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Dietary supplement

Energy Formula Ingredients & Drug Interactions

by GNC SuperFoods

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

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

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

The interaction bottom line Most serious interaction: Major

Energy Formula is a dietary supplement by GNC SuperFoods with 4 active ingredients. Its ingredients are commonly taken for energy and alertness, reducing fatigue, weight loss support.Based on those ingredients, 1,584 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Tea leaf extract, Ginkgo biloba leaf extract, Cocoa seed powder. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Energy Formula by GNC SuperFoods

Ask about any prescription or over-the-counter medication and we check it for interactions with Energy Formula by GNC SuperFoods — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Energy Formula by GNC SuperFoods

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

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 23, 2026

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 4 of its 4 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

GNC SuperFoods Energy Formula contains four active ingredients. Guarana seed extract and green tea leaf extract are both sources of caffeine and are included for their energizing properties.

Cocoa seed powder adds flavor and also contains caffeine alongside compounds that may support heart health. Ginkgo biloba leaf extract is traditionally used to support mental clarity and blood flow.

The formula also contains several inactive ingredients—cellulose, a vegetable cellulose capsule, magnesium stearate, silicon dioxide, and chlorophyll—which serve as fillers, binders, and capsule material.

Does it work?

Strong 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

This product doesn't appear to be marketed for a specific use, so we graded its ingredients' overall clinical evidence instead.

Strong

Strong clinical evidence supports its ingredients for:

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredients' overall clinical evidence instead.
  • On file: Human papillomavirus (HPV) — rated "Likely Effective" (Green Tea) (Natural Medicines).
  • On file: Anxiety — rated "Possibly Effective" (Ginkgo) (Natural Medicines).
  • On file: Cardiovascular disease (CVD) — rated "Possibly Effective" (Cocoa) (Natural Medicines).
  • On file: Dementia — rated "Possibly Effective" (Ginkgo) (Natural Medicines).
  • On file: Endometrial cancer — rated "Possibly Effective" (Green Tea) (Natural Medicines).

The evidence for this product's ingredients varies. Green tea shows the strongest support, with likely effectiveness for human papillomavirus (HPV) prevention and possibly effective ratings for ovarian cancer and cholesterol management.

Cocoa and ginkgo are both possibly effective for cardiovascular health. Ginkgo is also possibly effective for hearing loss, stroke recovery, schizophrenia, premenstrual syndrome, dementia, and anxiety.

Guarana, however, has insufficient evidence for cancer-related appetite loss, anxiety, athletic performance, and cancer-related fatigue. Overall, if you're taking this product hoping it will boost your energy, the evidence that it does so is not established in the data we hold.

The evidence, ingredient by ingredient Guarana Green Tea Cocoa Ginkgo

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 4 of the 4 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 4 of 4.
  • General safety write-ups exist for 4 of 4.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Guarana, green tea, and cocoa are all generally well tolerated when used in moderation, but their high caffeine content can cause problems with overuse. The most common side effects are gastrointestinal—nausea, stomach burning, bloating, diarrhea, and constipation—along with dizziness, insomnia, nervousness, and headache, especially with larger doses.

Ginkgo leaf extract is also generally well tolerated in healthy adults when used for up to six years; the most common side effects are dizziness and gastrointestinal discomfort. However, ginkgo carries a rare but serious risk of bleeding and cardiac arrhythmias.

Anaphylaxis (a severe allergic reaction) has been reported rarely with both caffeine and green tea proteins in sensitive individuals. During pregnancy, guarana and green tea are rated possibly unsafe because of their high caffeine content, and ginkgo should be avoided due to insufficient safety data and bleeding risk.

While breastfeeding, caffeine from guarana, green tea, and cocoa passes into breast milk, so intake should be limited and your baby watched for fussiness; ginkgo should be avoided while breastfeeding.

Side effects, ingredient by ingredient Guarana Green Tea Cocoa Ginkgo

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?
  • 4 of the 4 matched ingredients can interact with medications — Ginkgo, Cocoa, Guarana, Green Tea.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; immunosuppressants / transplant drugs; diabetes medications; lithium.
  • For scale: 1,585 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 this product, check with your doctor or pharmacist if you take any of the following: ephedrine or other stimulants (Major risk), nadolol or atorvastatin (Major risk, as the product may cut their effectiveness significantly), antiepileptic drugs such as valproate, felbamate, carbamazepine, ethosuximide, or phenytoin (Moderate risk), blood thinners like warfarin (Moderate risk of increased bleeding), clozapine or other antipsychotics (Moderate risk), fluvoxamine or other antidepressants (Moderate risk), disulfiram (Moderate risk), dipyridamole (Moderate risk), pentobarbital or other sedatives (Moderate risk), quinolone antibiotics (Moderate risk), blood pressure medications (Moderate risk), beta-agonists for asthma (Moderate risk), alprazolam or other benzodiazepines (Moderate risk), simvastatin (Moderate risk), trazodone (Moderate risk), efavirenz (Moderate risk), rosiglitazone (Moderate risk), or tacrolimus (Moderate risk).

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with strong clinical evidence behind its ingredients' uses. Major medication interactions have been identified, and safety information is well characterized.

This product may appeal to someone looking for a natural energy boost, particularly if they're drawn to the cardiovascular or cognitive benefits that green tea, cocoa, and ginkgo may offer. However, because it contains significant caffeine and multiple medications interact with its ingredients—some seriously—you need to check your prescription medications with your doctor or pharmacist before starting.

Avoid it entirely if you take ephedrine, blood thinners like warfarin, antiepileptic drugs, antipsychotics, or certain heart or cholesterol medications.

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

Assessment coverage: 4 of 4 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Dec 23, 2016.

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 Energy Formula, straight from the product label.

Brand GNC SuperFoods
Net contents 30 Pack(s)
Market status On market
Date entered into DSLD Dec 23, 2016
DSLD ID 67281
Product type Botanical
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult Female (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Energy Formula by GNC SuperFoods, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Dark Green Capsule(s)
Maximum serving Sizes:
1 Dark Green Capsule(s)
IngredientAmount% DV
Guarana seed extract70 mg--
Green Tea leaf extract50 mg--
Cocoa seed powder50 mg--
Ginkgo biloba leaf extract50 mg--

Other ingredients: Cellulose, Vegetable Cellulose Capsule, Magnesium Stearate, Silicon Dioxide, Chlorophyll

Tap any ingredient to jump to its full detail below.

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

GNC Guarantee If you are not 100% completely satisfied, return the unused portion of the product with your receipt to a GNC store within 30 days. Our trained sales staff will either refund your purchase price or, if you prefer, assist you in finding a replacement product to help you live well.

GNC Quality Commitment For more than 79 years, GNC has been the leader in the development of superior nutritional supplements. Our products are produced using only fresh, high-quality ingredients and are manufactured under the strictest quality controls.

Made with cultured vitamins and minerals, clinically researched ingredients and fruits and vegetables.

Clinically researched

New!

Provides performance, recover, beauty and antioxidant support

Performance

Actual size

Each pack contains: Energy Formula

Conforms to USP <2091> for weight. Meets USP <2040> disintegration.

Formulation

No artificial colors, no artificial flavors, no artificial sweeteners, no wheat, gluten free, no soy, no dairy.

Vegetarian formula

Non GMO

Gluten free

Seals/Symbols

V Vegetarian formula

Non GMO

Gf Gluten free

FDA Statement of Identity

Dietary Supplement

Brand IP Statement(s)

Whole food enhanced Vitapak program

Formula

Contains caffeine from naturally energizing tea and guarana to support exercise performance, and an array of B vitamins needed for energy production.

Contains 50 mg of caffeine.

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.

Precautions

Contains 50 mg of caffeine.

Keep out of reach of children.

Warning: Consult your physician prior to using this product if you are pregnant, nursing, taking medication, or have a medical condition.

Discontinue use two weeks prior to surgery.

General

CODE 204111 AQG

Suggested/Recommended/Usage/Directions

Directions: As a dietary supplement, take the contents of one pack daily with food.

Storage

Store in a cool, dry place.

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

See for yourself

Energy Formula by GNC SuperFoods label

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

Energy Formula label

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

View the full label (PDF)
What’s inside

The Ingredients in Energy Formula by GNC SuperFoods

These are the 4 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Dark Green Capsule(s) Dosage formCapsule 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.

Guarana seed extract

Interacts with
655 drugs
70 mg per serving Form: Caffeine

Guarana is an Amazonian seed that is naturally high in caffeine, which explains most of its stimulant and energy effects. While it may give a short-te...

Guarana seed extract monograph & interactions

Green Tea leaf extract

Interacts with
1,293 drugs
50 mg per serving Form: Caffeine

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

Green Tea leaf extract monograph & interactions

Cocoa seed powder

Interacts with
661 drugs
50 mg per serving

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

Cocoa seed powder monograph & interactions

Ginkgo biloba leaf extract

Interacts with
1,266 drugs
50 mg per serving Form: Ginkgo Flavone Glycosides, Terpene Lactones

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

Ginkgo biloba leaf extract monograph & interactions

Other (inactive) ingredients: Cellulose, Vegetable Cellulose Capsule, Magnesium Stearate, Silicon Dioxide, Chlorophyll. These complete the product’s ingredient list but are not active constituents.

Interaction report

Energy Formula by GNC SuperFoods Drug Interactions

Want to check YOUR meds against Energy Formula?

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
1,584Drugs
14 Major 1,563 Moderate 7 Minor

Ingredients driving the most interactions

Green Tea leaf extract 1,293
Ginkgo biloba leaf extract 1,266
Cocoa seed powder 661
Guarana seed extract 655

Individual Drug Interactions

The ingredients in Energy Formula interact with 1,584 drugs. Click any drug to see the details.

4 of the 4 ingredients in Energy Formula interact with drugs. Each result below shows which ingredient is responsible. Green Tea leaf extract Ginkgo biloba leaf extract Cocoa seed powder Guarana seed extract

Each ingredient & the kinds of drugs it affects

For each ingredient in Energy Formula 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 leaf extract58 drug types · 1,293 drugs

Atorvastatin (Lipitor)

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

Likelihood Likely Evidence B
Ephedrine

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

Likelihood Probable Evidence D
Nadolol (Corgard)

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

Likelihood Likely Evidence B
5-Fluorouracil

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

Likelihood Possible Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

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

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

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

Likelihood Probable Evidence D
Bortezomib (Velcade)

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

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

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

Likelihood Possible Evidence D
Celiprolol (Celicard)

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

Likelihood Possible Evidence D
Cimetidine (Tagamet)

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

Likelihood Likely Evidence B
Clozapine (Clozaril)

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

Likelihood Possible Evidence B
Contraceptive Drugs

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

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

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

Likelihood Possible Evidence D
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

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

Likelihood Possible Evidence D
Felbamate (Felbatol)

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

Likelihood Possible Evidence D
Fexofenadine (Allegra)

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

Likelihood Probable Evidence B
Flutamide (Eulexin)

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

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Hepatotoxic Drugs

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

Likelihood Unlikely Evidence D
Imatinib (Gleevec)

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

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

Ginkgo biloba leaf extract23 drug types · 1,266 drugs

Talinolol

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

Likelihood Probable Evidence B
Alprazolam (Xanax)

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

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence A
Anticonvulsants

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

Likelihood Possible Evidence D
Antidiabetes Drugs

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

Likelihood Possible Evidence B
Atorvastatin (Lipitor)

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

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

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

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

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

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

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

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

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

Likelihood Possible Evidence B
Efavirenz (Sustiva)

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

Likelihood Possible Evidence D
Ibuprofen (Advil, Others)

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

Likelihood Possible Evidence D
P-Glycoprotein Substrates

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

Likelihood Possible Evidence B
Risperidone (Risperdal)

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

Likelihood Possible Evidence D
Rosiglitazone (Avandia)

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

Likelihood Possible Evidence D
Seizure Threshold Lowering Drugs

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

Likelihood Possible Evidence D
Simvastatin (Zocor)

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

Likelihood Probable Evidence B
Sofosbuvir (Sovaldi)

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

Likelihood Possible Evidence D
Tacrolimus (Prograf)

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

Likelihood Possible Evidence D
Trazodone (Desyrel)

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

Likelihood Possible Evidence D
Warfarin (Coumadin)

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

Likelihood Possible Evidence B
Nifedipine (Procardia)

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

Likelihood Possible Evidence B
Omeprazole (Prilosec)

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

Likelihood Possible Evidence B
Ginkgo biloba leaf extract full monograph & interactions

Cocoa seed powder37 drug types · 661 drugs

Ace Inhibitors (Aceis)

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

Likelihood Possible Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Alcohol (Ethanol)

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Antihypertensive Drugs

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

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

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

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

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

Likelihood Possible Evidence D
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Ephedrine

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Flutamide (Eulexin)

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

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

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

Likelihood Possible Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenylpropanolamine

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

Likelihood Probable Evidence B
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Stimulant Drugs

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

Likelihood Probable Evidence C
Theophylline

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

Likelihood Probable Evidence B
Cocoa seed powder full monograph & all 37 interactions

Guarana seed extract41 drug types · 655 drugs

Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Guarana contains caffeine. Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects. 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
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, guarana may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that guarana extract can inhibit platelet aggregation. This effect may be due to the caffeine in guarana, which is also reported to have antiplatelet activity. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

Theoretically, concomitant use might increase the clinical effects of beta-adrenergic agonists.
Guarana contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

Theoretically, guarana might reduce the effects of carbamazepine and increase the risk for convulsions.
Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when given to animals 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 two-fold in healthy individuals.

Likelihood Possible Evidence D
Cimetidine (Tagamet)

Theoretically, concomitant use might increase the effects and adverse effects of caffeine in guarana.
Guarana contains caffeine. Cimetidine decreases the rate of caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Theoretically, guarana might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Guarana contains caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg per day 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 more sensitive to the interaction between clozapine and caffeine.

Likelihood Possible Evidence B
Dipyridamole (Persantine)

Theoretically, guarana might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Guarana 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 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 D
Diuretic Drugs

Theoretically, using guarana with diuretic drugs might increase the risk of hypokalemia.
Guarana contains caffeine. Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump. Diuretics can also lower potassium levels.

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, guarana might reduce the effects of ethosuximide and increase the risk for convulsions.
Guarana contains caffeine. Animal research shows that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. This effect has not been observed in humans.

Likelihood Possible Evidence D
Felbamate (Felbatol)

Theoretically, guarana might reduce the effects of felbamate and increase the risk for convulsions.
Guarana contains caffeine. Animal research shows that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. This effect has not been observed in humans.

Likelihood Possible Evidence D
Flutamide (Eulexin)

Theoretically, guarana might increase the levels and adverse effects of flutamide.
Guarana contains caffeine. In vitro evidence shows that caffeine can inhibit the metabolism of flutamide. However, this effect has not been reported in humans.

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

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

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Guarana contains caffeine. Caffeine has been shown to inhibit MAO-A and -B in laboratory studies. Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis. In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension. Hypertension was resolved after the patient switched to drinking decaffeinated coffee.

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence D
Pentobarbital (Nembutal)

Theoretically, guarana might decrease the effects of pentobarbital.
Guarana contains caffeine. In vivo evidence suggests that caffeine can negate the hypnotic effects of pentobarbital in humans. However, animal research suggests that guarana does not alter the hypnotic effect of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenylpropanolamine

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

Likelihood Probable Evidence B
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Pioglitazone (Actos)

Theoretically, guarana might increase the levels and clinical effects of pioglitazone.
Guarana contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Riluzole (Rilutek)

Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Guarana contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce the metabolism of one or both agents.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.
Guarana contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects.

Likelihood Possible Evidence D
Guarana seed extract full monograph & all 41 interactions
The maker

Brand information

Manufacturer and brand details for Energy Formula, from the product label.

GNC SuperFoods

See all GNC SuperFoods products
Name
General Nutrition Corp.
City
Pittsburgh
State
PA
ZipCode
15222
Phone Number
1-888-462-2548
Web Address
www.gnc.com
Pharmacist Counseling Corner

Energy Formula by GNC SuperFoods: Common Questions

Does Energy Formula by GNC SuperFoods interact with any medications?
Yes. Based on its ingredients, Energy Formula has a known interaction with 1,584 medications, including 14 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Energy Formula contains 4 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take this if I'm pregnant or breastfeeding?
No. Guarana and green tea are rated possibly unsafe in pregnancy because of their high caffeine content, and ginkgo should be avoided due to insufficient safety data and a possible bleeding risk. If you're breastfeeding, caffeine from guarana, green tea, and cocoa passes into breast milk and could make your baby fussy, and ginkgo's safety hasn't been established. Talk with your doctor or pharmacist before taking this product during pregnancy or while nursing.
What are the most common side effects?
The most common side effects come from the caffeine content: nausea, stomach upset, bloating, diarrhea, constipation, dizziness, insomnia, nervousness, and headache. These are more likely with larger doses or in people sensitive to caffeine. Ginkgo may also cause dizziness and gastrointestinal discomfort.
Will this really give me more energy?
Guarana, green tea, and cocoa all contain caffeine, which is a stimulant, so they may provide a short-term boost. However, we don't have reliable evidence that guarana itself is effective for athletic performance or fatigue in the data we hold.
Is this safe to use long-term?
Ginkgo leaf extract has been studied for up to six years and appears well tolerated, and green tea extract has been studied for up to 12 months. However, because of the product's high caffeine content and potential medication interactions, you should talk with your doctor or pharmacist about whether long-term use is appropriate for your individual situation.
What is ginkgo biloba supposed to do in this formula?
Ginkgo biloba is traditionally used to support mental clarity, blood flow, and cognitive function. In the data we hold, it's rated possibly effective for hearing loss, stroke recovery, schizophrenia, premenstrual syndrome, dementia, and anxiety.
Does this product have any fillers?
Yes. The product contains inactive ingredients including cellulose, magnesium stearate, silicon dioxide, and chlorophyll, which serve as binders, fillers, and capsule material to hold the active ingredients together.

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.

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Go deeper

The Full Monographs Behind Energy Formula’s Ingredients

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

Herb & supplement monograph

Guarana

Interacts with 655 drugs

Guarana is an Amazonian seed that is naturally high in caffeine, which explains most of its stimulant and energy effects. While it may give a short-term boost in alertness and reduce fatigue...

Read the full Guarana 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

Cocoa

Interacts with 661 drugs

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

Read the full Cocoa monograph → Herb & supplement monograph

Ginkgo

Interacts with 1,266 drugs

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

Read the full Ginkgo monograph →
Sources

Sources & How We Checked

Energy Formula'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 549 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.

Guarana 114 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. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  8. 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.
  9. 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
  10. 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
  11. 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
  12. 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.
  13. 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
  14. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  15. 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
  16. 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
  17. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. PubMed
  18. 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
  19. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  20. Boozer CN, Nasser JA, Heymsfield SB, et al. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001;25:316-24. PubMed
  21. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  22. 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
  23. Tobias JD. Caffeine in the treatment of apnea associated with respiratory syncytial virus infection in neonates and infants. South Med J 2000;93:297-304. DOI
  24. 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
  25. 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
  26. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  27. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  28. 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
  29. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  37. 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
  38. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  39. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  40. Schechter MD, Timmons GD. Objectively measured hyperactivity--II. Caffeine and amphetamine effects. J Clin Pharmacol 1985;25:276-80.. PubMed
  41. 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
  42. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  43. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  44. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  45. 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
  46. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. PubMed
  47. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  48. 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
  49. 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
  50. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  51. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  52. 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
  53. 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.
  54. 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
  55. Holmgren P, Norden-Pettersson L, Ahlner J. Caffeine fatalities--four case reports. Forensic Sci Int 2004;139:71-3. PubMed
  56. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  57. 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
  58. Leson CL, McGuigan MA, Bryson SM. Caffeine overdose in an adolescent male. J Toxicol Clin Toxicol 1988;26:407-15. PubMed
  59. 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
  60. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  61. 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
  62. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  63. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  64. 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
  65. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  66. Mansi IA, Huang J. Rhabdomyolysis in response to weight-loss herbal medicine. Am J Med Sci 2004;327:356-357. PubMed
  67. Spinella M. Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects. Epilepsy Behav 2001;2(6):524-532. PubMed
  68. 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.
  69. 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
  70. 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
  71. 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
  72. 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
  73. 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
  74. 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.
  75. 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
  76. 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
  77. 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.
  78. 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
  79. 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.
  80. 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
  81. 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
  82. 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.
  83. 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
  84. Quirce, G. S., Freire, P., Fernandez, R. M., Davila, I., and Losada, E. Urticaria from caffeine. J.Allergy Clin Immunol. 1991;88(4):680-681. PubMed
  85. Wrenn, K. D. and Oschner, I. Rhabdomyolysis induced by a caffeine overdose. Ann.Emerg.Med. 1989;18(1):94-97. PubMed
  86. Pola, J., Subiza, J., Armentia, A., Zapata, C., Hinojosa, M., Losada, E., and Valdivieso, R. Urticaria caused by caffeine. Ann.Allergy 1988;60(3):207-208.
  87. Caballero, T., Garcia-Ara, C., Pascual, C., Diaz-Pena, J. M., and Ojeda, A. Urticaria induced by caffeine. J.Investig.Allergol.Clin Immunol. 1993;3(3):160-162.
  88. 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
  89. 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
  90. 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
  91. 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
  92. 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
  93. 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
  94. 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
  95. 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
  96. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  97. 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
  98. du, Boisgueheneuc F., Lannuzel, A., Caparros-Lefebvre, D., and De Broucker, T. [Cerebral infarction in a patient consuming MaHuang extract and guarana]. Presse Med 2-3-2001;30(4):166-167.
  99. Baghkhani, L. and Jafari, M. Cardiovascular adverse reactions associated with Guarana: is there a causal effect? J.Herb.Pharmacother. 2002;2(1):57-61. DOI
  100. Haller, C. A., Jacob, P., and Benowitz, N. L. Short-term metabolic and hemodynamic effects of ephedra and guarana combinations. Clin.Pharmacol.Ther. 2005;77(6):560-571. PubMed
  101. Bydlowski, S. P., D'Amico, E. A., and Chamone, D. A. An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis. Braz.J.Med.Biol.Res. 1991;24(4):421-424.
  102. Bydlowski, S. P., Yunker, R. L., and Subbiah, M. T. A novel property of an aqueous guarana extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo. Braz.J.Med.Biol.Res. 1988;21(3):535-538.
  103. Galduroz, J. C. and Carlini, E. A. The effects of long-term administration of guarana on the cognition of normal, elderly volunteers. Sao Paulo Med.J. 1996;114(1):1073-1078. PubMed
  104. Mattei, R., Dias, R. F., Espinola, E. B., Carlini, E. A., and Barros, S. B. Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro. J.Ethnopharmacol. 1998;60(2):111-116.
  105. Chamone, D. A., Silva, M. I., Cassaro, C., Bellotti, G., Massumoto, C. M., and Fujimura, A. Y. Guaraná (Paullinia cupana) inhibits aggregation in whole blood. Thrombosis and Haemostasis 1987;58(1):474.
  106. 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
  107. del Giglio AB, Cubero Dde I, Lerner TG, Guariento RT, de Azevedo RG, Paiva H, Goldman C, Carelli B, Cruz FM, Schindler F, Pianowski L, de Matos LL, del Giglio A. Purified dry extract of Paullinia cupana (guaraná) (PC-18) for chemotherapy-related fatigue i
  108. Palma CG, Lera AT, Lerner T, de Oliveira MM, de Borta TM, Barbosa RP, Brito GM, Guazzelli CA, Cruz FJ, del Giglio A. Guarana (Paullinia cupana) Improves Anorexia in Patients with Advanced Cancer. J Diet Suppl. 2016;13(2):221-31.
  109. 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
  110. de Araujo DP, Pereira PTVT, Fontes AJC, et al. The use of guarana (Paullinia cupana) as a dietary supplement for fatigue in cancer patients: a systematic review with a meta-analysis. Support Care Cancer 2021;29(12):7171-7182. PubMed
  111. 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
  112. 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
  113. 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
  114. 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

See these in context on the Guarana 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 →

Cocoa 119 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  3. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  4. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
  5. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  6. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  7. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  8. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  9. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  10. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  11. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  12. Baron AM, Donnerstein RL, Samson RA, et al. Hemodynamic and electrophysiologic effects of acute chocolate ingestion in young adults. Am J Cardiol 1999;84:370-3. PubMed
  13. Friedman G. Diet and the irritable bowel syndrome. Gastroenterol Clin North Am 1991;20:313-24. DOI
  14. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  15. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  16. Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
  17. Weisburger JH. Tea and health: the underlying mechanisms. Proc Soc Exp Biol Med 1999;220:271-5. PubMed
  18. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  19. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  20. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  21. Dietrich R, Paglieroni TG, Wun T, et al. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000;72:30-5. PubMed
  22. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  23. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  24. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  25. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI
  26. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  27. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. PubMed
  28. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  29. Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. DOI
  30. Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. PubMed
  31. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  32. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  33. Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. PubMed
  34. Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7.
  35. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
  36. Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. PubMed
  37. Vlachopoulos C, Aznaouridis K, Alexopoulos N, et al. Effect of dark chocolate on arterial function in healthy individuals. Am J Hypertens 2005;18:785-91.. PubMed
  38. Taubert D, Berkels R, Roesen R, Klaus W. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA 2003;290:1029-30.. PubMed
  39. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  40. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  41. Grassi D, Necozione S, Lippi C, et al. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 2005;46:398-405. PubMed
  42. Taubert D, Roesen R, Schomig E. Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med 2007;167:626-34. PubMed
  43. Taubert D, Roesen R, Lehmann C, et al. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA 2007;298:49-60. PubMed
  44. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8. PubMed
  45. Flammer AJ, Hermann F, Sudano I, et al. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation 2007;116:2376-82. PubMed
  46. Hooper L, Kay C, Abdelhamid A, et al. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr 2012;95:740-51. PubMed
  47. Desideri G, Kwik-Uribe C, Grassi D, et al. Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: the Cocoa, Cognition, and Aging (CoCoA) study. Hyperte PubMed
  48. Shet, M. S., McPhaul, M., Fisher, C. W., Stallings, N. R., and Estabrook, R. W. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997;25(11):1298-1303.
  49. Kot, M. and Daniel, W. A. Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes. Pharmacol Rep. 2009;61(6):1216-1220. PubMed
  50. Gasior, M., Borowicz, K., Buszewicz, G., Kleinrok, Z., and Czuczwar, S. J. Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia 1996;37(3 PubMed
  51. Jankiewicz, K., Chroscinska-Krawczyk, M., Blaszczyk, B., and Czuczwar, S. J. [Caffeine and antiepileptic drugs: experimental and clinical data]. Przegl.Lek. 2007;64(11):965-967.
  52. Chroscinska-Krawczyk, M., Jargiello-Baszak, M., Walek, M., Tylus, B., and Czuczwar, S. J. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol.Rep. 2011;63(1):12-18. PubMed
  53. Mohiuddin, M., Azam, A. T., Amran, M. S., and Hossain, M. A. In vive effects of gliclazide and metformin on the plasma concentration of caffeine in healthy rats. Pak.J Biol Sci 5-1-2009;12(9):734-737.
  54. Mays, D. C., Camisa, C., Cheney, P., Pacula, C. M., Nawoot, S., and Gerber, N. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin.Pharmacol.Ther. 1987;42(6):621-626. PubMed
  55. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  56. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.
  57. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  58. Wang, X. and Yeung, J. H. Effects of the aqueous extract from Salvia miltiorrhiza Bunge on caffeine pharmacokinetics and liver microsomal CYP1A2 activity in humans and rats. J Pharm Pharmacol 2010;62(8):1077-1083.
  59. Zubair, M. H., Zubair, M. H., Zubair, M. N., Zubair, M. M., Aftab, T., and Asad, F. Augmentation of anti-platelet effects of aspirin. J Pak Med.Assoc. 2011;61(3):304-307.
  60. Kot M, Daniel WA. Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep 2008;60:789-97.
  61. Kjaerstad MB, Nielsen F, Nohr-Jensen L, et al. Systemic uptake of miconazole during vaginal suppository use and effect on CYP1A2 and CYP3A4 associated enzyme activities in women. Eur J Clin Pharmacol 2010;66:1189-97. PubMed
  62. Goh BC, Reddy NJ, Dandamudi UB, et al. An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid t
  63. Chen Y, Kang Z, Yan J, et al. Liu wei di huang wan, a well-known traditional Chinese medicine induces CYP1A2 while suppressing CYP2A6 and N-acetyltransferase 2 acivities in man. J Ethnopharmacol 2010;132:213-8.
  64. Suzuki S, Murayama Y, Sugiyama E, et al. Estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, based on physiological liver development and serum protein levels. Yakugaku Zasshi 2010;130:613-20. PubMed
  65. Chien CF, Wu YT, Lee WC, et al. Herb-drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats. Chem Biol Interact 2010;184:458-65. PubMed
  66. Mills BM, Zaya MJ, Walters RR, et al. Current cytochrome P450 phenotyping methods applied to metabolic drug -drug interaction prediction in dogs. Drug Metab Dispos 2010;38:396-404. PubMed
  67. Turpault S, Brian W, Van Horn R, et al. Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6, and 3A. Br J Clin Pharmacol 2009;68:928-35. PubMed
  68. Filimonova AA, Ziganshina LE, Ziganshin AU, Chichirov AA. On the possibility of patient phenotyping on the basis of cytochrome p-450 1A2 isoenzyme activity using caffeine as the test substrate. Eksp Klin Farmakol 2009;72:61-5.
  69. Jenkins J, Williams D, Deng Y, et al. Eltrombopag, an oral thrombopoietin receptor agonist, has no impact on the pharmacokinetic profile of probe drugs for cytochrome P450 isoenzymes CYP3A4, CYP1A2, CYP2C9 and CYP2C19 in healthy men: a cocktail analysis.
  70. Smits, P., Temme, L., and Thien, T. The cardiovascular interaction between caffeine and nicotine in humans. Clin Pharmacol Ther 1993;54(2):194-204. PubMed
  71. Chroscinska-Krawczyk, M., Ratnaraj, N., Patsalos, P. N., and Czuczwar, S. J. Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep. 2009;61(5):819 PubMed
  72. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  73. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  74. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  75. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  76. Perera, V., Gross, A. S., and McLachlan, A. J. Caffeine and paraxanthine HPLC assay for CYP1A2 phenotype assessment using saliva and plasma. Biomed.Chromatogr. 2010;24(10):1136-1144. PubMed
  77. Lee, A. and Storey, D. M. Comparative gastrointestinal tolerance of sucrose, lactitol, or D-tagatose in chocolate. Regul.Toxicol.Pharmacol. 1999;29(2 Pt 2):S78-S82.
  78. Rein, D., Paglieroni, T. G., Wun, T., Pearson, D. A., Schmitz, H. H., Gosselin, R., and Keen, C. L. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000;72(1):30-35. PubMed
  79. Todd, S., Corsnitz, D., Ray, S., and Nassar, J. Outpatient laparoscopic Nissen fundoplication. AORN J 2002;75(5):956, 959-4. PubMed
  80. Pearson, D. A., Paglieroni, T. G., Rein, D., Wun, T., Schramm, D. D., Wang, J. F., Holt, R. R., Gosselin, R., Schmitz, H. H., and Keen, C. L. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb.Res 5-15-2002;106(4-5):191-1 PubMed
  81. Murphy, K. J., Chronopoulos, A. K., Singh, I., Francis, M. A., Moriarty, H., Pike, M. J., Turner, A. H., Mann, N. J., and Sinclair, A. J. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am J Clin Nutr 2 PubMed
  82. Innes, A. J., Kennedy, G., McLaren, M., Bancroft, A. J., and Belch, J. J. Dark chocolate inhibits platelet aggregation in healthy volunteers. Platelets. 2003;14(5):325-327. PubMed
  83. Castell, D. O., Murray, J. A., Tutuian, R., Orlando, R. C., and Arnold, R. Review article: the pathophysiology of gastro-oesophageal reflux disease - oesophageal manifestations. Aliment.Pharmacol.Ther. 2004;20 Suppl 9:14-25. PubMed
  84. Zumbe, A. and Brinkworth, R. A. Comparative studies of gastrointestinal tolerance and acceptability of milk chocolate containing either sucrose, isomalt or sorbitol in healthy consumers and type II diabetics. Z.Ernahrungswiss. 1992;31(1):40-48. PubMed
  85. Hermann, F., Spieker, L. E., Ruschitzka, F., Sudano, I., Hermann, M., Binggeli, C., Luscher, T. F., Riesen, W., Noll, G., and Corti, R. Dark chocolate improves endothelial and platelet function. Heart 2006;92(1):119-120.
  86. Kaltenbach, T., Crockett, S., and Gerson, L. B. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch.Intern.Med 5-8-2006;166(9):965-971. PubMed
  87. Heptinstall, S., May, J., Fox, S., Kwik-Uribe, C., and Zhao, L. Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc.Pharmacol. 2006;47 Suppl 2:S197-S205. PubMed
  88. Feldens, C. A., Vitolo, M. R., and Drachler, Mde L. A randomized trial of the effectiveness of home visits in preventing early childhood caries. Community Dent Oral Epidemiol 2007;35(3):215-223. PubMed
  89. Kannayiram, A., Rezaie, A., and Hadi, S. Chocolate-induced prolonged angiooedema in an elderly patient. Age Ageing 2008;37(4):479-480. PubMed
  90. Hooper, L., Kroon, P. A., Rimm, E. B., Cohn, J. S., Harvey, I., Le Cornu, K. A., Ryder, J. J., Hall, W. L., and Cassidy, A. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2008;88 PubMed
  91. Hamed, M. S., Gambert, S., Bliden, K. P., Bailon, O., Singla, A., Antonino, M. J., Hamed, F., Tantry, U. S., and Gurbel, P. A. Dark chocolate effect on platelet activity, C-reactive protein and lipid profile: a pilot study. South.Med J 2008;101(12):1203- PubMed
  92. Patane, S., Marte, F., La Rosa, F. C., and Rocca, R. L. Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse. Int J Cardiol. 1-24-2009; PubMed
  93. Ried, K., Frank, O. R., and Stocks, N. P. Dark chocolate or tomato extract for prehypertension: a randomised controlled trial. BMC.Complement Altern.Med. 2009;9:22. PubMed
  94. Desch, S., Schmidt, J., Kobler, D., Sonnabend, M., Eitel, I., Sareban, M., Rahimi, K., Schuler, G., and Thiele, H. Effect of cocoa products on blood pressure: systematic review and meta-analysis. Am J Hypertens. 2010;23(1):97-103. PubMed
  95. Davison, K., Berry, N. M., Misan, G., Coates, A. M., Buckley, J. D., and Howe, P. R. Dose-related effects of flavanol-rich cocoa on blood pressure. J Hum Hypertens. 2010;24(9):568-576. PubMed
  96. Desch, S., Kobler, D., Schmidt, J., Sonnabend, M., Adams, V., Sareban, M., Eitel, I., Bluher, M., Schuler, G., and Thiele, H. Low vs. higher-dose dark chocolate and blood pressure in cardiovascular high-risk patients. Am J Hypertens. 2010;23(6):694-700. PubMed
  97. Ried, K., Sullivan, T., Fakler, P., Frank, O. R., and Stocks, N. P. Does chocolate reduce blood pressure? A meta-analysis. BMC.Med 2010;8:39. PubMed
  98. van den Bogaard, B., Draijer, R., Westerhof, B. E., van den Meiracker, A. H., van Montfrans, G. A., and van den Born, B. J. Effects on Peripheral and Central Blood Pressure of Cocoa With Natural or High-Dose Theobromine. A Randomized, Double-Blind Crosso DOI
  99. Persson, I. A., Persson, K., Hagg, S., and Andersson, R. G. Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers--a nutrigenomics perspective. J Cardiovasc.Pharmac PubMed
  100. Khan, N., Monagas, M., Andres-Lacueva, C., Casas, R., Urpi-Sarda, M., Lamuela-Raventos, R. M., and Estruch, R. Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascu
  101. Listl, S. Family composition and children's dental health behavior: evidence from Germany. J Public Health Dent. 2011;71(2):91-101. PubMed
  102. Shrime, M. G., Bauer, S. R., McDonald, A. C., Chowdhury, N. H., Coltart, C. E., and Ding, E. L. Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies. J Nutr 2011;141(11):1982-1988. PubMed
  103. Sudarma, V., Sukmaniah, S., and Siregar, P. Effect of dark chocolate on nitric oxide serum levels and blood pressure in prehypertension subjects. Acta Med.Indones. 2011;43(4):224-228.
  104. Flammer, A. J., Sudano, I., Wolfrum, M., Thomas, R., Enseleit, F., Periat, D., Kaiser, P., Hirt, A., Hermann, M., Serafini, M., Leveques, A., Luscher, T. F., Ruschitzka, F., Noll, G., and Corti, R. Cardiovascular effects of flavanol-rich chocolate in pat
  105. Wolz, M., Schleiffer, C., Klingelhofer, L., Schneider, C., Proft, F., Schwanebeck, U., Reichmann, H., Riederer, P., and Storch, A. Comparison of chocolate to cacao-free white chocolate in Parkinson's disease: a single-dose, investigator-blinded, placebo-
  106. Ried, K., Sullivan, T. R., Fakler, P., Frank, O. R., and Stocks, N. P. Effect of cocoa on blood pressure. Cochrane.Database.Syst.Rev. 2012;8:CD008893. PubMed
  107. Rossner, S. Chocolate--divine food, fattening junk or nutritious supplementation? Eur.J Clin.Nutr. 1997;51(6):341-345. PubMed
  108. Storey, D. M., Koutsou, G. A., Lee, A., Zumbe, A., Olivier, P., Le Bot, Y., and Flourie, B. Tolerance and breath hydrogen excretion following ingestion of maltitol incorporated at two levels into milk chocolate consumed by healthy young adults with and w
  109. Izzo, A. A. and Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009;69(13):1777-1798. PubMed
  110. Ottaviani JI, Balz M, Kimball J, et al. Safety and efficacy of cocoa fl avanol intake in healthy adults: a randomized, controlled, double-masked trial. Am J Clin Nutr 2015;102(6):1425-35.
  111. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648. PubMed
  112. United States Department of Agriculture Research Service. National Nutrient Database for Standard Reference. Basic Report: 19165, Cocoa, dry powder, unsweetened. https://ndb.nal.usda.gov/ndb/foods/show/19165. Updated April 2018. Accessed September 16, 20
  113. Jafarnejad S, Salek M, Clark CCT. Cocoa consumption and blood pressure in middle-aged and elderly subjects: a meta-analysis. Curr Hypertens Rep. 2020;22(1):1. PubMed
  114. Balayssac-Siransy E, Ouattara S, Boka KJM, et al. Dose-effect relation between regular consumption of 100% cocoa powder and blood pressure in young, healthy black Africans. Physiol Rep 2021;9(20):e15070. PubMed
  115. Gleason JL, Sundaram R, Mitro SD, et al. Association of maternal caffeine consumption during pregnancy with child growth. JAMA Netw Open. 2022;5(10):e2239609. PubMed
  116. Devi P, Bajala V, Garg VK, Mor S, Ravindra K. Heavy metal content in various types of candies and their daily dietary intake by children. Environ Monit Assess. 2016;188(2):86. PubMed
  117. Abt E, Robin LP. Perspective on cadmium and lead in cocoa and chocolate. J Agric Food Chem. 2020;68(46):13008-13015. PubMed
  118. Consumer Reports. Lead and cadmium could be in your dark chocolate. December 2022. Available at: https://www.consumerreports.org/health/food-safety/lead-and-cadmium-in-dark-chocolate-a8480295550/. Accessed February 1, 2023.
  119. Seecheran NA, Sukha D, Grimaldos K, et al. Effect of cocoa (Theobroma cacao L.) on platelet function testing profiles in patients with coronary artery disease: ECLAIR pilot study. Open Heart 2022;9(2):e002066.

See these in context on the Cocoa monograph →

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

See these in context on the Ginkgo monograph →

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

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

© 2021 Therapeutic Research Center, LLC

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