. Thromb Haemost. 1996;76(1):88-93. DOI
  28. Ravn HB, Kristensen SD, Vissinger H, et al. Magnesium inhibits human platelets. Blood Coagul Fibrinolysis. 1996;7(2):241-4. PubMed
  29. Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an infusion study in healthy volunteers. Thromb Haemost. 1996;75(6):939-44. DOI
  30. Neuvonen PJ, Kivistö KT. The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations. Br J Clin Pharmacol. 1991;32(2):215-20. PubMed
  31. Kivistö KT, Neuvonen PJ. Enhancement of absorption and effect of glipizide by magnesium hydroxide. Clin Pharmacol Ther. 1991;49(1):39-43. PubMed
  32. Neuvonen PJ, Kivistö KT. Enhancement of drug absorption by antacids. An unrecognised drug interaction. Clin Pharmacokinet. 1994;27(2):120-8. PubMed
  33. Shechter, M., Merz, C. N., Paul-Labrador, M., Meisel, S. R., Rude, R. K., Molloy, M. D., Dwyer, J. H., Shah, P. K., and Kaul, S. Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart
  34. Ganzevoort, J. W., Hoogerwaard, E. M., and van der Post, J. A. [Hypocalcemic delirium due to magnesium sulphate therapy in a pregnant woman with pre-eclampsia]. Ned.Tijdschr.Geneeskd. 8-3-2002;146(31):1453-1456.
  35. Horner, S. M. Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction. Circulation 1992;86(3):774-779. PubMed
  36. Azria, E., Tsatsaris, V., Goffinet, F., Kayem, G., Mignon, A., and Cabrol, D. [Magnesium sulfate in obstetrics: current data]. J Gynecol.Obstet.Biol.Reprod.(Paris) 2004;33(6 Pt 1):510-517.
  37. Magee, L. A., Miremadi, S., Li, J., Cheng, C., Ensom, M. H., Carleton, B., Cote, A. M., and von Dadelszen, P. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with p
  38. Henyan, N. N., Gillespie, E. L., White, C. M., Kluger, J., and Coleman, C. I. Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis. Ann.Thorac.Surg. 2005;80(6):2402-2406. PubMed
  39. Li, J., Zhang, Q., Zhang, M., and Egger, M. Intravenous magnesium for acute myocardial infarction. Cochrane.Database.Syst.Rev. 2007;(2):CD002755. PubMed
  40. Doyle, L. W., Crowther, C. A., Middleton, P., Marret, S., and Rouse, D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane.Database.Syst.Rev. 2009;(1):CD004661. PubMed
  41. Han, S., Crowther, C. A., and Moore, V. Magnesium maintenance therapy for preventing preterm birth after threatened preterm labour. Cochrane.Database.Syst.Rev. 2010;(7):CD000940. PubMed
  42. Duley, L., Gulmezoglu, A. M., Henderson-Smart, D. J., and Chou, D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane.Database.Syst.Rev. 2010;(11):CD000025. PubMed
  43. Conde-Agudelo, A., Romero, R., and Kusanovic, J. P. Nifedipine in the management of preterm labor: a systematic review and metaanalysis. Am J Obstet.Gynecol. 2011;204(2):134-20. PubMed
  44. Wong, G. K., Boet, R., Poon, W. S., Chan, M. T., Gin, T., Ng, S. C., and Zee, B. C. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis. Crit Care 2011;15(1):R52. PubMed
  45. Magee, L., Sawchuck, D., Synnes, A., and von, Dadelszen P. SOGC Clinical Practice Guideline. Magnesium sulphate for fetal neuroprotection. J Obstet.Gynaecol.Can. 2011;33(5):516-529.
  46. Doyle, L. W. Antenatal magnesium sulfate and neuroprotection. Curr Opin Pediatr 2012;24(2):154-159. PubMed
  47. McDonald, S. D., Lutsiv, O., Dzaja, N., and Duley, L. A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use. Int J Gynaecol.Obstet. 2012;118(2):90-96. PubMed
  48. Gordon, M., Naidoo, K., Akobeng, A. K., and Thomas, A. G. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane.Database.Syst.Rev. 2012;7:CD009118. PubMed
  49. Dodd, J. M., Crowther, C. A., and Middleton, P. Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane.Database.Syst.Rev. 2012;12:CD003927. PubMed
  50. Wu, X., Wang, C., Zhu, J., Zhang, C., Zhang, Y., and Gao, Y. Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting. BMC.Cardiovasc.D PubMed
  51. Thorp, J. M., Jr., Katz, V. L., Campbell, D., and Cefalo, R. C. Hypersensitivity to magnesium sulfate. Am.J.Obstet.Gynecol. 1989;161(4):889-890. PubMed
  52. Duley L and Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. Cochrane Database of Systematic Reviews 2000;(3) PubMed
  53. Gibbins KJ, Browning KR, Lopes VV, Anderson BL, Rouse DJ. Evaluation of the clinical use of magnesium sulfate for cerebral palsy prevention. Obstet Gynecol 2013;121(2 Pt 1):235-40. PubMed
  54. Ji D. Oral magnesium sulfate causes perforation during bowel preparation for fiberoptic colonoscopy in patients with colorectal cancer. J Emerg Med 2012;43(4):716-7. PubMed
  55. Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet 2012;27(2):248-54. PubMed
  56. Yamasaki M, Funakoshi S, Matsuda S, Imazu T, Takeda Y, Murakami T, Maeda Y. Interaction of magnesium oxide with gastric acid secretion inhibitors in clinical pharmacotherapy. Eur J Clin Pharmacol 2014;70(8):921-4. PubMed
  57. Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, Do SH. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth. 2017 Feb;36:102-106. PubMed
  58. Ikee R, Toyoyama T, Endo T, Tsunoda M, Hashimoto N. Impact of sevelamer hydrochloride on serum magnesium concentrations in hemodialysis patients. Magnes Res. 2016 Apr 1;29(4):184-90. PubMed
  59. Miller ES, Sakowicz A, Leger E. Lange E, Yee LM. The association between receipt of intrapartum magnesium and postpartum hemorrhage. Am J Obstet Gynecol 2018;218(1 Suppl):S165.
  60. Rodríguez-Rubio L, Solis Garcia Del Pozo J, Nava E, Jordán J. Interaction between magnesium sulfate and neuromuscular blockers during the perioperative period. A systematic review and meta-analysis. J Clin Anesth. 2016;34:524-34. PubMed
  61. Brown RS. Magnesium Sulfate: Another Cause of a Solute Diuresis. Am J Kidney Dis. 2017;69(4):550-551. PubMed
  62. Park H, Qin R, Smith TJ, et al. North Central Cancer Treatment Group N10C2 (Alliance): a double-blind placebo-controlled study of magnesium supplements to reduce menopausal hot flashes. Menopause. 2015;22(6):627-32. PubMed
  63. Sakanoue M, Sanada J, Kanekura T. Skin eruption elicited by magnesium oxide (Maglax). J Dermatol. 2016;43(2):221-2.
  64. Iwamuro M, Saito S, Yoshioka M, et al. A Magnesium Oxide Bezoar. Intern Med. 2018;57(21):3087-3091. PubMed
  65. Vilchez G, Dai J, Kumar K, Mundy D, Kontopoulos E, Sokol RJ. Racial/ethnic disparities in magnesium sulfate neuroprotection: a subgroup analysis of a multicenter randomized controlled trial. J Matern Fetal Neonatal Med. 2018;31(17):2304-2311. PubMed
  66. Drug Safety Communication: FDA Recommends Against Prolonged Use of Magnesium Sulfate to Stop Pre-term Labor Due to Bone Changes in Exposed Babies. U.S. Food and Drug Administration (FDA), May 30, 2013. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM353
  67. Committee Opinion: Magnesium Sulfate Use in Obstetrics. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for Maternal-Fetal Medicine, Number 652, January 2016. https://www.acog.org/Clinical-Guidance-and-Publi
  68. Kashihara Y, Terao Y, Yoda K, et al. Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. Eur J Clin Pharmacol. 2019;75(3):351-361. PubMed
  69. Shepherd E, Salam RA, Manhas D, et al. Antenatal magnesium sulphate and adverse neonatal outcomes: A systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002988. PubMed
  70. Hong JY, Hong JY, Choi YS, et al. Antenatal magnesium sulfate treatment and risk of necrotizing enterocolitis in preterm infants born at less than 32 weeks of gestation. Sci Rep. 2020;10(1):12826. PubMed
  71. Schuh S, Sweeney J, Rumantir M, et al. Effect of nebulized magnesium vs placebo added to albuterol on hospitalization among children with refractory acute asthma treated in the emergency department: a randomized clinical trial. JAMA. 2020;324(20):2038-20 PubMed
  72. Almeida CED, Carvalho LR, Andrade CVC, Nascimento PD Jr, Barros GAM, Modolo NSP. Effects of magnesium sulphate on the onset time of rocuronium at different doses: a randomized clinical trial. Braz J Anesthesiol. 2021;71(5):482-8. PubMed
  73. Gochi Valdovinos A, Arriaga-Redondo M, Dejuan Bitriá E, Pérez Rodríguez I, Márquez Isidro E, Blanco Bravo D. Prenatal therapy with magnesium sulphate and intestinal obstruction due to meconium in preterm newborns. An Pediatr (Engl Ed). 2022 Feb;96(2):138- PubMed
  74. Iio K, Kondo E, Shibata E, et al. Long-term tocolysis with magnesium sulfate as a risk factor for low bone mass: a case series. J Med Cases. 2022 Feb;13(2):47-50. PubMed
  75. Eiraku K, Uozumi Y, Hieda M, Maruyama T, Nomura H. A senile case of heart failure associated with hypermagnesemia induced by magnesium-containing laxative agent. Geriatr Gerontol Int. 2022;22(10):897-899.
  76. Enayati A, Gin JH, Sajeev JK, et al. Efficacy of intravenous magnesium for the management of non-post operative atrial fibrillation with rapid ventricular response: A systematic review and meta-analysis. J Cardiovasc Electrophysiol 2023;34(5):1286-1295. PubMed
  77. Su YH, Luo DC, Pang Y. Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study. BMC Anesthesiol 2023;23(1):326. PubMed
  78. Han J, Park HY, Shin HJ, Chung SH, Do SH. Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial. Magnes Res 2023;36(2):31-39. PubMed
  79. Lee AT, Cordova JC, Jamplis RP, Pomicter GR. Posterior Reversible Encephalopathy Syndrome and Eclampsia in the Setting of Magnesium Toxicity: A Case Report. A A Pract 2023;17(11):e01726. PubMed
  80. Darmawan D, Rengganis I, Rumende CM, et al. Effectiveness and Safety of Nebulized Magnesium as Last Line Treatment in Adults with Acute Asthma Attack: A Systematic Review and Meta-Analysis. Acta Med Indones 2024;56(1):3-12.
  81. Shepherd ES, Goldsmith S, Doyle LW, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2024;5(5):CD004661. PubMed
  82. 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 Magnesium monograph →

Sceletium 3 references
  1. Smith MT, Crouch NR, Gericke N, Hirst M. Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review. J Ethnopharmacol 1996;50:119-30. PubMed
  2. Meyer GMJ, Wink CSD, Zapp J, Maurer HH. GC-MS, LC-MS(n), LC-high resolution-MS(n), and NMR studies on the metabolism and toxicological detection of mesembrine and mesembrenone, the main alkaloids of the legal high "Kanna" isolated from Sceletium tortuosum
  3. Gericke J, Lekhooa M, Steyn SF, Viljoen AM, Harvey BH. An acute dose-ranging evaluation of the antidepressant properties of Sceletium tortuosum (Zembrin®) versus escitalopram in the Flinders Sensitive Line rat. J Ethnopharmacol. 2022 Feb 10;284:114550. do PubMed

See these in context on the Sceletium monograph →

Coleus 16 references
  1. Baumann G, Felix S, Sattelberger U, Klein G. Cardiovascular effects of forskolin (HL-362) in patients with idiopathic congestiv cardiomyopathy. A comparative study with dobutamine and sodium nitroprusside. J Cardiovasc Pharmacol 1990;16:93-100.
  2. Kramer W, Thormann J, Kindler M, Schlepper M. Effects of forskolin on left ventricular function in dilated cardiomyopathy. Arzneimittelforschung 1987;37:364-7.
  3. Bauer K, Dietersdorfer F, Kaspar S, et al. Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma. Clin Pharmacol Ther 1993;53:76-83. PubMed
  4. Christenson JT, Thulesius O, Nazzal MM. The effect of forskolin on blood flow, platelet metabolism, aggregation and ATP release. Vasa 1995;24:56-61.
  5. Agarwal KC, Zielinski BA, Maitra RS. Significance of plasma adenosine in the antiplatelet activity of forskolin: potentiation by dipyridamole and dilazep. Thromb Haemost 1989;61:106-10. DOI
  6. Agarwal KC, Parks RE. Forskolin: a potential antimetastatic agent. Int J Cancer 1983;32:801-4. PubMed
  7. Almeida, F. C. and Lemonica, I. P. The toxic effects of Coleus barbatus B. on the different periods of pregnancy in rats. J Ethnopharmacol 2000;73(1-2):53-60. PubMed
  8. Ding, X. and Staudinger, J. L. Induction of drug metabolism by forskolin: the role of the pregnane X receptor and the protein kinase a signal transduction pathway. J Pharmacol Exp Ther 2005;312(2):849-856. PubMed
  9. Staudinger, J. L., Ding, X., and Lichti, K. Pregnane X receptor and natural products: beyond drug-drug interactions. Expert.Opin Drug Metab Toxicol 2006;2(6):847-857. PubMed
  10. van Hecke, E., Hindryckx, P., Geuns, J. M., and Devriese, E. Airborne contact dermatitis from coleus in a housewife. Contact Dermatitis 1991;25(2):128-129. PubMed
  11. Schlepper, M., Thormann, J., and Mitrovic, V. Cardiovascular effects of forskolin and phosphodiesterase-III inhibitors. Basic Res Cardiol 1989;84 Suppl 1:197-212. PubMed
  12. Dooms-Goossens, A., Borghijs, A., Degreef, H., Devriese, E. G., and Geuns, J. M. Airborne contact dermatitis to Coleus. Contact Dermatitis 1987;17(2):109-110. PubMed
  13. Lindner, E., Dohadwalla, A. N., and Bhattacharya, B. K. Positive inotropic and blood pressure lowering activity of a diterpene derivative isolated from Coleus forskohli: Forskolin. Arzneimittelforschung 1978;28(2):284-289.
  14. Loftus HL, Astell KJ, Mathai ML, et al. Coleus forskohlii Extract Supplementation in Conjunction with a Hypocaloric Diet Reduces the Risk Factors of Metabolic Syndrome in Overweight and Obese Subjects: A Randomized Controlled Trial. Nutrients. 2015;7(11): PubMed
  15. Yokotani K, Chiba T, Sato Y, et al. Hepatic cytochrome P450 mediates interaction between warfarin and Coleus forskohlii extract in vivo and in vitro. J Pharm Pharmacol. 2012;64(12):1793-801.
  16. Nishijima C, Chiba T, Sato Y, Umegaki K. Nationwide Online Survey Enables the Reevaluation of the Safety of Coleus forskohlii Extract Intake Based on the Adverse Event Frequencies. Nutrients. 2019;11(4). pii: E866. PubMed

See these in context on the Coleus 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 →

Theacrine 1 reference
  1. Xu JK, Kurihara H, Zhao L, Yao XS. Theacrine, a special purine alkaloid with sedative and hypnotic properties from Cammelia assamica var. kucha in mice. J Asian Nat Prod Res 2007;9(6-8):665-72.

See these in context on the Theacrine 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 →

Ergothioneine 2 references
  1. Benson KF, Ager DM, Landes B, Aruoma OI, Jensen GS. Improvement of joint range of motion (ROM) and reduction of chronic pain after consumption of an ergothioneine-containing nutritional supplement. Prev Med. 2012;54 Suppl:S83-9. PubMed
  2. Smith E, Ottosson F, Hellstrand S, et al. Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. Heart 2019. pii: heartjnl-2019-315485. PubMed

See these in context on the Ergothioneine 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 →

Deer Velvet 2 references
  1. Sleivert, G., Burke, V., Palmer, C., Walmsley, A., Gerrard, D., Haines, S., and Littlejohn, R. The effects of deer antler velvet extract or powder supplementation on aerobic power, erythropoiesis, and muscular strength and endurance characteristics. Int PubMed
  2. Bubenik, G. A., Miller, K. V., Lister, A. L., Osborn, D. A., Bartos, L., and van der Kraak, G. J. Testosterone and estradiol concentrations in serum, velvet skin, and growing antler bone of male white-tailed deer. J Exp Zoolog.A Comp Exp Biol 3-1-2005;30 PubMed

See these in context on the Deer Velvet monograph →

Citicoline 11 references
  1. Spiers PA, Myers D, Hochanadel GS, et al. Citicoline improves verbal memory in aging. Arch Neurol 1996;53:441-8. PubMed
  2. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev 2005;(2):CD000269. PubMed
  3. Conant R, Schauss AG. Therapeutic applications of citicoline for stroke and cognitive function in the elderly: A review of the literature. Altern Med Rev 2004;9:17-31.
  4. Warach, S., Pettigrew, L. C., Dashe, J. F., Pullicino, P., Lefkowitz, D. M., Sabounjian, L., Harnett, K., Schwiderski, U., and Gammans, R. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 0 DOI
  5. Lukas, S. E., Kouri, E. M., Rhee, C., Madrid, A., and Renshaw, P. F. Effects of short-term citicoline treatment on acute cocaine intoxication and cardiovascular effects. Psychopharmacology.(Berl.) 2001;157(2):163-167. PubMed
  6. Dinsdale, J. R., Griffiths, G. K., Castello, J., Maddock, J., Ortiz, J. A., and Aylward, M. CDP-choline: repeated oral dose tolerance studies in adult healthy volunteers. Arzneimittelforschung. 1983;33(7A):1061-1065.
  7. Clark BC, Georgekutty J, Berul CI. Myocardial ischemia secondary to synthetic cannabinoid (K2) use in pediatric patients. J Pediatr 2015;167(3):757-61.e1. PubMed
  8. Ghajar A, Gholamian F, Tabatabei-Motlagh M, et al. Citicoline (CDP-choline) add-on therapy to risperidone for treatment of negative symptoms in patients with stable schizophrenia: a double-blind, randomized placebo-controlled trial. Hum Psychopharmacol. 2
  9. Castagna A, Manzo C, Fabbo A, Lacava R, Ruberto C, Ruotolo G. The CITIMERIVA Study: CITIcoline plus MEmantina plus RIVAstigmine in Older Patients Affected with Alzheimer's Disease. Clin Drug Investig. 2021 Feb;41(2):177-182. PubMed
  10. Jeong H, Yoon S, Sung YH, et al. Effects of cytidine-5'-diphosphate choline on gray matter volumes in methamphetamine-dependent patients: A randomized, double-blind, placebo-controlled study. J Psychiatr Res 2021;143:215-221. PubMed
  11. Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F. Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Nutr 2021;151(8):2153-2160. PubMed

See these in context on the Citicoline monograph →

Ecklonia Cava 1 reference
  1. Lee DH, Park MY, Shim BJ, et al. Effects of Ecklonia cava polyphenol in individuals with hypercholesterolemia: a pilot study. J Med Food. 2012;15(11):1038-44.

See these in context on the Ecklonia Cava 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 →

Turmeric 102 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. Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 2001;7:1894-900..
  3. Shah BH, Nawaz Z, Pertani SA. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol 1 PubMed
  4. Hata M, Sasaki E, Ota M, et al . Allergic contact dermatitis from curcumin (turmeric). Contact Dermatitis 1997;36:107-8. PubMed
  5. Kuttan R, Sudheeran PC, Josph CD. Turmeric and curcumin as topical agents in cancer therapy. Tumori 1987;73:29-31.. PubMed
  6. Thapliyal R, Deshpande SS, Maru GB. Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts. Cancer Lett 2002;175:79-88. PubMed
  7. Lee SW, Nah SS, Byon JS, et al. Transient complete atrioventricular block associated with curcumin intake. Int J Cardiol 2011;150:e50-2. PubMed
  8. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, et al. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med 2009;15:891-7.
  9. Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011;4:354-64. PubMed
  10. Junyaprasert, V. B., Soonthornchareonnon, N., Thongpraditchote, S., Murakami, T., and Takano, M. Inhibitory effect of Thai plant extracts on P-glycoprotein mediated efflux. Phytother.Res 2006;20(1):79-81. PubMed
  11. Ampasavate, C., Sotanaphun, U., Phattanawasin, P., and Piyapolrungroj, N. Effects of Curcuma spp. on P-glycoprotein function. Phytomedicine. 2010;17(7):506-512. PubMed
  12. Hou, X. L., Takahashi, K., Tanaka, K., Tougou, K., Qiu, F., Komatsu, K., Takahashi, K., and Azuma, J. Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways. Int.J Pharm 6-24-2008;358(1-2):224-2 PubMed
  13. Choi, B. H., Kim, C. G., Lim, Y., Shin, S. Y., and Lee, Y. H. Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NF kappa B pathway. Cancer Lett. 1-18-2008;259(1):111-118.
  14. Zhang, W., Tan, T. M., and Lim, L. Y. Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab Dispos. 2007;35(1):110-115. PubMed
  15. Limtrakul, P., Chearwae, W., Shukla, S., Phisalphong, C., and Ambudkar, S. V. Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocu
  16. Holland, M. L., Panetta, J. A., Hoskins, J. M., Bebawy, M., Roufogalis, B. D., Allen, J. D., and Arnold, J. C. The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells. Biochem.Pharmacol 4-14-2006;71(8):1146-1154 PubMed
  17. Tang, X. Q., Bi, H., Feng, J. Q., and Cao, J. G. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. Acta Pharmacol Sin. 2005;26(8):1009-1016. PubMed
  18. Nabekura, T., Kamiyama, S., and Kitagawa, S. Effects of dietary chemopreventive phytochemicals on P-glycoprotein function. Biochem.Biophys.Res Commun. 2-18-2005;327(3):866-870. PubMed
  19. Romiti, N., Tongiani, R., Cervelli, F., and Chieli, E. Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes. Life Sci. 1998;62(25):2349-2358. PubMed
  20. Yue, G. G., Cheng, S. W., Yu, H., Xu, Z. S., Lee, J. K., Hon, P. M., Lee, M. Y., Kennelly, E. J., Deng, G., Yeung, S. K., Cassileth, B. R., Fung, K. P., Leung, P. C., and Lau, C. B. The role of turmerones on curcumin transportation and P-glycoprotein acti
  21. Shenouda, N. S., Zhou, C., Browning, J. D., Ansell, P. J., Sakla, M. S., Lubahn, D. B., and MacDonald, R. S. Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr.Cancer 2004;49(2):200-208. PubMed
  22. Appiah-Opong, R., Commandeur, J. N., Vugt-Lussenburg, B., and Vermeulen, N. P. Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products. Toxicology 6-3-2007;235(1-2):83-91. PubMed
  23. Hou, X. L., Takahashi, K., Kinoshita, N., Qiu, F., Tanaka, K., Komatsu, K., Takahashi, K., and Azuma, J. Possible inhibitory mechanism of Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated Caco-2 cells. Int.J Pharm 6-7-2007;337(1-2):169-177.
  24. Valentine, S. P., Le Nedelec, M. J., Menzies, A. R., Scandlyn, M. J., Goodin, M. G., and Rosengren, R. J. Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse. Life Sci. 4-11-2006;78(20):2391-2398. PubMed
  25. Price, R. J., Scott, M. P., Giddings, A. M., Walters, D. G., Stierum, R. H., Meredith, C., and Lake, B. G. Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes. Xenobiotica 2 PubMed
  26. Ganta, S., Devalapally, H., and Amiji, M. Curcumin enhances oral bioavailability and anti-tumor therapeutic efficacy of paclitaxel upon administration in nanoemulsion formulation. J Pharm Sci 2010;99(11):4630-4641. PubMed
  27. Lamb, S. R. and Wilkinson, S. M. Contact allergy to tetrahydrocurcumin. Contact Dermatitis 2003;48(4):227. PubMed
  28. Joshi, J., Ghaisas, S., Vaidya, A., Vaidya, R., Kamat, D. V., Bhagwat, A. N., and Bhide, S. Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers. J Assoc.Physicians India 2003;51:1055-1060.
  29. Mahesh, T., Balasubashini, M. S., and Menon, V. P. Effect of photo-irradiated curcumin treatment against oxidative stress in streptozotocin-induced diabetic rats. J Med.Food 2005;8(2):251-255. PubMed
  30. Thompson, D. A. and Tan, B. B. Tetrahydracurcumin-related allergic contact dermatitis. Contact Dermatitis 2006;55(4):254-255. PubMed
  31. Patumraj, S., Wongeakin, N., Sridulyakul, P., Jariyapongskul, A., Futrakul, N., and Bunnag, S. Combined effects of curcumin and vitamin C to protect endothelial dysfunction in the iris tissue of STZ-induced diabetic rats. Clin Hemorheol.Microcirc. 2006;3
  32. Liddle, M., Hull, C., Liu, C., and Powell, D. Contact urticaria from curcumin. Dermatitis 2006;17(4):196-197. PubMed
  33. Juan, H., Terhaag, B., Cong, Z., Bi-Kui, Z., Rong-Hua, Z., Feng, W., Fen-Li, S., Juan, S., Jing, T., and Wen-Xing, P. Unexpected effect of concomitantly administered curcumin on the pharmacokinetics of talinolol in healthy Chinese volunteers. Eur.J Clin PubMed
  34. Murugan, P. and Pari, L. Influence of tetrahydrocurcumin on erythrocyte membrane bound enzymes and antioxidant status in experimental type 2 diabetic rats. J Ethnopharmacol. 9-25-2007;113(3):479-486. PubMed
  35. Seo, K. I., Choi, M. S., Jung, U. J., Kim, H. J., Yeo, J., Jeon, S. M., and Lee, M. K. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol.Nutr.Food Res 2008;5
  36. Weisberg, S. P., Leibel, R., and Tortoriello, D. V. Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology 2008;149(7):3549-3558. PubMed
  37. Jain, S. K., Rains, J., Croad, J., Larson, B., and Jones, K. Curcumin supplementation lowers TNF-alpha, IL-6, IL-8, and MCP-1 secretion in high glucose-treated cultured monocytes and blood levels of TNF-alpha, IL-6, MCP-1, glucose, and glycosylated hemog
  38. Yu, Y., Hu, S. K., and Yan, H. [The study of insulin resistance and leptin resistance on the model of simplicity obesity rats by curcumin]. Zhonghua Yu Fang Yi.Xue.Za Zhi. 2008;42(11):818-822.
  39. Pavithra, B. H., Prakash, N., and Jayakumar, K. Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits. J Vet.Sci. 2009;10(4):293-297. PubMed
  40. Yan, Y. D., Kim, D. H., Sung, J. H., Yong, C. S., and Choi, H. G. Enhanced oral bioavailability of docetaxel in rats by four consecutive days of pre-treatment with curcumin. Int J Pharm 10-31-2010;399(1-2):116-120. PubMed
  41. Epelbaum, R., Schaffer, M., Vizel, B., Badmaev, V., and Bar-Sela, G. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 2010;62(8):1137-1141. PubMed
  42. Madkor, H. R., Mansour, S. W., and Ramadan, G. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats. Br J Nutr 2011;105(8):1210-1217. PubMed
  43. Pungcharoenkul, K. and Thongnopnua, P. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects. Phytother Res 2011;25(11):1721-1726.
  44. Kusuhara, H., Furuie, H., Inano, A., Sunagawa, A., Yamada, S., Wu, C., Fukizawa, S., Morimoto, N., Ieiri, I., Morishita, M., Sumita, K., Mayahara, H., Fujita, T., Maeda, K., and Sugiyama, Y. Pharmacokinetic interaction study of sulphasalazine in healthy
  45. Mohammadi, A., Sahebkar, A., Iranshahi, M., Amini, M., Khojasteh, R., Ghayour-Mobarhan, M., and Ferns, G. A. Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. Phytother Res 2013;27(3):374-379. PubMed
  46. Chuengsamarn, S., Rattanamongkolgul, S., Luechapudiporn, R., Phisalaphong, C., and Jirawatnotai, S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012;35(11):2121-2127. PubMed
  47. Goh, C. L. and Ng, S. K. Allergic contact dermatitis to Curcuma longa (turmeric). Contact Dermatitis 1987;17(3):186. PubMed
  48. Srivastava, R., Puri, V., Srimal, R. C., and Dhawan, B. N. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelforschung. 1986;36(4):715-717.
  49. Srinivasan, M. Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 1972;26(4):269-270.
  50. Srivastava, K. C., Bordia, A., and Verma, S. K. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot.Essent.Fatty Acids 1995;52(4):223-227 PubMed
  51. Oetari, S., Sudibyo, M., Commandeur, J. N., Samhoedi, R., and Vermeulen, N. P. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver. Biochem Pharmacol 1-12-1996;51(1):39-45. PubMed
  52. Kiec-Swierczynska, M. and Krecisz, B. Occupational allergic contact dermatitis due to curcumin food colour in a pasta factory worker. Contact Dermatitis 1998;39(1):30-31. PubMed
  53. Van Dau N, Ngoc Ham N, Huy Khac D, and et al. The effects of a traditional drug, tumeric (Curcuma longa), and placebo on the healing of duodenal ulcer. Phytomed 1998;5(1):29-34.
  54. Daveluy A, Géniaux H, Thibaud L, Mallaret M, Miremont-Salamé G, Haramburu F. Probable interaction between an oral vitamin K antagonist and turmeric (Curcuma longa). Therapie. 2014 Nov-Dec;69(6):519-20. PubMed
  55. Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, Buntragulpoontawee M, Lukkanapichonchut P, Chootip C, Saengsuwan J, Tantayakom K, Laongpech S. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthrit
  56. Madhu K, Chanda K, Saji MJ. Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: a randomized placebo-controlled trial. Inflammopharmacology 2013;21(2):129-36. PubMed
  57. Mali AM, Behal R, Gilda SS. Comparative evaluation of 0.1% turmeric mouthwash with 0.2% chlorhexidine gluconate in prevention of plaque and gingivitis: A clinical and microbiological study. J Indian Soc Periodontol 2012;16(3):386-91. PubMed
  58. Sanmukhani J, Satodia V, Trivedi J, Patel T, Tiwari D, Panchal B, Goel A, Tripathi CB. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res 2014;28(4):579-85. PubMed
  59. Nayeri A, Wu S, Adams E, et al. Acute Calcineurin Inhibitor Nephrotoxicity Secondary to Turmeric Intake: A Case Report. Transplant Proc. 2017;49(1):198-200. PubMed
  60. Mitchell TM. Correspondence re: Somasundaram et al., Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2003;63(16):5165-6; author reply 5166-7.
  61. Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2002;62(13):3868-75.
  62. Haroyan A, Mukuchyan V, Mkrtchyan N, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;18(1):7. PubMed
  63. Al-Karawi D, Al Mamoori DA, Tayyar Y. The role of curcumin administration in patients with major depressive disorder: Mini meta-analysis of clinical trials. Phytother Res. 2016;30(2):175-83. PubMed
  64. Neerati P, Devde R, Gangi AK. Evaluation of the effect of curcumin capsules on glyburide therapy in patients with type-2 diabetes mellitus. Phytother Res. 2014;28(12):1796-800. PubMed
  65. Simental-Mendía LE, Pirro M, Gotto AM Jr, et al. Lipid-modifying activity of curcuminoids: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2017:1-10. PubMed
  66. Fung FY, Wong WH, Ang SK, et al. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017;32:88-96. PubMed
  67. Small GW, Siddarth P, Li Z, et al. Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: A double-blind, placebo-controlled 18-month trial. Am J Geriatr Psychiatry. 2018;26(3):266-277.
  68. Cruz-Correa M, Hylind LM, Marrero JH, et al. Efficacy and safety of curcumin in treatment of intestinal adenomas in patients with familial adenomatous polyposis. Gastroenterology. 2018 May 23. Pii:S0016-5085(18)34564-5. [Epub ahead of print] PubMed
  69. Rahmani S, Asgary S, Askari G, et al. Treatment of non-alcoholic fatty liver disease with curcumin: a randomized placebo-controlled trial. Phytother Res. 2016 Sep;30(9):1540-8. PubMed
  70. Lopez-Villafuerte L, CLores KH. Contact dermatitis caused by turmeric in a massage oil. Contact Dermatitis. 2016 Jul;75(1):52-3. PubMed
  71. Lukefahr AL, McEvoy S, Alfafara C, Funk JL. Drug-induced autoimmune hepatitis associated with turmeric dietary supplement use. BMJ Case Rep. 2018. pii: bcr-2018-224611. PubMed
  72. Medsafe Safety Communication- Turmeric/Curcumin Interaction with Warfarin. April 30, 2018. Accessed at: https://medsafe.govt.nz/safety/EWS/2018/Turmeric.asp.
  73. Imam Z, Khasawneh M, Jomaa D, Iftikhar H, Sayedahmad Z. Drug induced liver injury attributed to a curcumin supplement. Case Rep Gastrointest Med 2019 Oct 20;2019:6029403. doi: 10.1155/2019/6029403. PubMed
  74. Chand S, Hair C, Beswick L. A rare case of turmeric-induced hepatotoxicity. Intern Med J. 2020;50(2):258-259. PubMed
  75. Jiang N, Zhang M, Meng X, Sun B. Effects of Curcumin on the Pharmacokinetics of Amlodipine in Rats and Its Potential Mechanism. Pharm Biol. 2020;58(1):465-468. PubMed
  76. Lee BS, Bhatia T, Chaya CT, Wen R, Taira MT, Lim BS. Autoimmune Hepatitis Associated With Turmeric Consumption. ACG Case Rep J. 2020;7(3):e00320. PubMed
  77. Lombardi N, Crescioli G, Maggini V, et al. Acute liver injury following turmeric use in Tuscany: an analysis of the Italian Phytovigilance database and systematic review of case reports. Br J Clin Pharmacol. 2020. PubMed
  78. Suhail FK, Masood U, Sharma A, John S, Dhamoon A. Turmeric supplement induced hepatotoxicity: a rare complication of a poorly regulated substance. Clin Toxicol (Phila). 2020;58(3):216-217. PubMed
  79. Nakagawa Y, Mukai S, Yamada S, et al. The efficacy and safety of highly-bioavailable curcumin for treating knee osteoarthritis: a 6-month open-labeled prospective study. Clin Med Insights Arthritis Musculoskelet Disord. 2020;13:1179544120948471. PubMed
  80. Shafabakhsh R, Asemi Z, Reiner Z, Soleimani A, Aghadavod E, Bahmani F. The effects of nano-curcumin on metabolic status in patients with diabetes on hemodialysis, a randomized, double blind, placebo-controlled trial. Iran J Kidney Dis. 2020;14(4):290-9.
  81. Allegri P, Rosa R, Masala A, et al. Clinical effectiveness of a new oral curcumin formulation in acute non-infectious uveitic macular edema: a 12-month observational study. Eur Rev Med Pharmacol Sci 2022;26(1):46-53.
  82. Tsai IC, Hsu CW, Chang CH, Tseng PT, Chang KV. The effect of curcumin differs on individual cognitive domains across different patient populations: A systematic review and meta-analysis. Pharmaceuticals (Basel) 2021;14(12):1235. PubMed
  83. Alam MA, Bin Jardan YA, Raish M, Al-Mohizea AM, Ahad A, Al-Jenoobi FI. Herb-drug interaction: Pharmacokinetics and pharmacodynamics of anti-hypertensive drug amlodipine besylate in presence of lepidium sativum and curcuma longa. Xenobiotica 2022;1-9.
  84. Sohal A, Alhankawi D, Sandhu S, Chintanaboina J. Turmeric-induced hepatotoxicity: Report of 2 cases. Int Med Case Rep J 2021;14:849-852. PubMed
  85. Hussaarts KGAM, Hurkmans DP, Oomen-de Hoop E, et al. Impact of curcumin (with or without piperine) on the pharmacokinetics of tamoxifen. Cancers (Basel). 2019;11(3):403. PubMed
  86. Kalluru H, Mallayasamy SR, Kondaveeti SS, Chandrasekhar V, Kalachaveedu M. Effect of turmeric supplementation on the pharmacokinetics of paclitaxel in breast cancer patients: A study with population pharmacokinetics approach. Phytother Res 2022;36(4):1761 PubMed
  87. 109288 Halegoua-DeMarzio D, Navarro V, Ahmad J, et al. Liver injury associated with turmeric-A growing problem: Ten cases from the drug-induced liver injury network [DILIN]. Am J Med. 2022:S0002-9343(22)00740-9. PubMed
  88. Arzallus T, Izagirre A, Castiella A, Torrente S, Garmendia M, Zapata EM. Drug induced autoimmune hepatitis after turmeric intake. Gastroenterol Hepatol 2023. PubMed
  89. Gilad O, Rosner G, Ivancovsky-Wajcman D, et al. Efficacy of wholistic turmeric supplement on adenomatous polyps in patients with familial adenomatous polyposis-A randomized, double-blinded, placebo-controlled study. Genes (Basel) 2022;13(12):2182. PubMed
  90. Ahad A, Raish M, Abdelrahman IA, et al. Changes in pharmacokinetics and pharmacodynamics of losartan in experimental diseased rats treated with Curcuma longa and Lepidium sativum. Pharmaceuticals (Basel) 2022;16(1):33. PubMed
  91. 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
  92. 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
  93. Kou H, Huang L, Jin M, He Q, Zhang R, Ma J. Effect of curcumin on rheumatoid arthritis: a systematic review and meta-analysis. Front Immunol 2023;14:1121655. PubMed
  94. Qiu L, Gao C, Wang H, et al. Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials. Front PubMed
  95. Sato T, Yagi A, Yamauchi M, et al. The use of an antioxidant enables accurate evaluation of the interaction of curcumin on organic anion-transporting polypeptides 4C1 by preventing auto-oxidation. Int J Mol Sci 2024;25(2):991. PubMed
  96. Washington O, Robinson E, Simh D, et al. Oxalate nephropathy and chronic turmeric supplementation: a case report. J Bras Nefrol 2024;46(1):99-106. PubMed
  97. Munshi R, Karande-Patil S, Kumbhar D, Deshmukh A, Hingorani L. A randomized, controlled, comparative, proof-of-concept study to evaluate the efficacy and safety of Nisha-Amalaki capsules in prediabetic patients for preventing progression to diabetes. J Ay PubMed
  98. Sharifi Razavi A, Mohajerani F, Niksolat F, Karimi N. Efficacy of topical curcumin on mild to moderate carpal tunnel syndrome: a randomized double-blind, placebo-controlled clinical trial. Pain Med 2024;25(5):327-333. PubMed
  99. Yaikwawong M, Jansarikit L, Jirawatnotai S, Chuengsamarn S. Curcumin Reduces Depression in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial. Nutrients 2024;16(15):2414. PubMed
  100. Tehrani SD, Hosseini A, Shahzamani M, et al. Evaluation of the effectiveness of curcumin and piperine co-supplementation on inflammatory factors, cardiac biomarkers, atrial fibrillation, and clinical outcomes after coronary artery bypass graft surgery. Cl PubMed
  101. Yaikwawong M, Jansarikit L, Jirawatnotai S, Chuengsamarn S. The Effect of Curcumin on Reducing Atherogenic Risks in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial. Nutrients 2024;16(15):2441. PubMed
  102. Dibaei M, Hosseini A, Lavasani H, Kiani-Dehkordi B, Rouini M. Assessment of metabolic interaction between curcumin and tramadol using the isolated perfused rat liver. Heliyon 2024;10(15):e35070. PubMed

See these in context on the Turmeric monograph →

Alpha-gpc 4 references
  1. Di Perri R, Coppola G, Ambrosio LA, et al. A multicentre trial to the evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. J Int Med Res 1991;19:330-41.
  2. Barbagallo Sangiorgi G, Barbagallo M, Giordano M, et al. Alpha-glycerophosphocholine in the mental recovery of cerebral ischemic attacks: An Italian multicenter clinical trial. Ann N Y Acad Sci 1994;717:253-69. PubMed
  3. Canal N, Franceschi M, Alberoni M, et al. Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine. Int J Clin Pharmacol Ther Toxicol 1991;29:103-7.
  4. Lee G, Choi S, Chang J, et al. Association of L-a glycerylphosphorylcholine with subsequent stroke risk after 10 Years. JAMA Netw Open 2021;4(11):e2136008.

See these in context on the Alpha-gpc 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