Major interaction on record — check this product against your medications before combining. Based on 19 of 23 ingredients. Check your meds →
Dietary supplement

RejuvaCel Ingredients & Drug Interactions

by FirstFitness Nutrition

Other (e.g. Tea Bag) Category: Other Combinations
Most serious interaction: Major
The interaction bottom line Most serious interaction: Major

RejuvaCel is a dietary supplement by FirstFitness Nutrition with 23 active ingredients. Its ingredients are commonly taken for hair, skin, and nail health, bone health and osteoporosis, joint and connective tissue support.Based on those ingredients, 1,671 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Tea extracts, Curcumin, Grape extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of RejuvaCel by FirstFitness Nutrition

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

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

Most active ingredients don't disclose an individual amount — you can't tell how much of each you're getting.

Why this rating?
  • The label discloses an exact amount for 6 of its 23 active ingredients.
  • “Glucosanol Complex” is a proprietary blend — the label gives one combined amount (1,418.50 mg) without saying how much of each component you get.
  • “Active Herbal Complex” is a proprietary blend — the label gives one combined amount (300 mg) without saying how much of each component you get.
  • “2 AEP Complex” is a proprietary blend — the label gives one combined amount (100 mg) without saying how much of each component you get.

RejuvaCel contains 23 ingredients, of which the active ones include silica, aspartic acid, magnesium, vitamin C, copper, grape extract, vitamin E, manganese, DHEA (dehydroepiandrosterone), vitamin A, glucosamine salt, gotu kola extract, curcumin, zinc, shark cartilage concentrate, green tea extract, wild yam extract, and butcher's broom extract. The product also contains several inactive ingredients—dicalcium phosphate, hydrogenated cottonseed oil, croscarmellose sodium, and magnesium stearate—which serve as binders, fillers, and flow agents.

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: joint protection and connective tissue support.
  • We looked for evidence on: Aging, Aging skin, Joint pain, Mobility, Flexibility.
  • The strongest evidence on file: Dhea is rated "Possibly Effective" for Aging skin (Natural Medicines).
  • Also on file: Vitamin A is rated "Possibly Effective" for Aging skin.
  • Also on file: Dhea is rated "Possibly Ineffective" for Aging.

Evidence on effectiveness is mixed and often limited. Silica is possibly effective for bone health (osteoporosis), though evidence on hair loss is insufficient.

Magnesium is effective for digestive upset and constipation, and possibly effective for blood pressure. Vitamin C is effective for vitamin C deficiency and possibly effective for anemia and infections after heavy exercise.

Glucosamine is likely effective for osteoarthritis. Green tea extract is likely effective for human papillomavirus (HPV) and possibly effective for cholesterol.

Curcumin (from turmeric) is possibly effective for depression, cholesterol, and allergies. Most other ingredients have insufficient evidence or are possibly ineffective for their claimed uses—including grape extract, gotu kola, shark cartilage, and wild yam for their respective indications.

The overall evidence base for this multi-ingredient formula as a whole is not established in the data we hold.

The evidence, ingredient by ingredient Silicon Vitamin C Copper Vitamin E Manganese Dhea Vitamin A Zinc

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 18 of the 19 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 19 of 19.
  • General safety write-ups exist for 19 of 19.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated at normal doses. Magnesium commonly causes diarrhea, nausea, and gastrointestinal upset, especially at higher doses.

Vitamin C can cause abdominal cramps, diarrhea, nausea, and heartburn above 2 grams daily. Green tea extract has been linked to rare liver injury in concentrated, high-dose forms.

Curcumin typically causes constipation or diarrhea, nausea, and dyspepsia. Zinc can cause metallic taste, nausea, vomiting, and diarrhea, particularly at doses above 40 mg daily.

DHEA may cause acne, headache, insomnia, mood changes, and—in women—male-pattern symptoms like voice deepening and excess hair growth. For pregnancy: silica, aspartic acid, vitamin A (especially at high doses), and DHEA should be avoided; magnesium is needed but use only under doctor guidance; vitamin C, copper, and manganese are generally acceptable at dietary amounts but avoid high-dose supplements without medical advice; green tea, gotu kola, shark cartilage, and wild yam lack sufficient safety data and are best avoided.

For breastfeeding: avoid silica, aspartic acid, DHEA, and gotu kola; use caution with high-dose manganese, vitamin E, and curcumin; green tea and wild yam safety is unknown; magnesium, vitamin C, copper, glucosamine, and zinc at normal dietary amounts are generally acceptable but check with your healthcare provider.

Side effects, ingredient by ingredient Silicon Vitamin C Copper Vitamin E Manganese Dhea Vitamin A Zinc

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?
  • 17 of the 19 matched ingredients can interact with medications — Manganese, Butcher's Broom, Dhea, Grape, Turmeric, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,672 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 RejuvaCel, check with your doctor or pharmacist about these medication types: blood thinners and antiplatelet drugs (warfarin, anticoagulants), because vitamin E, grape extract, and DHEA may increase bleeding risk; blood pressure medications, especially nadolol and calcium channel blockers, because green tea and magnesium can reduce effectiveness or cause drops in pressure; cholesterol drugs like atorvastatin, because green tea reduces their levels; Parkinson's medications (levodopa/carbidopa), because magnesium cuts absorption; thyroid medication (levothyroxine), because vitamin C may increase absorption; antibiotics including quinolones, tetracyclines, and cephalosporins, because magnesium and zinc reduce their absorption; chemotherapy drugs, because vitamin C, vitamin E, and curcumin have antioxidant effects that may interfere; diabetes drugs, because magnesium may increase their effects; and hormone therapies or oral contraceptives, because vitamin C and wild yam may alter estrogen or interfere with cancer treatments like tamoxifen and aromatase inhibitors. No interactions are documented for the few ingredients we could not check.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with some supporting evidence for its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

RejuvaCel is a complex multi-ingredient formula with limited overall evidence of benefit and significant interaction potential, especially with blood pressure, cholesterol, blood-thinning, and seizure medications, as well as chemotherapy and hormone therapies. If you take any prescription medications—particularly for heart, blood pressure, thyroid, diabetes, seizures, or cancer—talk with your doctor or pharmacist before starting this product.

Women who are pregnant or breastfeeding should discuss it with their healthcare provider, as several ingredients carry safety concerns in these states.

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

Assessment coverage: 19 of 23 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Dec 26, 2020.

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 RejuvaCel, straight from the product label.

Brand FirstFitness Nutrition
Net contents 60 Caplet(s)
Market status On market
Date entered into DSLD Dec 26, 2020
DSLD ID 239655
Product type Other Combinations
Supplement form Other (e.g. Tea Bag)
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
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 RejuvaCel by FirstFitness Nutrition, 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:
2 Caplet(s)
Maximum serving Sizes:
2 Caplet(s)
Servings per container
30
IngredientAmount% DV
Silica0 NP--
Aspartic Acid0 NP--
Magnesium0 NP--
Vitamin C60 mg100%
Copper2 mg100%
Grape extract0 NP--
Vitamin E30 IU100%
Manganese10 mg500%
Dehydroepiandrosterone0 NP--
Vitamin A1000 IU20%
Glucosamine Salt0 NP--
Orotic Acid0 NP--
2-Aminoethanol Phosphate0 NP--
Gotu Kola extract0 NP--
Curcumin0 NP--
Zinc15 mg100%
Glucosanol Complex1418.5 mg--
Shark Cartilage concentrate0 NP--
Chondroitin Mucopolysaccharides0 NP--
Green Tea extracts0 NP--
Pine extract0 NP--
Active Herbal Complex300 mg--
Wild Yam extract0 NP--
Butcher's Broom extract0 NP--
2 AEP Complex100 mg--
Calcium 2-Aminoethanol Phosphate0 NP--

Other ingredients: Dicalcium Phosphate, hydrogenated Cottonseed oil, Croscarmellose Sodium, Magnesium Stearate

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.
Formulation

Maximum joint protection

The results: With regular use, RejuvaCel can help alleviate daily discomfort associated with joint pain, injury and/or connective tissue damage. Assists with flexibility and mobility. By helping to alleviate joint pain, a person can resume most normal activities with little or no discomfort.

Added antioxidant power helps improve quality of skin, hair and nails.

Improved quality of life as you are able to resume daily activities. Helps to tighten up loose and sagging skin.

Helps support and protect joints Assists with joint mobility and flexibility Helps with pain relief following strenuous exercise Helps tighten loose skin

Formula

The solution: RejuvaCel is the nutritional formulation to protect and support healthy joints and supply vital nutrients to skin and connective tissues. With ingredients such as glucosamine sulfate, chondroitin mucopolysaccharides and shark cartilage, antioxidants like vitamin A, C and E, also play a large part in why RejuvaCel helps ease joint pain. Not only does RejuvaCel assist with joint difficulties, it also helps support development of connective tissues and helps improve quality of skin, hair, and nails.

2 caplets of RejuvaCel contain 50 mg of OPC's (Oligomeric Proanthocyanadins) from pine bark and grape seed extracts.

Suggested/Recommended/Usage/Directions

Directions: For the first three months, take 2-3 caplets once daily. Thereafter, take 1 tablet per day for maintenance. RejuvaCel is best when taken with food. For greater results, follow the RejuvaCel Health & Skin care program: Avoid overexposure to the sun, drink plenty of water, use a good moisturizer, follow a good diet, reduce stress, and get plenty of exercise.

Directions: Take 2 caplets once daily with food.

FDA Disclaimer Statement

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

General Statements

Health & wellness

Item #1615

FDA Statement of Identity

Dietary Supplement

Brand IP Statement(s)

OptiZinc brand. Optizinc is a registered trademark of Interhealth. Pycnogenol brand. Pycnogenol is a registered trademark of Horphag Research LTD.

See for yourself

RejuvaCel by FirstFitness Nutrition label

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

What’s inside

The Ingredients in RejuvaCel by FirstFitness Nutrition

These are the 23 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Caplet(s) Dosage formOther (e.g. Tea Bag) Servings per container30 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.

Silica

No known
interactions
0 NP per serving

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 h...

Silica monograph & interactions

Vitamin C

Interacts with
207 drugs
60 mg per serving Form: Ascorbic Acid

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 im...

Vitamin C monograph & interactions

Copper

Interacts with
31 drugs
2 mg per serving Form: Copper Sulfate

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

Copper monograph & interactions

Vitamin E

Interacts with
764 drugs
30 IU per serving Form: D-Alpha-Tocopherol Acetate

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

Vitamin E monograph & interactions

Manganese

Interacts with
83 drugs
10 mg per serving Form: Manganese Sulfate

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

Manganese monograph & interactions

Dehydroepiandrosterone

Interacts with
776 drugs
0 NP per serving

DHEA is a natural hormone that the body makes and that declines with age, and it is sold as a supplement claiming many benefits. The evidence is mixed...

Dehydroepiandrosterone monograph & interactions

Vitamin A

Interacts with
387 drugs
1000 IU per serving Form: Vitamin A Palmitate

Vitamin A is an essential nutrient important for vision, skin, immune function, and growth. Most people get enough from a balanced diet, and supplemen...

Vitamin A monograph & interactions

Zinc

Interacts with
67 drugs
15 mg per serving Form: Zinc Monomethionine

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

Zinc monograph & interactions

Glucosanol Complex

1418.5 mg per serving

Active Herbal Complex

300 mg per serving

2 AEP Complex

100 mg per serving

Other (inactive) ingredients: Dicalcium Phosphate, Hydrogenated Cottonseed oil, Croscarmellose Sodium, Magnesium Stearate. These complete the product’s ingredient list but are not active constituents.

Interaction report

RejuvaCel by FirstFitness Nutrition Drug Interactions

Want to check YOUR meds against RejuvaCel?

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
1,671Drugs
37 Major 1,617 Moderate 17 Minor

Ingredients driving the most interactions

Curcumin 1,133
Vitamin E 764

Each ingredient & the kinds of drugs it affects

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

Green Tea extracts58 drug types · 1,293 drugs

Atorvastatin (Lipitor)

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

Likelihood Likely Evidence B
Ephedrine

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

Likelihood Probable Evidence D
Nadolol (Corgard)

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

Likelihood Likely Evidence B
5-Fluorouracil

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

Likelihood Possible Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

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

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

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

Likelihood Probable Evidence D
Bortezomib (Velcade)

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

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

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

Likelihood Possible Evidence D
Celiprolol (Celicard)

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

Likelihood Possible Evidence D
Cimetidine (Tagamet)

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

Likelihood Likely Evidence B
Clozapine (Clozaril)

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

Likelihood Possible Evidence B
Contraceptive Drugs

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

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

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

Likelihood Possible Evidence D
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

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

Likelihood Possible Evidence D
Felbamate (Felbatol)

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

Likelihood Possible Evidence D
Fexofenadine (Allegra)

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

Likelihood Probable Evidence B
Flutamide (Eulexin)

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

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Hepatotoxic Drugs

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

Likelihood Unlikely Evidence D
Imatinib (Gleevec)

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

Likelihood Possible Evidence D

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

Grape extract9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

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

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

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

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

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

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

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

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

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

Likelihood Possible Evidence D
Midazolam (Versed)

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

Likelihood Possible Evidence D
Phenacetin

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

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

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

Likelihood Unlikely Evidence D

Dehydroepiandrosterone10 drug types · 776 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, DHEA might increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Human and laboratory research show that DHEA and DHEA-S can inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidepressant Drugs

Theoretically, DHEA might increase the risk of psychiatric adverse events when used with antidepressants.
In a human case report, the use of a selective serotonin reuptake inhibitor (SSRI) with DHEA caused a manic episode. Concern for this interaction may be greater in younger individuals with higher baseline DHEA levels.

Likelihood Possible Evidence D
Aromatase Inhibitors

Theoretically, DHEA might interfere with the clinical effects of aromatase inhibitors.
DHEA is a potent estrogen agonist, which may antagonize the anti-estrogen activity of aromatase inhibitors.

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

Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.
Some preliminary evidence shows that DHEA may inhibit CYP3A4; however, the clinical significance of this potential interaction is not known.

Likelihood Possible Evidence D
Fulvestrant (Faslodex)

Theoretically, DHEA might interfere with the anti-estrogen effects of fulvestrant.
DHEA is a potent estrogen agonist. Some research shows that it can overcome the estrogen receptor antagonist action of fulvestrant in estrogen-receptor positive cancer cells.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, DHEA might interfere with the anti-estrogen effects of tamoxifen.
DHEA is a potent estrogen agonist. Some research shows that it can overcome the estrogen receptor antagonist activity of tamoxifen in estrogen-receptor positive cancer cells.

Likelihood Possible Evidence D
Triazolam (Halcion)

DHEA can increase blood levels of triazolam.
Administration of DHEA 200 mg daily for two weeks was shown to inhibit the cytochrome P450 3A4 (CYP3A4) metabolism of triazolam. This inhibition appears to be due to DHEA-S, rather than DHEA.

Likelihood Probable Evidence D
Tuberculosis Vaccine

DHEA might reduce the effectiveness of the tuberculosis vaccine.
Animal research shows that high doses of DHEA can reduce the efficacy of the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine.

Likelihood Possible Evidence D
Estrogens

Theoretically, DHEA might increase the effects and adverse effects of estrogen therapy.
DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones. Also, in clinical research, estrogen-progestin oral contraceptives and conjugated estrogens reduce blood levels of DHEA and DHEA-S. The clinical significance of these findings is unclear.

Likelihood Possible Evidence D
Testosterone

Theoretically, DHEA might increase the effects and side effects of testosterone therapy.
DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones. The clinical significance of these findings is unclear.

Likelihood Possible Evidence D

Vitamin E8 drug types · 764 drugs

Alkylating Agents

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

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence B
Antitumor Antibiotics

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

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

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

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

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

Likelihood Possible Evidence D
Selumetinib (Koselugo)

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

Likelihood Possible Evidence D
Warfarin (Coumadin)

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

Likelihood Possible Evidence B
Niacin

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

Likelihood Possible Evidence A

Gotu Kola extract2 drug types · 579 drugs

Cns Depressants

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

Likelihood Possible Evidence D
Hepatotoxic Drugs

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

Likelihood Possible Evidence D

Vitamin A4 drug types · 387 drugs

Retinoids

Concomitant use of retinoids with vitamin A supplements might produce supratherapeutic vitamin A levels.
Retinoids, which are vitamin A derivatives, could have additive toxic effects when taken with vitamin A supplements.

Likelihood Probable Evidence D
Hepatotoxic Drugs

Theoretically, taking high doses of vitamin A in combination with other potentially hepatotoxic drugs might increase the risk of liver disease.
The tolerable upper intake level (UL) is the highest level of intake that is likely to pose no risk of adverse effects. Doses of vitamin A above the UL can cause hepatotoxicity, ranging from elevated liver enzymes to liver failure.

Likelihood Possible Evidence C
Tetracycline Antibiotics

Theoretically, taking tetracycline antibiotics with high doses of vitamin A can increase the risk of pseudotumor cerebri.
Benign intracranial hypertension (pseudotumor cerebri) can occur with tetracyclines and with acute or chronic vitamin A toxicity. Case reports suggest that taking tetracyclines and vitamin A concurrently can increase the risk of this condition. Avoid high doses of vitamin A in people taking tetracyclines chronically.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, high doses of vitamin A could increase the risk of bleeding with warfarin.
Vitamin A toxicity is associated with hemorrhage and hypoprothrombinemia, possibly due to vitamin K antagonism. Advise patients taking warfarin to avoid doses of vitamin A above the tolerable upper intake level of 10,000 IU/day for adults.

Likelihood Possible Evidence D

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

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

Glucosamine Salt4 drug types · 170 drugs

Warfarin (Coumadin)

Glucosamine might increase the anticoagulant effects of warfarin and increase the risk of bruising and bleeding.
In two individual case reports, glucosamine/chondroitin combinations were associated with a significant increase in international normalized ratio (INR) in patients previously stabilized on warfarin. In one case, the increase in INR occurred only after tripling the dose of a glucosamine/chondroitin supplement from 500 mg/400 mg daily to 1500/1200 mg daily. Additionally, 20 voluntary case reports to the U.S. Food & Drug Administration (FDA) have linked glucosamine plus chondroitin with increased INR, bruising, and bleeding in patients who were also taking warfarin. There have also been 20 additional case reports to the World Health Organization (WHO) that link glucosamine alone to increased INR in patients taking warfarin. The mechanism of this interaction is unclear. Glucosamine is a small component of heparin, but is not thought to have anticoagulant activity; however, animal research suggests that it might have antiplatelet activity.

Likelihood Probable Evidence D
Topoisomerase Ii Inhibitors

Theoretically glucosamine may induce resistance to topoisomerase II inhibitors.
In vitro research suggests that glucosamine might induce resistance to etoposide (VP16, VePesid) and doxorubicin (Adriamycin) by reducing inhibition of topoisomerase II, an enzyme required for DNA replication in tumor cells. This effect has not been reported in humans.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

Acetaminophen might interfere with the activity of glucosamine sulfate by interacting with the sulfate portion.
Anecdotal reports suggest that adding glucosamine to an acetaminophen regimen might decrease pain control in patients with osteoarthritis. Some research suggests that the sulfate portion of glucosamine sulfate might contribute to its effect in osteoarthritis. Since acetaminophen metabolism requires sulfur and reduces serum sulfate concentrations, acetaminophen could theoretically interfere with the action of glucosamine sulfate. Conversely, the administration of sulfate could theoretically decrease the effectiveness of acetaminophen in sulfate-deficient people by increasing its clearance.

Likelihood Possible Evidence B
Antidiabetes Drugs

Despite initial concerns, it is unlikely that glucosamine will interfere with the effects of antidiabetes drugs.
In vitro and animal research has suggested that glucosamine might increase insulin resistance or decrease insulin production. This has raised concerns that taking glucosamine might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that glucosamine does not have adverse effects on blood glucose or glycated hemoglobin (HbA1C) in healthy, obese, or type 2 diabetes patients.

Likelihood Unlikely Evidence B

Calcium 2-Aminoethanol Phosphate18 drug types · 168 drugs

Ceftriaxone (Rocephin)

Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction. So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.

Likelihood Probable Evidence D
Dolutegravir (Tivicay)

Calcium seems to reduce levels of dolutegravir.
Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation.

Likelihood Probable Evidence B
Elvitegravir (Vitekta)

Calcium seems to reduce levels of elvitegravir.
Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation.

Likelihood Probable Evidence B
Aluminum

Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease. However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption.

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

Calcium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption when taken in a fasting state.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide and calcium can be taken together if taken with food. However, if taken on an empty stomach, bictegravir/emtricitabine/tenofovir alafenamide should not be taken with, or 2 hours after, calcium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Calcium reduces the absorption of bisphosphonates.
Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates.

Likelihood Probable Evidence C
Calcipotriene (Dovonex)

Taking calcipotriene with calcium might increase 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 calcium supplements might increase the risk of hypercalcemia.

Likelihood Possible Evidence B
Digoxin (Lanoxin)

Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. However, one retrospective analysis of clinical data suggests that intravenous calcium does not increase the risk of dysrhythmias or mortality in patients receiving digoxin.

Likelihood Possible Evidence B
Diltiazem (Cardizem, Others)

Theoretically, calcium may reduce the therapeutic effects of diltiazem.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.

Likelihood Probable Evidence D
Levothyroxine (Synthroid, Others)

Calcium seems to reduce the absorption and effectiveness of levothyroxine.
Advise patients to take levothyroxine and calcium supplements at least 4 hours apart. Calcium reduces levothyroxine absorption, probably by forming insoluble complexes. Calcium carbonate supplements reduce effectiveness of levothyroxine in patients with hypothyroidism.

Likelihood Probable Evidence B
Lithium

Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients. Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.

Likelihood Possible Evidence B
Quinolone Antibiotics

Calcium seems to reduce the absorption of quinolone antibiotics.
Advise patients to take oral quinolones at least 2 hours before or 4-6 hours after calcium supplements or calcium-fortified foods. Taking calcium at the same time as oral quinolones can reduce quinolone absorption. Calcium binds to quinolones in the gut.

Likelihood Probable Evidence B
Raltegravir (Isentress)

Calcium may reduce levels of raltegravir.
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir. However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure.

Likelihood Possible Evidence B
Sotalol (Betapace)

Calcium seems to reduce the absorption of sotalol.
Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes.

Likelihood Possible Evidence B
Tetracycline Antibiotics

Calcium seems to reduce the absorption of tetracycline antibiotics.
Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut.

Likelihood Probable Evidence C
Thiazide Diuretics

Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
Thiazides reduce calcium excretion by the kidneys. Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.

Likelihood Probable Evidence C
Verapamil (Calan, Others)

Theoretically, calcium may reduce the therapeutic effects of verapamil.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.

Likelihood Probable Evidence D
Calcium Channel Blockers

Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects. But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers.

Likelihood Unlikely Evidence D

Butcher's Broom extract2 drug types · 158 drugs

Alpha-Adrenergic Agonists

Theoretically, butcher's broom might increase the effects and adverse effects of alpha-adrenergic agonists.
Animal and in vitro studies show that butcher's broom has alpha-adrenergic agonist effects.

Likelihood Possible Evidence D
Alpha-Adrenergic Antagonists

Theoretically, butcher's broom might reduce the effects of alpha-adrenergic antagonists.
Animal and in vitro studies show that butcher's broom has alpha-adrenergic agonist effects.

Likelihood Possible Evidence D

Shark Cartilage concentrate1 drug type · 121 drugs

Immunosuppressants

Theoretically, shark cartilage might interfere with immunosuppressive therapy.
In vitro evidence suggests that shark cartilage might stimulate immune responses. This effect has not been reported in humans.

Likelihood Possible Evidence D

Manganese3 drug types · 83 drugs

Antipsychotic Drugs

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence D
Tetracycline Antibiotics

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

Likelihood Probable Evidence D

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

Wild Yam extract1 drug type · 41 drugs

Estrogens

Theoretically, wild yam might increase or decrease the effects of estrogen.
Wild yam root shows estrogenic and anti-estrogenic effects in vitro. Theoretically, wild yam might interfere with hormone therapy.

Likelihood Possible Evidence D

Copper2 drug types · 31 drugs

Penicillamine (Cuprimine, Depen)

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

Likelihood Probable Evidence D
Contraceptive Drugs

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

Likelihood Possible Evidence D
The maker

Brand information

Manufacturer and brand details for RejuvaCel, from the product label.

FirstFitness Nutrition

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FirstFitness Nutrition
Pharmacist Counseling Corner

RejuvaCel by FirstFitness Nutrition: Common Questions

Does RejuvaCel by FirstFitness Nutrition interact with any medications?
Yes. Based on its ingredients, RejuvaCel has a known interaction with 1,671 medications, including 37 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
RejuvaCel contains 23 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.
Is RejuvaCel safe to take if I'm pregnant?
No—several ingredients should be avoided or used cautiously in pregnancy. Silica, aspartic acid, vitamin A (especially high doses), and DHEA should not be used. Magnesium is needed in pregnancy but only under your doctor's guidance. Talk with your doctor or pharmacist before taking this product if you are pregnant or planning to become pregnant.
Can I take RejuvaCel while breastfeeding?
Safety varies by ingredient. Avoid silica, aspartic acid, DHEA, and gotu kola; use caution with high-dose manganese, vitamin E, and curcumin; green tea and wild yam safety is unknown. Magnesium, vitamin C, copper, glucosamine, and zinc at normal dietary amounts are generally acceptable. Check with your doctor or pharmacist before starting, as your baby will be exposed through breast milk.
Does RejuvaCel actually work for joint health and skin?
Glucosamine is likely effective for osteoarthritis, and several ingredients are possibly effective for various conditions—curcumin for inflammation, vitamin C for skin health, silica for bone strength. However, evidence for many others (grape extract, gotu kola, shark cartilage, wild yam) is limited or shows them possibly ineffective for their claimed uses. The overall benefit of the formula as a whole is not established.
What are the most common side effects of RejuvaCel?
Magnesium commonly causes diarrhea, nausea, and stomach upset. Vitamin C may cause cramps and diarrhea at higher doses. Zinc can cause metallic taste, nausea, and vomiting. Curcumin may cause constipation or diarrhea and nausea. DHEA in women may cause acne and unwanted hair growth. Most other ingredients are well tolerated, but side effects depend on individual sensitivity and dose.
Can I take RejuvaCel with my blood pressure or cholesterol medication?
It depends on your specific medication. Green tea extract in RejuvaCel can significantly reduce the effectiveness of nadolol and atorvastatin. Magnesium may have additive blood-pressure-lowering effects with calcium channel blockers. Use your doctor or pharmacist to check your exact medications against the interactions listed on this page before starting.
Does RejuvaCel contain any ingredients we couldn't check for interactions?
Yes, we could not check the interaction data for orotic acid, 2-aminoethanol phosphate, chondroitin mucopolysaccharides, and pine extract because we hold no monograph or data for them. If you take medications and want to be thorough, ask your pharmacist about these four ingredients specifically.

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

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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.

RejuvaCel label
Go deeper

The Full Monographs Behind RejuvaCel’s Ingredients

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

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 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

Copper

Interacts with 31 drugs

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

Read the full Copper monograph →
Herb & supplement monograph

Vitamin E

Interacts with 764 drugs

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

Read the full Vitamin E monograph →
Herb & supplement monograph

Manganese

Interacts with 83 drugs

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

Read the full Manganese monograph →
Herb & supplement monograph

Dhea

Interacts with 776 drugs

DHEA is a natural hormone that the body makes and that declines with age, and it is sold as a supplement claiming many benefits. The evidence is mixed and limited for most uses, and because...

Read the full Dhea monograph →
Herb & supplement monograph

Vitamin A

Interacts with 387 drugs

Vitamin A is an essential nutrient important for vision, skin, immune function, and growth. Most people get enough from a balanced diet, and supplements are mainly useful for correcting a tr...

Read the full Vitamin A 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

Grape

Interacts with 910 drugs

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

Read the full Grape monograph →
Herb & supplement monograph

Glucosamine

Interacts with 170 drugs

Glucosamine is a natural compound found in cartilage and joint fluid, and it is one of the most popular supplements for osteoarthritis, especially of the knee. The evidence is mixed, with so...

Read the full Glucosamine 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

Shark Cartilage

Interacts with 121 drugs

Shark cartilage is a supplement made from the skeletal tissue of sharks that was heavily promoted for cancer and joint conditions, but good-quality clinical trials have not shown meaningful...

Read the full Shark Cartilage monograph →
Herb & supplement monograph

Green Tea

Interacts with 1,293 drugs

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

Read the full Green Tea monograph →
Herb & supplement monograph

Gotu Kola

Interacts with 579 drugs

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

Read the full Gotu Kola monograph →
Herb & supplement monograph

Wild Yam

Interacts with 41 drugs

Wild yam is a root traditionally used for menopausal symptoms, cramps, and as a so-called 'natural' hormone supplement, but solid human evidence for these uses is lacking. Despite popular cl...

Read the full Wild Yam monograph →
Herb & supplement monograph

Butcher's Broom

Interacts with 158 drugs

Butcher's broom is a plant extract most often used for circulation problems in the legs, such as chronic venous insufficiency, where some evidence suggests it may help reduce swelling and di...

Read the full Butcher's Broom monograph →
Herb & supplement monograph

Aspartic Acid

Aspartic acid is a common amino acid your body makes on its own and gets from protein-rich foods, so a true deficiency is rare. D-aspartic acid is heavily marketed for boosting testosterone...

Read the full Aspartic Acid 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

Calcium

Interacts with 168 drugs

Calcium is an essential mineral your body needs for strong bones, nerve signaling, and muscle function, and supplements can help fill gaps when diet falls short. Most people do best getting...

Read the full Calcium monograph →
Sources

Sources & How We Checked

RejuvaCel'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 986 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.

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

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Aspartic Acid 1 reference
  1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press, 2005. Available at: https://doi.org/10.17226 DOI

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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.

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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 →

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

See these in context on the Copper monograph →

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

See these in context on the Grape monograph →

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

See these in context on the Vitamin E monograph →

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

See these in context on the Manganese monograph →

Dhea 98 references
  1. Frye RF, Kroboth PD, Folan MM, et al. Effect of DHEA on CYP3A-mediated metabolism of triazolam. Clin Pharmacol Ther 2000;67:109 (abstract PI-82).
  2. Kuritzky L. DHEA: Science or wishful thinking? Hosp Pract 1998;33:85-6. PubMed
  3. Van Vollenhoven RF, Morabito LM, Engleman EG, et al. Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol 1998;25:285-9.
  4. Van Vollenhoven RF, Engleman EG, McGurie JL. Dehydroepiandrosterone in Systemic Lupus Erythematosus. Arth Rheum 1995;38:1826-31. DOI
  5. Ebeling P, Koivisto VA. Physiological importance of dehydroepiandrosterone. Lancet 1994;343:1479-81. PubMed
  6. Yen SS, Morales AJ, Khorram O. Replacement of DHEA in aging men and women. Potential remedial effects. Ann N Y Acad Sci 1995;774:128-42. PubMed
  7. Labrie F, Diamond P, Cusan L, et al. Effect of 12 month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab 1997;82:3498-505. PubMed
  8. Casson PR, Faquin LC, Stentz FB. Replacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in postmenopausal women. (abstract) Fertil Steril 1995;63:1027-31. DOI
  9. Morales AJ, Haubrich RH, Hwang JY, et al. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf)1 PubMed
  10. Arlt W, Justl H, Callies F, et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. [Abstract] J Clin Endocrinol PubMed
  11. Kline MD, Jaggers ED. Mania onset while using dehydroepiandrosterone (letter). Am J Psychiatry 1999;156:971. PubMed
  12. Callies F, Arlt W, Siekmann L, et al. Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females. Steroids 2000;65:98-102. PubMed
  13. Markowitz JS, Carson WH, Jackson CW. Possible dihydroepiandrosterone-induced mania. Biol Psychiatry 1999;45:241-2. PubMed
  14. Stoll BA. Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk. Eur J Clin Nutr 1999;53:771-5. PubMed
  15. Dean CE. Prasterone (DHEA) and mania. Ann Pharmacother 2000;34:1419-22. PubMed
  16. Himmel PB, Seligman TM. A Pilot Study Employing Dehydroepiandrosterone (DHEA) in the Treatment of Chronic Fatigue Syndrome. [Abstract]. J Clin Rheumatol 1999:5:56-9. PubMed
  17. Hunt PJ, Gurnell EM, Huppert FA, et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. J Clin Endocrinol Metab 2000;85:4650-6.. PubMed
  18. Johannsson G, Burman P, Wiren L, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002;87:2046-52. PubMed
  19. Calhoun KE, Pommier RF, Muller P, et al. Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant. Arch Surg 2003;138:879-83.. PubMed
  20. Morris KT, Toth-Fejel S, Schmidt J, et al. High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy. Surgery PubMed
  21. Calhoun K, Pommier R, Cheek J, et al. The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression. Am J Surg 2003;185:411-5.. PubMed
  22. Stomati M, Monteleone P, Casarosa E, et al. Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol Endocrinol 2000;14:342-63.. PubMed
  23. Petri MA, Mease PJ, Merrill JT, et al. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis Rheum 2004;50:2858-68. PubMed
  24. Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf) 2000;53:561-8. PubMed
  25. Acacio BD, Stanczyk FZ, Mullin P, et al. Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men. Fertil Steril 2004;81:595-604. PubMed
  26. Petri MA, Lahita RG, Van Vollenhoven RF, et al. Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2002;46:1820-9. PubMed
  27. Pino JA, Marbot R. Volatile flavor constituents of acerola (Malpighia emarginata DC.) fruit. J Agric Food Chem 2001;49:5880-2.
  28. Nair KS, Rizza RA, O'Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 2006;355:1647-59. PubMed
  29. Alkatib AA, Cosma M, Elamin MB, et al. A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab 2009;94:3676-81. PubMed
  30. Jesse, R. L., Loesser, K., Eich, D. M., Qian, Y. Z., Hess, M. L., Nestler, J. E. Dehydroepiandrosterone inhibits human platelet aggregation in vitro and in vivo. Ann N.Y.Acad Sci 1995;774:281-90.
  31. Bertoni, A., Rastoldo, A., Sarasso, C., Di Vito C., Sampietro, S., Nalin, M., Bagarotti, A., Sinigaglia, F. Dehydroepiandrosterone-sulfate inhibits thrombin-induced platelet aggregation. Steroids 2012;77(3):260-8. PubMed
  32. Cui, Y., Choi, I. S., Koh, Y. A., Lin, X. H., Cho, Y. B., Won, Y. H. Effects of combined BCG and DHEA treatment in preventing the development of asthma. Immunol Invest 2008;37(3):191-202. PubMed
  33. Aisaka, K., Mori, H., Ogawa, T., Kigawa, T. Effects of dehydroepiandrosterone-sulphate (DHEA-S) administration on puerperal lactation and maternal prolactin and estradiol levels. Nippon Sanka Fujinka Gakkai Zasshi 1984;36(10):1935-42.
  34. Lauritzen, C. [Therapeutic attempts with dehydroepiandrosterone sulfate in threatened pregnancies]. Arch Gynakol 1971;211(1):247-9.
  35. Mortola, J. F. Yen, S. S. The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. J Clin Endocrinol Metab 1990;71(3):696-704. PubMed
  36. Rabijewski, M., Zgliczynski, W. [Positive effects of DHEA therapy on insulin resistance and lipids in men with angiographically verified coronary heart disease--preliminary study]. Endokrynol Pol 2005;56(6):904-10.
  37. Weiss, E. P., Shah, K., Fontana, L., Lambert, C. P., Holloszy, J. O., Villareal, D. T. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am J Clin Nutr 2009;89(5):1459-67. PubMed
  38. Jankowski, C. M., Gozansky, W. S., Kittelson, J. M., Van Pelt, R. E., Schwartz, R. S., Kohrt, W. M. Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens. J Clin E PubMed
  39. Poretsky, L., Song, L., Brillon, D. J., Ferrando, S., Chiu, J., McElhiney, M., Ferenczi, A., Sison, C., Haller, I., Rabkin, J. Metabolic and hormonal effects of oral DHEA in premenopausal women with HIV infection: a randomized, prospective, placebo-contro
  40. Libe, R., Barbetta, L., Dall'Asta, C., Salvaggio, F., Gala, C., Beck-Peccoz, P., Ambrosi, B. Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism. J Endocrinol Invest 2004;27 PubMed
  41. Genazzani, A. R., Inglese, S., Lombardi, I., Pieri, M., Bernardi, F., Genazzani, A. D., Rovati, L., Luisi, M. Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. Aging Male 2004;7(2):133-43. PubMed
  42. von Muhlen D., Laughlin, G. A., Kritz-Silverstein, D., Bergstrom, J., Bettencourt, R. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int 2008;19(5):
  43. Kritz-Silverstein, D., von, Muhlen D., Laughlin, G. A., Bettencourt, R. Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: the DHEA and Well-Ness (DAWN) Trial. J Am Geriatr Soc 2008;56(7):1292-8. PubMed
  44. Penisson-Besnier, I., Devillers, M., Porcher, R., Orlikowski, D., Doppler, V., Desnuelle, C., Ferrer, X., Bes, M. C., Bouhour, F., Tranchant, C., Lagrange, E., Vershueren, A., Uzenot, D., Cintas, P., Sole, G., Hogrel, J. Y., Laforet, P., Vial, C., Vila, A
  45. Casson, P. R., Santoro, N., Elkind-Hirsch, K., Carson, S. A., Hornsby, P. J., Abraham, G., Buster, J. E. Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high-density lipoprotein: a six-month t
  46. Araneo, B. Daynes, R. Dehydroepiandrosterone functions as more than an antiglucocorticoid in preserving immunocompetence after thermal injury. Endocrinology 1995;136(2):393-401. PubMed
  47. Nordmark, G., Bengtsson, C., Larsson, A., Karlsson, F. A., Sturfelt, G., Ronnblom, L. Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus. Autoimmunity PubMed
  48. Srinivasan, M., Irving, B. A., Frye, R. L., O'Brien, P., Hartman, S. J., McConnell, J. P., Nair, K. S. Effects on lipoprotein particles of long-term dehydroepiandrosterone in elderly men and women and testosterone in elderly men. J Clin Endocrinol Metab 2 PubMed
  49. Srinivasan, M., Irving, B. A., Dhatariya, K., Klaus, K. A., Hartman, S. J., McConnell, J. P., Nair, K. S. Effect of dehydroepiandrosterone replacement on lipoprotein profile in hypoadrenal women. J Clin Endocrinol Metab 2009;94(3):761-4. PubMed
  50. Jankowski, C. M., Gozansky, W. S., Van Pelt, R. E., Wolfe, P., Schwartz, R. S., Kohrt, W. M. Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids. Clin Endocrinol (Oxf) 2011;75(4):456-6 PubMed
  51. McHenry, C. M., Bell, P. M., Hunter, S. J., Thompson, C. J., Courtney, C. H., Ennis, C. N., Sheridan, B., McCance, D. R., Mullan, K. R., Atkinson, A. B. Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life i
  52. Jankowski, C. M., Gozansky, W. S., Schwartz, R. S., Dahl, D. J., Kittelson, J. M., Scott, S. M., Van Pelt, R. E., Kohrt, W. M. Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial. J PubMed
  53. Forsblad-d'Elia, H., Carlsten, H., Labrie, F., Konttinen, Y. T., Ohlsson, C. Low serum levels of sex steroids are associated with disease characteristics in primary Sjogren's syndrome; supplementation with dehydroepiandrosterone restores the concentration
  54. Finckh, A., Berner, I. C., Aubry-Rozier, B., So, A. K. A randomized controlled trial of dehydroepiandrosterone in postmenopausal women with fibromyalgia. J Rheumatol 2005;32(7):1336-40.
  55. Gebre-Medhin, G., Husebye, E. S., Mallmin, H., Helstrom, L., Berne, C., Karlsson, F. A., Kampe, O. Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease. Clin Endocrinol (Oxf) 2000;52(6):775-80. PubMed
  56. Lovas, K., Gebre-Medhin, G., Trovik, T. S., Fougner, K. J., Uhlving, S., Nedrebo, B. G., Myking, O. L., Kampe, O., Husebye, E. S. Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month,
  57. Pillemer, S. R., Brennan, M. T., Sankar, V., Leakan, R. A., Smith, J. A., Grisius, M., Ligier, S., Radfar, L., Kok, M. R., Kingman, A., Fox, P. C. Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjogren's syndrome. Arthritis Rheum
  58. Christiansen, J. J., Andersen, N. H., Sorensen, K. E., Pedersen, E. M., Bennett, P., Andersen, M., Christiansen, J. S., Jorgensen, J. O., Gravholt, C. H. Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and
  59. Panjari, M., Bell, R. J., Jane, F., Wolfe, R., Adams, J., Morrow, C., Davis, S. R. A randomized trial of oral DHEA treatment for sexual function, well-being, and menopausal symptoms in postmenopausal women with low libido. J Sex Med 2009;6(9):2579-90. PubMed
  60. Mamas, L., Mamas, E. Dehydroepiandrosterone supplementation in assisted reproduction: rationale and results. Curr Opin Obstet Gynecol 2009;21(4):306-8. PubMed
  61. Hartkamp, A., Geenen, R., Godaert, G. L., Bootsma, H., Kruize, A. A., Bijlsma, J. W., Derksen, R. H. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren syndrome: a randomised controlled tr
  62. Yeung, T. W., Li, R. H., Lee, V. C., Ho, P. C., Ng, E. H. A randomized double-blinded placebo-controlled trial on the effect of dehydroepiandrosterone for 16 weeks on ovarian response markers in women with primary ovarian insufficiency. J Clin Endocrinol PubMed
  63. Virkki, L. M., Porola, P., Forsblad-d'Elia, H., Valtysdottir, S., Solovieva, S. A., Konttinen, Y. T. Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjogren's syndrome. Arthritis Care Res (Ho
  64. Binder, G., Weber, S., Ehrismann, M., Zaiser, N., Meisner, C., Ranke, M. B., Maier, L., Wudy, S. A., Hartmann, M. F., Heinrich, U., Bettendorf, M., Doerr, H. G., Pfaeffle, R. W., Keller, E. Effects of dehydroepiandrosterone therapy on pubic hair growth an
  65. Klove, K. L., Roy, S., Lobo, R. A. The effect of different contraceptive treatments on the serum concentration of dehydroepiandrosterone sulfate. Contraception 1984;29(4):319-24. PubMed
  66. Cibula, D., Fanta, M., Vrbikova, J., Stanicka, S., Dvorakova, K., Hill, M., Skrha, J., Zivny, J., Skrenkova, J. The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogena
  67. White, T., Jain, J. K., Stanczyk, F. Z. Effect of oral versus transdermal steroidal contraceptives on androgenic markers. Am J Obstet Gynecol 2005;192(6):2055-9. PubMed
  68. Vacheron-Trystram, M. N., Cheref, S., Gauillard, J., Plas, J. [A case report of mania precipitated by use of DHEA]. Encephale 2002;28(6 Pt 1):563-6.
  69. Gurnell, E. M., Hunt, P. J., Curran, S. E., Conway, C. L., Pullenayegum, E. M., Huppert, F. A., Compston, J. E., Herbert, J., Chatterjee, V. K. Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial. J Clin Endocrinol PubMed
  70. Christiansen, J. J., Bruun, J. M., Christiansen, J. S., Jorgensen, J. O., Gravholt, C. H. Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial. Eur J Endocrinol 2011;165(2 PubMed
  71. Bloch, M., Ish-Shalom, S., Greenman, Y., Klein, E., Latzer, Y. Dehydroepiandrosterone treatment effects on weight, bone density, bone metabolism and mood in women suffering from anorexia nervosa-a pilot study. Psychiatry Res 2012;200(2-3):544-9. PubMed
  72. Merritt, P., Stangl, B., Hirshman, E., Verbalis, J. Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women. Brain Res 11-5-2012;1483:54-62. PubMed
  73. Stangl, B., Hirshman, E., and Verbalis, J. Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial performance in postmenopausal women. Behav Neurosci 2011;125(5):742-52. PubMed
  74. Artini, P. G., Simi, G., Ruggiero, M., Pinelli, S., Di Berardino, O. M., Papini, F., Papini, S., Monteleone, P., Cela, V. DHEA supplementation improves follicular microenviroment in poor responder patients. Gynecol Endocrinol 2012;28(9):669-73. PubMed
  75. Genazzani, A. R., Stomati, M., Valentino, V., Pluchino, N., Pot, E., Casarosa, E., Merlini, S., Giannini, A., Luisi, M. Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality. Climacteric 2011;14(6):661-8. PubMed
  76. Dayal, M., Sammel, M. D., Zhao, J., Hummel, A. C., Vandenbourne, K., Barnhart, K. T. Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids. J Womens Health (Larchmt) 2005;14(5):391-400. PubMed
  77. Vogiatzi, M. G., Boeck, M. A., Vlachopapadopoulou, E., el-Rashid, R., New, M. I. Dehydroepiandrosterone in morbidly obese adolescents: effects on weight, body composition, lipids, and insulin resistance. Metabolism 1996;45(8):1011-5. PubMed
  78. Bernardi, F., Pieri, M., Stomati, M., Luisi, S., Palumbo, M., Pluchino, N., Ceccarelli, C., Genazzani, A. R. Effect of different hormonal replacement therapies on circulating allopregnanolone and dehydroepiandrosterone levels in postmenopausal women. Gyne DOI
  79. Schlegel, W., Petersdorf, L. I., Junker, R., Schulte, H., Ebert, C., Von Eckardstein, A. The effects of six months of treatment with a low-dose of conjugated oestrogens in menopausal women. Clin Endocrinol (Oxf) 1999;51(5):643-51. PubMed
  80. Rao, M. S., Subbarao, V., Yeldandi, A. V., and Reddy, J. K. Hepatocarcinogenicity of dehydroepiandrosterone in the rat. Cancer Res. 5-15-1992;52(10):2977-2979.
  81. Tagliaferro, A. R., Roebuck, B. D., Ronan, A. M., and Meeker, L. D. Enhancement of pancreatic carcinogenesis by dehydroepiandrosterone. Adv.Exp.Med Biol. 1992;322:119-129. PubMed
  82. Buster, J. E., Casson, P. R., Straughn, A. B., Dale, D., Umstot, E. S., Chiamori, N., and Abraham, G. E. Postmenopausal steroid replacement with micronized dehydroepiandrosterone: preliminary oral bioavailability and dose proportionality studies. Am J Ob
  83. Kocis, P. Prasterone. Am J Health Syst.Pharm. 11-15-2006;63(22):2201-2210.
  84. Karp, G., Bentov, Y., Masalha, R., and Ifergane, G. Onset of late posttraumatic seizure after dehydroepiandrosterone treatment. Fertil.Steril. 2009;91(3):931-932. PubMed
  85. Stanczyk, F. Z., Slater, C. C., Ramos, D. E., Azen, C., Cherala, G., Hakala, C., Abraham, G., and Roy, S. Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term oral dehydroepiandrosterone treatment in postmenopausal women. Menopa PubMed
  86. Rice, S. P., Agarwal, N., Bolusani, H., Newcombe, R., Scanlon, M. F., Ludgate, M., and Rees, D. A. Effects of dehydroepiandrosterone replacement on vascular function in primary and secondary adrenal insufficiency: a randomized crossover trial. J Clin End PubMed
  87. Mizokami, A., Koh, E., Izumi, K., Narimoto, K., Takeda, M., Honma, S., Dai, J., Keller, E. T., and Namiki, M. Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of testosterone and dihydrotestoster
  88. Liu, X., Arnold, J. T., and Blackman, M. R. Dehydroepiandrosterone administration or G{alpha}q overexpression induces {beta}-catenin/T-Cell factor signaling and growth via increasing association of estrogen receptor-{beta}/Dishevelled2 in androgen-indepe
  89. El-Alfy, M., Deloche, C., Azzi, L., Bernard, B. A., Bernerd, F., Coutet, J., Chaussade, V., Martel, C., Leclaire, J., and Labrie, F. Skin responses to topical dehydroepiandrosterone: implications in antiageing treatment? Br.J Dermatol. 2010;163(5):968-97 PubMed
  90. Chen, M. J., Chen, C. D., Yang, J. H., Chen, C. L., Ho, H. N., Yang, W. S., and Yang, Y. S. High serum dehydroepiandrosterone sulfate is associated with phenotypic acne and a reduced risk of abdominal obesity in women with polycystic ovary syndrome. Hum. PubMed
  91. Goldberg, M. Dehydroepiandrosterone, insulin-like growth factor-I, and prostate cancer. Ann Intern Med 10-1-1998;129(7):587-588. PubMed
  92. Sahelian, R. and Borken, S. Dehydroepiandrosterone and cardiac arrhythmia. Ann Intern.Med 10-1-1998;129(7):588. PubMed
  93. Liao YH, Liao KF, Kao CL, et al. Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage. Eur J Appl Physiol 2013;113(1):99-107. PubMed
  94. Yeung TW, Chai J, Li RH, et al. A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders. Fertil Steril 2014;102(1):108-115.e1. PubMed
  95. Buisson C, Frelat C, Privat K, Martinat N, Audran M, Collomp K. Metabolic and isotopic signature of short-term DHEA administration in women: Comparison with findings in men. Drug Test Anal. 2018;10(11-12):1744-1754. PubMed
  96. Gravisse N, Vibarel-Rebot N, Labsy Z, et al. Short-term dehydroepiandrosterone intake and supramaximal exercise in young recreationally-trained women. Int J Sports Med. 2018;39(9):712-719. PubMed
  97. Chen SN, Tsui KH, Wang PH, Chern CU, Wen ZH, Lin LT. Dehydroepiandrosterone supplementation improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve. Front Endocrinol (Lausanne). 2019;10:800. PubMed
  98. Li Y, Ren J, Li N, et al. A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials. Exp Gerontol 2020;141:111110. Online ahead of print. PubMed

See these in context on the Dhea monograph →

Vitamin A 31 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Griffiths JK. The vitamin A paradox. J Pediatr 2000;137:604-7.. PubMed
  3. Hardman JG, Limbird LL, Molinoff PB, eds. Goodman and Gillman's The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw-Hill, 1996.
  4. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  5. FDA Talk Paper. Vitamin A and birth defects (T95-56). Food and Drug Administration, U.S. Department of Health and Human Services, Rockville, MD. October 6, 1995.
  6. Russell RM. The vitamin A spectrum: from deficiency to toxicity. Am J Clin Nutr 2000;71:878-84. PubMed
  7. 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.
  8. Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002;287:47-54. PubMed
  9. Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 1998;129:770-8. PubMed
  10. Michaelsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med 2003;348:287-94.. PubMed
  11. Botterweck AA, van den Brandt PA, Goldbohm RA. Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma: results from a prospective study after 6.3 years of follow-up. Cancer 2000;88:737-48.. DOI
  12. Meyskens FL Jr, Graham V, Chvapil M, et al. A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia. J Natl Cancer Inst 1983;71:921-5..
  13. Hathcock JN, Hattan DG, Jenkins MY, et al. Evaluation of vitamin A toxicity. Am J Clin Nutr 1990;52:183-202.. PubMed
  14. Walters BN, Gubbay SS. Tetracycline and benign intracranial hypertension: report of five cases. Br Med J 1981;282:19-20.. PubMed
  15. Pearson MG, Littlewood SM, Bowden AN. Tetracycline and benign intracranial hypertension (letter). Br Med J 1981;282:568-9.. PubMed
  16. Azais-Braesco V, Pascal G. Vitamin A in pregnancy: requirements and safety limits. Am J Clin Nutr 2000;71:1325S-33S. PubMed
  17. Smedts HP, de Vries JH, Rakhshandehroo M, et al. High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring. BJOG 2009;116:416-23. PubMed
  18. Grotto, I., Mimouni, M., Gdalevich, M., and Mimouni, D. Vitamin A supplementation and childhood morbidity from diarrhea and respiratory infections: a meta-analysis. J Pediatr 2003;142(3):297-304. PubMed
  19. Mahalanabis, D., Lahiri, M., Paul, D., Gupta, S., Gupta, A., Wahed, M. A., and Khaled, M. A. Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc or vitamin A in infants and young children with severe acute l
  20. Long, K. Z., Montoya, Y., Hertzmark, E., Santos, J. I., and Rosado, J. L. A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mex
  21. Fritz, H., Kennedy, D., Fergusson, D., Fernandes, R., Doucette, S., Cooley, K., Seely, A., Sagar, S., Wong, R., and Seely, D. Vitamin A and retinoid derivatives for lung cancer: a systematic review and meta analysis. PLoS.One. 2011;6(6):e21107. PubMed
  22. Mayo-Wilson, E., Imdad, A., Herzer, K., Yakoob, M. Y., and Bhutta, Z. A. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. BMJ 2011;343:d5094. PubMed
  23. Mazumder S, Taneja S, Bhatia K, Yoshida S, Kaur J, Dube B, Toteja GS, Bahl R, Fontaine O, Martines J, Bhandari N; Neovita India Study Group. Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovit
  24. Baineni R, Gulati R, Delhi CK. Vitamin A toxicity presenting as bone pain. Arch Dis Child. 2017;102(6):556-8. PubMed
  25. Darlow BA, Graham PJ, Rojas-Reyes MX. Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2016;(8):CD000501. PubMed
  26. Haider BA, Sharma R, Bhutta ZA. Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in low and middle income countries. Cochrane Database Syst Rev. 2017;2:CD006980. PubMed
  27. Mohammad YM, Raslan IR, Al-Hussain FA. Idiopathic Intracranial Hypertension Induced by Topical Application of Vitamin A. J Neuroophthalmol. 2016;36(4):412-3. PubMed
  28. Masnadi Shirazi K, Nikniaz Z, Masnadi Shirazi A, Rohani M. Vitamin A supplementation decreases disease activity index in patients with ulcerative colitis: A randomized controlled clinical trial. Complement Ther Med. 2018 Dec;41:215-219. PubMed
  29. Ding Y, Hu P, Yang Y, et al. Impact of maternal daily oral low-dose vitamin A supplementation on the mother-infant pair: a randomised placebo-controlled trial in China. Nutrients 2021;13(7):2370. PubMed
  30. Knapik JJ, Hoedebecke SS. Vitamin A and bone fractures: systematic review and meta-analysis. J Spec Oper Med 2021;21(2):100-7. PubMed
  31. Imdad A, Mayo-Wilson E, Haykal MR, et al. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database Syst Rev 2022;3(3):CD008524. PubMed

See these in context on the Vitamin A monograph →

Glucosamine 58 references
  1. Adams ME. Hype about glucosamine. Lancet 1999;354:353-4. PubMed
  2. Balkan B, Dunning BE. Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats. Diabetes 1994;43:1173-9. PubMed
  3. Giaccari A, Morviducci L, Zorretta D, et al. In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia. Diabetologia 1995;38:518-24. PubMed
  4. Holmang A, Nilsson C, Niklasson M, et al. Induction of insulin resistance by glucosamine reduces blood flow but not interstitial levels of either glucose or insulin. Diabetes 1999;48:106-11. PubMed
  5. Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26:2423-30.
  6. Barclay TS, Tsourounis C, McCart GM. Glucosamine. Ann Pharmacother 1998;32:574-9.
  7. Shankar RR, Zhu JS, Baron AD. Glucosamine infusion in rats mimics the beta-cell dysfunction of non-insulin-dependent diabetes mellitus. Metabolism 1998;47:573-7.
  8. Almada A, Harvey P, Platt K. Effects of chronic oral glucosamine sulfate on fasting insulin resistance index (FIRI) in non-diabetic individuals. FASEB J 2000;14:A750.
  9. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomised, placebo-controlled trial. Lancet 2001;357:251-6.
  10. Does glucosamine increase serum lipid levels and blood pressure? Pharmacist's Letter/Prescriber's Letter 2001;17(11):171115.
  11. 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.
  12. Monauni T, Zenti MG, Cretti A, et al. Effects of glucosamine infusion on insulin secretion and insulin action in humans. Diabetes 2000;49:926-35. PubMed
  13. Pouwels MJ, Jacobs JR, Span PN, et al. Short-term glucosamine infusion does not affect insulin sensitivity in humans. J Clin Endocrinol Metab 2001;86:2099-103. DOI
  14. Yun J, Tomida A, Nagata K, Tsuruo T. Glucose-regulated stresses confer resistance to VP-16 in human cancer cells through a decreased expression of DNA topoisomerase II. Oncol Res 1995;7:583-90.
  15. Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: A 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162:2113-23. PubMed
  16. Tallia AF, Cardone DA. Asthma exacerbation associated with glucosamine-chondroitin supplement. J Am Board Fam Pract 2002;15:481-4..
  17. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med 2003; PubMed
  18. Hoffer LJ, Kaplan LN, Hamadeh MJ, et al. Sulfate could mediate the therapeutic effect of glucosamine sulfate. Metabolism 2001;50:767-70.. PubMed
  19. Yu JG, Boies SM, Olefsky JM. The effect of oral glucosamine sulfate on insulin sensitivity in human subjects. Diabetes Care 2003;26:1941-2. PubMed
  20. Danao-Camara T. Potential side effects of treatment with glucosamine and chondroitin. Arthritis Rheum 2000;43:2853. PubMed
  21. Guillaume MP, Peretz A. Possible association between glucosamine treatment and renal toxicity: comment on the letter by Danao-Camara. Arthritis Rheum 2001;44:2943-4. PubMed
  22. Rozenfeld V, Crain JL, Callahan AK. Possible augmentation of warfarin effect by glucosamine-chondroitin. Am J Health Syst Pharm 2004;61:306-307. PubMed
  23. Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilage 2004;12:506-11. PubMed
  24. Bush TM, Rayburn KS, Holloway SW, et al. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey. Altern Ther Health Med 2007;13:30-5.
  25. Stumpf JL, Lin SW. Effect of glucosamine on glucose control. Ann Pharmacother 2006;40:694-8. PubMed
  26. Pham T, Cornea A, Blick KE, et al. Oral glucosamine in doses used to treat osteoarthritis worsens insulin resistance. Am J Med Sci 2007;333:333-9. PubMed
  27. Muniyappa R, Karne RJ, Hall G, et al. Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects. Diabetes 2006;55:3142-50. PubMed
  28. Knudsen J, Sokol GH. Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: Case report and review of the literature and MedWatch database. Pharmacotherapy 2008;28:540-8. PubMed
  29. Yue QY, Strandell J, Myrberg O. Concomitant use of glucosamine potentiates the effect of warfarin. Jan 2006. Drug Safety 29(10):911-1010. DOI
  30. Rozendaal RM, Koes BW, van Osch GJVM, et al. Effect of glucosamine sulfate on hip osteoarthritis: A randomized trial. Ann Intern Med 2008;148:268-77. PubMed
  31. Baron AD, Zhu JS, Zhu JH, et al. Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity. J Clin Invest 1995;96(6):2792-801. PubMed
  32. Nelson BA, Robinson KA, Buse MG. High glucose and glucosamine induce insulin resistance via different mechanisms in 3T3-L1 adipocytes. Diabetes 2000;49(6):981-91. PubMed
  33. Giordano N, Fioravanti A, Papakostas P, et al. The efficacy and tolerability of glucosamine sulfate in the treatment of knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Curr Ther Res Clin Exp 2009;70(3):185-196. PubMed
  34. Shaygannejad, V., Janghorbani, M., Savoj, M. R., and Ashtari, F. Effects of adjunct glucosamine sulfate on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized, placebo-controlled trial. Neurol Res 2010;32(9):981-985. PubMed
  35. Cahlin, B. J. and Dahlstrom, L. No effect of glucosamine sulfate on osteoarthritis in the temporomandibular joints--a randomized, controlled, short-term study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112(6):760-766. PubMed
  36. Cerda C, Bruguera M, Parés A. Hepatotoxicity associated with glucosamine and chondroitin sulfate in patients with chronic liver disease. World J Gastroenterol 2013;19(32):5381-4. PubMed
  37. Hochberg MC, Martel-Pelletier J, Monfort J, Möller I, Castillo JR, Arden N,Berenbaum F, Blanco FJ, Conaghan PG, Doménech G, Henrotin Y, Pap T, Richette P, Sawitzke A, du Souich P, Pelletier JP; on behalf of the MOVES Investigation Group. Combined chondroi
  38. von Felden J, Montani M, Kessebohm K, Stickel F. Drug-induced acute liver injury mimicking autoimmune hepatitis after intake of dietary supplements containing glucosamine and chondroitin sulfate. Int J Clin Pharmacol Ther 2013;51(3):219-23. PubMed
  39. Provenza JR, Shinjo SK, Silva JM, Peron CR, Rocha FA. Combined glucosamine and chondroitin sulfate, once or three times daily, provides clinically relevant analgesia in knee osteoarthritis. Clin Rheumatol 2015;34:1455-62. PubMed
  40. Ossendza RA, Grandval P, Chinoune F, Rocher F, Chapel F, Bernardini D. [Acute cholestatic hepatitis due to glucosamine forte]. Gastroenterol Clin Biol. 2007 Apr;31(4):449-50.
  41. Audimoolam VK, Bhandari S. Acute interstitial nephritis induced by glucosamine. Nephrol Dial Transplant 2006;21(7):2031. PubMed
  42. Greenlee H, Crew KD, Shao T, Kranwinkel G, Kalinsky K, Maurer M, Brafman L, Insel B, Tsai WY, Hershman DL. Phase II study of glucosamine with chondroitin on aromatase inhibitor-associated joint symptoms in women with breast cancer. Support Care Cancer 201 PubMed
  43. Wilkens, P., Scheel, I. B., Grundnes, O., Hellum, C., and Storheim, K. Effect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: a randomized controlled trial. JAMA 2010;304(1):45-52. PubMed
  44. Simon RR, Marks V, Leeds AR, Anderson JW. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals. Diabetes Metab Res Rev 2011;27(1):14-27. PubMed
  45. Smidt D, Torpet LA, Nauntofte B, Heegaard KM, Pedersen AM. Associations between labial and whole salivary flow rates, systemic diseases and medications in a sample of older people. Community Dent Oral Epidemiol 2010;38(5):422-35. PubMed
  46. Wangroongsub Y, Tanavalee A, Wilairatana V, Ngarmukos S. Comparable clinical outcomes between glucosamine sulfate-potassium chloride and glucosamine sulfate sodium chloride in patients with mild and moderate knee osteoarthritis: a randomized, double-blind
  47. Chopra A, Saluja M, Tillu G, Venugopalan A, Sarmukaddam S, Raut AK, Bichile L, Narsimulu G, Handa R, Patwardhan B. A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of I
  48. Swinburne LM. Glucosamine sulphate and osteoarthritis. Lancet 2001;357(9268):1617. PubMed
  49. Murphy RK, Ketzler L, Rice RD, Johnson SM, Doss MS, Jaccoma EH. Oral glucosamine supplements as a possible ocular hypertensive agent. JAMA Ophthalmol 2013;131(7):955-7. PubMed
  50. Kimball AB, Kaczvinsky JR, Li J, et al. Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide and N-acetyl glucosamine: results of a randomized, double-blind, vehicle-controlled trial.
  51. Ma H, Li X, Sun D, et al. Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank. BMJ. 2019 May 14;365:l1628. PubMed
  52. Hoban C, Byard R, Musgrave I. Hypersensitive adverse drug reactions to glucosamine and chondroitin preparations in Australia between 2000 and 2011. Postgrad Med J. 2019 Oct 9. pii: postgradmedj-2019-136957. PubMed
  53. Tenti S, Veronese N, Cheleschi S, et al. Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study. Aging Clin Exp Res PubMed
  54. Yu H, Wu J, Chen H, et al. Glucosamine use is associated with a higher risk of cardiovascular diseases in patients with osteoarthritis: results from a large study in 685,778 subjects. Nutrients 2022;14(18):3694. PubMed
  55. Chu EC, Huang KHK, Cheung G, Ng G, Lin A. Delayed Skin Allergy to Glucosamine Chondroitin Supplement. Cureus 2023;15(3):e36310. PubMed
  56. Lila AM, Alekseeva LI, Baranov AA, et al. Chondroitin sulfate and glucosamine combination in patients with knee and hip osteoarthritis: A long-term observational study in Russia. World J Orthop 2023;14(6):443-457. PubMed
  57. Lehrer S, Morello T, Karrasch C, Rheinstein PH, Danias J. Effect of Glucosamine on Intraocular Pressure and Risk of Developing Glaucoma. J Glaucoma 2023. PubMed
  58. Rabade A, Viswanatha GL, Nandakumar K, Kishore A. Evaluation of efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis: a systematic review and meta-analysis. Inflammopharmac PubMed

See these in context on the Glucosamine monograph →

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

See these in context on the Gotu Kola monograph →

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 →

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 →

Shark Cartilage 12 references
  1. Ashar B, Vargo E. Shark cartilage-induced hepatitis [letter]. Ann Intern Med 1996;125:780-1. PubMed
  2. Lane IW, Comac L. Sharks don't get cancer. Garden City, NY: Avery Publishing Group; 1992.
  3. Miller DR, Anderson GT, Stark JJ, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998;16:3649-55. PubMed
  4. Leitner SP, Rothkopf MM, Haverstick L, et al. Two phase II studies of oral dry shark cartilage powder (SCP) in patients (pts) with either metastatic breast or prostate cancer refractory to standard treatment. Proc Am Soc Clinical Oncol 1998;17:A240.
  5. Batist G, Patenaude F, Champagne P, et al. Neovastat (AE-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels. Ann Oncol 2002;13:1259-63..
  6. Merly, L., Simjee, S., and Smith, S. L. Induction of inflammatory cytokines by cartilage extracts. Int Immunopharmacol. 2007;7(3):383-391. PubMed
  7. Bargahi, A., Hassan, Z. M., Rabbani, A., Langroudi, L., Noori, S. H., and Safari, E. Effect of shark cartilage derived protein on the NK cells activity. Immunopharmacol.Immunotoxicol. 2011;33(3):403-409. PubMed
  8. Leitner SP, Rothkopf MM, Haverstick DD, and et al. Two phase II studies of oral dry shark cartilage powder (SCP) in patients with either metastatic breast or prostate cancer refractory to standard treatment. Amer Soc Clin Oncol 1998;17:A240.
  9. Milner M. A guide to the use of shark cartilage in the treatment of arthritis and other inflammatory joint diseases. Amer Chiropractor 1999;21:40-42.
  10. Rosenbluth, RJ, Jennis, AA, Cantwell, S, and et al. Oral shark cartilage in the treatment of patients with advanced primary brain tumors. A phase II pilot study (meeting abstract). Proc Annu Meet Am Soc Clin Oncol 1999;18:A554.
  11. Saad F, Klotz L, Babaian R, Lacombe L, Champagne P, and Dupont E. Phase I/II trial on AE-941 (Neovastat) in patients with metastatic refractory prostate cancer (abstract presentation). Canadian Urological Association Annual Meeting (June 24-27, 2001).
  12. Merly L, Smith SL. Pro-inflammatory properties of shark cartilage supplement. Immunopharmacol Immunotoxicol. 2015;37(2):140-7. PubMed

See these in context on the Shark Cartilage monograph →

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

See these in context on the Green Tea monograph →

Wild Yam 7 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. Eagon PK, Elm MS, Hunter DS, et al. Medicinal herbs: modulation of estrogen action. Era of Hope Mtg, Dept Defense; Breast Cancer Res Prog, Atlanta, GA 2000;Jun 8-11.
  3. Cheong JL, Bucknall R. Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient. Postgrad Med J 2005;81:266-7.. PubMed
  4. Rosenberg Zand, R. S., Jenkins, D. J., and Diamandis, E. P. Effects of natural products and nutraceuticals on steroid hormone-regulated gene expression. Clin Chim.Acta 2001;312(1-2):213-219. PubMed
  5. Araghiniknam M, Chung S, Nelson-White T, and et al. Antioxidant activity of Dioscorea and dehydroepiandrosterone (DHEA) in older humans. Life Sciences 1996;59:L147-L157.
  6. Zeng M, Zhang L, Li M, et al. Estrogenic effects of the extracts from the Chinese Yam (Dioscorea opposite Thunb.) and its effective compounds in vitro and in vivo. Molecules. 2018 Jan 23;23(2). Pii: E11. PubMed
  7. Lu J, Wong RN, Zhang L, et al. Comparative analysis of proteins with stimulating activity on ovarian estradiol biosynthesis from four different Dioscorea species in vitro using both phenotypic and target-based approaches: implication for treating menopaus

See these in context on the Wild Yam monograph →

Butcher's Broom 8 references
  1. Beltramino R, Penenory A, Buceta AM. An open-label, randomized multicenter study comparing the efficacy and safety of Cyclo 3 Fort versus hydroxyethyl rutoside in chronic venous lymphatic insufficiency. Angiology 2000;51:535-44.. PubMed
  2. Redman DA. Ruscus aculeatus (butcher's broom) as a potential treatment for orthostatic hypotension, with a case report. J Altern Complement Med 2000;6:539-49..
  3. Landa, N., Aguirre, A., Goday, J., Raton, J. A., and Diaz-Perez, J. L. Allergic contact dermatitis from a vasoconstrictor cream. Contact Dermatitis 1990;22(5):290-291. PubMed
  4. Cluzan, R. V., Alliot, F., Ghabboun, S., and Pascot, M. Treatment of secondary lymphedema of the upper limb with CYCLO 3 FORT. Lymphology 1996;29(1):29-35.
  5. Parrado F, Buzzi A. A study of the efficacy and tolerability of a preparation containing Ruscus aculeatus in the treatment of chronic venous insufficiency of the lower limbs. Clin Drug Invest 1999;18(4):255-61. DOI
  6. Sadarmin PP, Timperley J. An unusual case of Butcher's Broom precipitating diabetic ketoacidosis. J Emerg Med 2013;45(3):e63-e65. PubMed
  7. Ramirez-Hernandez M, Garcia-Selles J, Merida-Fernandez C, Martinez-Escribano JA. Allergic contact dermatitis to ruscogenins. Contact Dermatitis 2006;54(1):60. PubMed
  8. European Medicines Agency. Assessment report on Ruscus Aculeatus L rhizome. EMEA/HMPC/261939/2007. London, September 4, 2008. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2009/12/WC500018288.pdf. Acces

See these in context on the Butcher's Broom monograph →

Calcium 62 references
  1. Shils M, Olson A, Shike M. Modern Nutrition in Health and Disease. 8th ed. Philadelphia, PA: Lea and Febiger, 1994.
  2. Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, et al. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology 2003;14:206-12.. PubMed
  3. Thys-Jacobs S, Ceccarelli S, Bierman A, et al. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med 1989;4:183-9. PubMed
  4. Maton PN, Burton ME. Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs 1999;57:855-70.
  5. Clemens JD, Feinstein AR. Calcium carbonate and constipation: a historical review of medical mythopoeia. Gastroenterology 1977;72:957-61. DOI
  6. Saunders D, Sillery J, Chapman R. Effect of calcium carbonate and aluminum hydroxide on human intestinal function. Dig Dis Sci 1988;33:409-13. PubMed
  7. Friedman PA, Bushinsky DA. Diuretic effects on calcium metabolism. Semin Nephrol 1999;19:551-6.
  8. Koo WK, Walters JC, Esterlitz J, et al. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol 1999;94:577-82. DOI
  9. Raman L, Rajalakshmi K, Krishnamachari KAVR, et al. Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the neonates. Am J Clin Nutr 1978; 31:466-9. DOI
  10. Murry JJ, Healy MD. Drug-mineral interactions: a new responsibility for the hospital dietician. J Am Diet Assoc 1991;91:66-73.
  11. Chan JM, Giovannucci E, Andersson SO, et al. Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer. Cancer Causes Control 1998;9:559-66.
  12. Butner LE, Fulco PP, Feldman G, et al. Calcium carbonate-induced hypothyroidism. Ann Intern Med 2000:132:595. PubMed
  13. Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA 1998;279:750. PubMed
  14. Moser LR, Smythe MA, Tisdale JE. The use of calcium salts in the prevention and management of verapamil-induced hypotension. Ann Pharmacother 2000;34:622-9. PubMed
  15. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000;283:2822-5. PubMed
  16. Kahela P, Anttila M, Tikkanen R, Sundquist H. Effect of food, food constituents and fluid volume on the bioavailability of sotalol. Acta Pharmacol Toxicol (Copenh) 1979;44:7-12.. PubMed
  17. Pletz MW, Petzold P, Allen A, et al. Effect of calcium carbonate on bioavailability of orally administered gemifloxacin. Antimicrob Agents Chemother 2003;47:2158-60.. PubMed
  18. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  19. Decktor DL, Robinson M, Maton PN, et al. Effects of aluminum/magnesium hydroxide and calcium carbonate on esophageal and gastric pH in subjects with heartburn. Am J Ther 1995;2:546-52. PubMed
  20. Simoneau G. Absence of rebound effect with calcium carbonate. Eur J Drug Metab Pharmacokinet 1996;21:351-7. PubMed
  21. Peters ML, Leonard M, Licata AA. Role of alendronate and risedronate in preventing and treating osteoporosis. Cleve Clin J Med 2001;68:945-51. PubMed
  22. Bourke JF, Mumford R, Whittaker P, et al. The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis. J Am Acad Dermatol 1997;37:929-34.
  23. Gueguen L, Pointillart A. The bioavailability of dietary calcium. J Am Coll Nutr 2000;19:119s-136s. PubMed
  24. Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J 1999;75:554-6. PubMed
  25. Bania TC, Blaufeux B, Hughes S, et al. Calcium and digoxin vs. calcium alone for severe verapamil toxicity. Acad Emerg Med 2000;7:1089-96. PubMed
  26. Tseng M, Breslow RA, Graubard BI, Ziegler RG. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr 2005;81:1147-54. PubMed
  27. Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2004;(1):CD003548. PubMed
  28. Tavani A, Bertuccio P, Bosetti C, et al. Dietary intake of calcium, vitamin D, phosphorus and the risk of prostate cancer. Eur Urol 2005;48:27-33. PubMed
  29. Giovannucci E, Liu Y, Stampfer MJ, Willett WC. A prospective study of calcium intake and incident and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev 2006;15:203-10. PubMed
  30. Rocephin (ceftriaxone) and calcium interaction. Pharmacist's Letter / Prescriber's Letter 2007;23(10):231005.
  31. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised control trial. BMJ 2008;336:262-6.
  32. Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691. PubMed
  33. Calcium supplementation and vascular events. Pharmacist's Letter / Prescriber's Letter 2008;24(3):240306.
  34. 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
  35. Coburn JW, Mischel MG, Goodman WG, et al. Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis. 1991;17(6):708-11. PubMed
  36. Bradley JS, Wassel RT, Lee L, et al. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics. 2009;123(4):e609-13. PubMed
  37. Kays MB, Overholser BR, Mueller BA, et al. Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin. Am J Kidney Dis. 2003;42(6):1253-9. PubMed
  38. Neuhofel, A. L., Wilton, J. H., Victory, J. M., Hejmanowsk, L. G., and Amsden, G. W. Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction. J Clin Pharmacol. 2002;42(4):461-466. DOI
  39. Dickinson, H. O., Nicolson, D. J., Cook, J. V., Campbell, F., Beyer, F. R., Ford, G. A., and Mason, J. Calcium supplementation for the management of primary hypertension in adults. Cochrane.Database.Syst.Rev. 2006;(2):CD004639. PubMed
  40. Jones, B. J. and Twomey, P. J. Requesting patterns for serum calcium concentration in patients on long-term lithium therapy. Int J Clin Pract. 2009;63(1):170-172. PubMed
  41. Levine, M., Nikkanen, H., and Pallin, D. J. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg.Med. 2011;40(1):41-46. PubMed
  42. Castelo-Branco, C., Ciria-Recasens, M., Cancelo-Hidalgo, M. J., Palacios, S., Haya-Palazuelos, J., Carbonell-Abello, J., Blanch-Rubio, J., Martinez-Zapata, M. J., Manasanch, J., and Perez-Edo, L. Efficacy of ossein-hydroxyapatite complex compared with ca
  43. Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation i
  44. Chung M, Tang AM, Fu Z. Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Ann Intern Med. 2016 Oct 25. PubMed
  45. Nolan CR, Califano JR, Butzin CA. Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int. 1990;38(5):937-41. PubMed
  46. Lewis JR, Radavelli-Bagatini S, Rejnmark L, et al. The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials. J Bone Miner Res PubMed
  47. 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
  48. 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
  49. Grove ML, Cook D. Calcium and heart attacks. Doesn't apply to most calcium prescriptions. BMJ. 2010;341:c5003. PubMed
  50. Insentress [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2014.
  51. Roberts JL, Kiser JJ, Hindman JT, Meditz AL. Virologic failure with a raltegravir-containing antiretroviral regimen and concomitant calcium administration. Pharmacotherapy 2011;31(10):298e-302e. DOI
  52. Vitekta [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2014.
  53. Storan ER, O'Gorman SM, Murphy A, Laing M. Case Report of Calciphylaxis Secondary to Calcium and Vitamin D<sub>3</sub> Supplementation. J Cutan Med Surg. 2017;21(2):162-163. DOI
  54. 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
  55. Borkenhagen JF, Connor EL, Stafstrom CE. Neonatal hypocalcemic seizures due to excessive maternal calcium ingestion. Pediatr Neurol 2013;48(6):469-71. PubMed
  56. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/ anc-positive-pregnancy-experience/en/).
  57. Aune D, Navarro Rosenblatt DA, Chan DS, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr. 2015;101(1):87-117. PubMed
  58. Lan T, Park Y, Colditz GA, et al. Adolescent dairy product and calcium intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study. Cancer Causes Control. 2020;31(10):891-904. PubMed
  59. Zhang Y, Li Y, Liu J, et al. Association of Vitamin D or Calcium Supplementation with Cardiovascular Outcomes and Mortality: A Meta-Analysis with Trial Sequential Analysis. J Nutr Health Aging 2021;25(2):263-270. PubMed
  60. Myung SK, Kim HB, Lee YJ, Choi YJ, Oh SW. Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials. Nutrients 2021;13(2):368. PubMed
  61. Hetaimish B. Neonatal Calcinosis Cutis After Treatment of Hypocalcemia with Calcium Gluconate: A Report of 2 Cases. Am J Case Rep 2024;25:e943397. PubMed
  62. 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.

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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.

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