Major interaction on record — check this product against your medications before combining. Based on 7 of 8 ingredients. Check your meds →
Dietary supplement

Fat Free Ingredients & Drug Interactions

by Applied Nutriceuticals

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

First and foremost: checking Fat Free 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

Fat Free is a dietary supplement by Applied Nutriceuticals with 8 active ingredients. Its ingredients are commonly taken for heart and blood vessel health, high blood pressure, high cholesterol.Based on those ingredients, 1,502 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Tea, Black Pepper, Rauwolfia serpentina. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Fat Free by Applied Nutriceuticals

Ask about any prescription or over-the-counter medication and we check it for interactions with Fat Free by Applied Nutriceuticals — and tell you which ingredient is responsible.

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Computed from our clinical databases

HelloPharmacist Scorecard of Fat Free by Applied Nutriceuticals

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

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

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

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

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

Why this rating?
  • The label discloses an exact amount for 0 of its 8 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (995.80 mg) without saying how much of each component you get.
Known Interaction Concern
Major identified

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

Why this rating?
  • 6 of the 7 matched ingredients can interact with medications — Indian Snakeroot, Black Pepper, Cocoa, Green Tea, Coffee, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,503 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.
Safety Information
Well characterized

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

Why this rating?
  • We hold adverse-effect (side-effect) data for 7 of the 7 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 6 of 7.
  • General safety write-ups exist for 7 of 7.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

HelloPharmacist summaryFormula with limited ingredient disclosure with no assessable stated purpose. Major medication interactions have been identified, and safety information is well characterized.

Assessment coverage: 7 of 8 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Oct 22, 2015.

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 Fat Free, straight from the product label.

Brand Applied Nutriceuticals
Barcode (UPC) 736211790071
Net contents 90 Capsule(s)
Market status Off market
Date entered into DSLD Oct 22, 2015
DSLD ID 51606
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Fat Free by Applied Nutriceuticals, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
45
UPC/BARCODE
736211790071
IngredientAmount% DV
Theobromine----
Proprietary Blend995.8 mg--
7-Keto DHEA----
Hordenine HCl----
Green Coffee Blend----
Green Tea----
Loquat----
Black Pepper----
Rauwolfia serpentina----

Other ingredients: Gelatin, Silica Dioxide, Magnesium Stearate, Titanium Dioxide, FD&C Yellow #5, FD&C Yellow #6

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.
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

Warning: Do not use if pregnant, nursing, or under the age of 18.

Keep out of the reach of children.

Consult with a health care practitioner before taking this or any dietary supplement, especially if you have or suspect you may have a medical condition, or are taking ANY medications, over the counter products, or other dietary supplements.

Before beginning any weight loss program, consult your health care provider.

Suggested/Recommended/Usage/Directions

Immediately discontinue use and call your health care provider if you experience any adverse reaction.

Directions: For best results take 1-2 capsules in the morning on an empty stomach with 8-12 oz. of fluid. An additional serving can be added in the early afternoon if desired.

Do not exceed recommended serving.

Do not consume with any other stimulants including caffeine.

Do not use if inner safety seal is broken or missing.

Formula

This product contains approximately 105 mg of caffeine per capsule, and may not be appropriate for caffeine-sensitive individuals.

Storage

Store at room temperature and avoid excessive heat.

Seals/Symbols

an Applied Nutraceuticals

Now with 7-Keto

Innovation Series

Brand IP Statement(s)

Better results through science

** 7-Keto is a registered trademark of Humanetics Inc. and holds U.S. Patent #7, 199, 116

General Statements

Potent Daytime Matabolic Booster

Burn Fat - Thermo

FDA Statement of Identity

Dietary Supplement

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

See for yourself

Fat Free by Applied Nutriceuticals label

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

Fat Free 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 Fat Free by Applied Nutriceuticals

These are the 8 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container45 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.

Proprietary Blend

995.8 mg per serving

Other (inactive) ingredients: Gelatin, Silica Dioxide, Magnesium Stearate, Titanium Dioxide, FD&C Yellow #5, FD&C Yellow #6. These complete the product’s ingredient list but are not active constituents.

Interaction report

Fat Free by Applied Nutriceuticals Drug Interactions

Fat Free contains 8 ingredients, and 6 of them have known drug interactions. Altogether they interact with 1,502 medications. Here’s the picture, then you can look up your own drug.

Want to check YOUR meds against Fat Free?

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
1,502Drugs
94 Major 1,400 Moderate 8 Minor

Ingredients driving the most interactions

Green Tea 1,293
Black Pepper 1,019
Rauwolfia serpentina 843
Theobromine 661
Green Coffee Blend 591

Individual Drug Interactions

The ingredients in Fat Free interact with 1,502 drugs. Click any drug to see the details.

6 of the 8 ingredients in Fat Free interact with drugs. Each result below shows which ingredient is responsible. Green Tea Black Pepper Rauwolfia serpentina Theobromine Green Coffee Blend Hordenine HCl

Each ingredient & the kinds of drugs it affects

For each ingredient in Fat Free 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 Tea58 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 full monograph & all 58 interactions

Black Pepper17 drug types · 1,019 drugs

Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Antidiabetes Drugs

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

Likelihood Possible Evidence D
Atorvastatin (Lipitor)

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

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

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

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

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

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

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

Likelihood Possible Evidence D
Lithium

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

Likelihood Probable Evidence D
Nevirapine (Viramune)

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

Likelihood Probable Evidence D
P-Glycoprotein Substrates

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

Likelihood Possible Evidence D
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence D
Phenytoin (Dilantin)

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

Likelihood Possible Evidence B
Propranolol (Inderal)

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

Likelihood Possible Evidence B
Rifampin (Rifadin)

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

Likelihood Possible Evidence B
Theophylline

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

Likelihood Possible Evidence D
Amoxicillin (Amoxil, Trimox)

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

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

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

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

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

Likelihood Possible Evidence D
Black Pepper full monograph & interactions

Rauwolfia serpentina13 drug types · 843 drugs

Antipsychotic Drugs

Theoretically, concomitant use might increase the risk of adverse effects.
Concomitant use of neuroleptics with Indian snakeroot may potentiate the effects of these drugs, as well as the alkaloid constituents of Indian snakeroot.

Likelihood Probable Evidence D
Beta-Blockers

Theoretically, taking Indian snakeroot with beta-blockers might increase the risk of bradycardia and/or hypotension.
Indian snakeroot contains small amounts of reserpine. Reserpine causes catecholamine-depletion. Concomitant use of Indian snakeroot and beta-blockers might increase the risk or bradycardia and/or hypotension.

Likelihood Probable Evidence D
Digoxin (Lanoxin)

Theoretically, taking Indian snakeroot with digoxin might increase the risk of bradycardia.
Bradycardia has been reported in clinical trials using Indian snakeroot. Concomitant use of digoxin with Indian snakeroot might potentiate this effect.

Likelihood Probable Evidence D
Levodopa

Theoretically, taking Indian snakeroot with levodopa may reduce the effectiveness of levodopa.
Extrapyramidal motor symptoms and Parkinson-like symptoms have been reported in clinical trials using Indian snakeroot. Concomitant use of Indian snakeroot with levodopa may reduce the effectiveness of levodopa and increase extrapyramidal motor symptoms.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, taking Indian snakeroot might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Indian snakeroot contains small amounts of the drug yohimbine. In vitro research shows that yohimbine inhibits platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, concomitant use of Indian snakeroot with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research shows that Indian snakeroot lowers blood glucose levels. This effect has not been reported in humans.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, concomitant use of Indian snakeroot and antihypertensive drugs might increase the risk of hypotension.
Indian snakeroot, which contains reserpine, can reduce both systolic and diastolic blood pressure.

Likelihood Possible Evidence B
Cns Depressants

Theoretically, taking Indian snakeroot might cause additive sedative effects.
Sedation and drowsiness have been reported in clinical trials using Indian snakeroot.

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

Theoretically, Indian snakeroot might inhibit CYP2D6 enzymes and reduce the metabolism of CYP2D6 substrates.
Indian snakeroot contains small amounts of the drug yohimbine. In vitro research shows that yohimbine inhibits CYP2D6 enzyme activity.

Likelihood Possible Evidence D
Ephedrine

Theoretically, taking Indian snakeroot with ephedrine might alter the effects and side effects of ephedrine.
Indian snakeroot contains small amounts of reserpine. Reserpine reduces indirect sympathomimetic drug activity. However, another constituent of Indian snakeroot, yohimbine, has stimulant activity and may increase the risk of adverse effects with ephedrine.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking Indian snakeroot with MAOIs might cause additive effects.
Yohimbine, a constituent of Indian snakeroot, has MAO inhibitory effects. At high doses, yohimbine is a non-selective inhibitor of MAO.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, concomitant use might cause additive effects.
Yohimbine, a constituent of Indian snakeroot, has sympathomimetic effects and increases blood pressure in a dose-dependent manner. Theoretically, taking Indian snakeroot with stimulant drugs can have additive stimulant and hypertensive effects.

Likelihood Possible Evidence D
Tricyclic Antidepressants (Tcas)

Theoretically, concomitant use might alter the effects of Indian snakeroot and increase the risk of adverse effects.
A small clinical study in patients taking TCAs for at least 4 weeks shows that receiving doses of intravenous yohimbine, a constituent of Indian snakeroot, 2.5-20 mg daily for up to 7 days precipitates severe anxiety, agitation, and tremor. Also, concomitant use of TCAs with Indian snakeroot may decrease the effects of other rauwolfia alkaloids.

Likelihood Possible Evidence D
Rauwolfia serpentina full monograph & interactions

Theobromine37 drug types · 661 drugs

Ace Inhibitors (Aceis)

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

Likelihood Possible Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Alcohol (Ethanol)

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Antihypertensive Drugs

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

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

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

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

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

Likelihood Possible Evidence D
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Ephedrine

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Flutamide (Eulexin)

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

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

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

Likelihood Possible Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenylpropanolamine

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

Likelihood Probable Evidence B
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Stimulant Drugs

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

Likelihood Probable Evidence C
Theophylline

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

Likelihood Probable Evidence B
Theobromine full monograph & all 37 interactions

Green Coffee Blend33 drug types · 591 drugs

Ephedrine

Theoretically, concomitant use might increase the risk of stimulant adverse effects.
Coffee 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. Tell patients to avoid taking caffeine with ephedrine and other stimulants.

Likelihood Probable Evidence D
Adenosine (Adenocard)

Theoretically, coffee might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Coffee 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 such as caffeine, as well as 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
Alendronate (Fosamax)

Coffee reduces alendronate bioavailability.
Separate coffee ingestion and alendronate administration by two hours. Coffee reduces alendronate bioavailability by 60%.

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Coffee contains caffeine. Caffeine is reported to have antiplatelet activity. Theoretically, the caffeine in coffee might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood.

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

Theoretically, concomitant use of large amounts of coffee might increase cardiac inotropic effects of beta-agonists.
Coffee contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Cimetidine (Tagamet)

Theoretically, cimetidine might increase the effects and adverse effects of caffeine in coffee.
Coffee contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Theoretically, coffee might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Coffee contains caffeine. 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 coffee.
Coffee contains caffeine. Oral contraceptive drugs can decrease caffeine clearance by 40% to 65%.

Likelihood Probable Evidence B
Dipyridamole (Persantine)

Theoretically, coffee might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Coffee contains caffeine. Caffeine is a methylxyanthine that may inhibit dipyridamole-induced vasodilation. It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as coffee, 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.
Coffee contains caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine.

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, concomitant use might increase the risk of hypokalemia.
Coffee contains caffeine. Caffeine, especially in excessive amounts, 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.
Coffee contains caffeine. Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence B
Lamotrigine (Lamictal)

Coffee consumption can decrease the levels and clinical effects of lamotrigine.
A pharmacokinetic study in patients taking lamotrigine shows that consumption of coffee, both caffeinated and decaffeinated, can decrease the area under the concentration-time curve (AUC) and the peak plasma level (Cmax) of lamotrigine. Each additional cup of coffee reduced the AUC and Cmax by 4% and 3%, respectively. It is unclear whether this interaction is due to induction of lamotrigine metabolism or inhibition of lamotrigine absorption.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Coffee can reduce the absorption of levothyroxine.
In some patients, coffee can reduce levothyroxine absorption, possibly through the formation of non-absorbable complexes. A pharmacokinetic study in these patients found that 25-30 mL of espresso coffee consumed with levothyroxine tablets delayed the time to peak plasma levels by 38-43 minutes, reduced the peak plasma level (Cmax) by 19% to 36%, and reduced the area under the curve (AUC) by 27% to 36%. Coffee consumed one hour after levothyroxine did not affect absorption. It is not known whether this interaction occurs with other types of coffee. Tell patients to avoid drinking coffee at the same time that they take their levothyroxine, and for up to an hour afterwards.

Likelihood Possible Evidence B
Lithium

Theoretically, abrupt coffee withdrawal might increase the levels and adverse effects of lithium.
Coffee contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels. Two cases of lithium tremor that worsened with abrupt coffee withdrawal have been reported. There is also one case of a 2.8-fold increase in blood lithium levels after a patient taking lithium reduced his coffee consumption from 13-20 cups daily to 10 cups daily.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Coffee contains caffeine. Caffeine has been shown to inhibit monoamine oxidase (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.
Coffee 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, coffee might reduce the effects of pentobarbital.
Coffee contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenylpropanolamine

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Coffee 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
Pioglitazone (Actos)

Theoretically, coffee might increase the levels and clinical effects of pioglitazone.
Coffee 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
Quinolone Antibiotics

Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Coffee contains caffeine. Concomitant use of caffeine and quinolones can decrease caffeine clearance and increase effects and risk of adverse effects.

Likelihood Probable Evidence B
Riluzole (Rilutek)

Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Coffee contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), 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.
Coffee 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 Probable Evidence C
Theophylline

Theoretically, coffee might increase the levels and adverse effects of theophylline.
Coffee contains caffeine, which can increase theophylline levels.

Likelihood Probable Evidence B
Green Coffee Blend full monograph & all 33 interactions

Hordenine HCl3 drug types · 329 drugs

Monoamine Oxidase Inhibitors (Maois)

Hordenine is structurally similar to tyramine In vitro research shows that hordenine is a selective substrate for monoamine oxidase-B in the liver. Theoretically, concomitant use of hordenine with MAOIs might increase blood pressure, potentially leading to a hypertensive crisis.
Some MAOIs include isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate).

Likelihood Possible Evidence D
Stimulant Drugs

Hordenine is structurally similar to N-methyltyramine and synephrine, constituents in bitter orange known to have stimulant properties. Theoretically, taking hordenine with drugs with stimulant properties might increase the risk of hypertension and other adverse cardiovascular effects.
Some of these drugs include amphetamine, caffeine, methylphenidate, pseudoephedrine, and many others.

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

Hordenine weakly inhibits cytochrome P450 2D6 (CYP2D6) enzymes in vitro. Theoretically, hordenine might increase the levels of CYP2D6 substrates.
Some of drugs that are CYP2D6 substrates include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and others.

Likelihood Possible Evidence D
Hordenine HCl full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Fat Free, from the product label.

Applied Nutriceuticals

See all Applied Nutriceuticals products
Name
Applied Nutriceuticals
Street Address
8112 Statesville Rd Suite G
City
Charlotte
State
NC
ZipCode
28269
Phone Number
704-509-5999
Web Address
www.appnut.com
Pharmacist Counseling Corner

Fat Free by Applied Nutriceuticals: Common Questions

Does Fat Free by Applied Nutriceuticals interact with any medications?
Yes. Based on its ingredients, Fat Free has a known interaction with 1,502 medications, including 94 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Fat Free contains 8 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.

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

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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.

Fat Free label
Go deeper

The Full Monographs Behind Fat Free’s Ingredients

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

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

7-keto-dhea

7-keto-DHEA is a lab-made metabolite of the hormone DHEA that is marketed mainly for weight loss and a faster metabolism. Unlike DHEA, it is not thought to convert into estrogen or testoster...

Read the full 7-keto-dhea monograph → Herb & supplement monograph

Hordenine

Interacts with 329 drugs

Hordenine is a natural alkaloid found in barley and some cacti that is marketed as a stimulant for energy, focus, and fat loss, but solid human evidence for these benefits is lacking. Its sa...

Read the full Hordenine monograph → Herb & supplement monograph

Coffee

Interacts with 591 drugs

Coffee is a widely consumed beverage made from roasted coffee beans, valued mainly for its caffeine, which boosts alertness and energy. For most healthy adults, moderate coffee intake is gen...

Read the full Coffee 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

Black Pepper

Interacts with 1,019 drugs

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

Read the full Black Pepper monograph → Herb & supplement monograph

Indian Snakeroot

Interacts with 843 drugs

Indian snakeroot is a traditional Ayurvedic plant that contains reserpine, a compound with real blood-pressure-lowering and sedative effects. Because its potent alkaloids can cause serious s...

Read the full Indian Snakeroot monograph →
Sources

Sources & How We Checked

Fat Free'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 590 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.

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 →

7-keto-dhea 2 references
  1. Davidson M, Marwah A, Sawchuk RJ, et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med 2000;23:300-10..
  2. Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem 2007;18(9):629-34. PubMed

See these in context on the 7-keto-dhea monograph →

Hordenine 3 references
  1. Barwell CJ, Basma AN, Lafi MA, Leake LD. Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat. J Pharm Pharmacol 1989;41(6):421-3. PubMed
  2. Nelson BC, Putzbach K, Sharpless KE, Sander LC. Mass spectrometric determination of the predominant adrenergic protoalkaloids in bitter orange (Citrus aurantium). J Agric Food Chem 2007;55(24):9769-75. PubMed
  3. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. PubMed

See these in context on the Hordenine monograph →

Coffee 175 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. Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricylic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984;73:1056-8. PubMed
  8. Kulhanek F, Linde OK, Meisenberg G. Precipitation of antipsychotic drugs in interaction with coffee or tea. Lancet 1979;2:1130.
  9. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  10. 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.
  11. Grubben MJ, Boers GH, Blom HJ, et al. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. Am J Clin Nutr 2000;71:480-4. PubMed
  12. 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
  13. 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
  14. 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
  15. 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.
  16. 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
  17. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  18. 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
  19. 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
  20. 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
  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. Margolin KA, Green MR. Polymicrobial enteric septicemia from coffee enemas. West J Med 1984;140:460.
  24. Urgert R, Vliet TV, Zock PL, et al. Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers. Am J Clin Nutr 2000;72:1107-10. PubMed
  25. Green S. A critique of the rationale for cancer treatment with coffee enemas and diet. JAMA 1992;268:3224-7. DOI
  26. Shils ME, Herman MG. Unproved dietary claims in the treatment of patients with cancer. Bull N Y Acad Med 1982;58:323-39.
  27. 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
  28. Bak AA, Grobbee DE. The effect of serum cholesterol levels of coffee brewed by filtering or boiling. N Engl J Med 1989;321:1432-7.
  29. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  30. 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
  31. 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
  32. 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
  33. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  34. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  35. Heliovaara M, Aho K, Knekt P, et al. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann Rheum Dis 2000;59:631-5. PubMed
  36. 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
  37. Brown BT. Treating cancer with coffee enemas and diet. JAMA 1993;269:1635-6. DOI
  38. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  39. 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
  40. Samarrae WA, Truswell AS. Short-term effect of coffee on blood fibrinolytic activity in healthy adults. Atherosclerosis 1977;26:255-60. PubMed
  41. Klag MJ, Wang NY, Meoni LA, et al. Coffee intake and risk of hypertension: The John Hopkins precursors study. Arch Intern Med 2002;162:657-62. DOI
  42. Brenner H, Rothenbacher D, Bode G, Adler G. Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study. BMJ 1997;315:1489-92.
  43. Jee SH, He J, Appel LJ, et al. Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 2001:153:353-62. PubMed
  44. Michaud DS, Giovannucci E, Willett WC, et al. Coffee and alcohol consumption and risk of pancreatic cancer in two prospective United States cohorts. Cancer Epidemiol Biomarkers Prev 2001;10:429-37.
  45. Tavani A, Pregnolato A, La Vecchia C, et al. Coffee consumption and the risk of breast cancer. Eur J Cancer Prev 1998;7:77-82.
  46. Tavani A, La Vecchia C. Coffee and cancer: a review of epidemiological studies, 1990-1999. Eur J Cancer Prev 2000;9:241-56.
  47. Hartman TJ, Tangrea JA, Pietinen P, et al. Tea and coffee consumption and risk of colon and rectal cancer in middle-aged Finnish men. Nutr Cancer 1998;31:41-8. PubMed
  48. Anon. Filtering the news about coffee. University of California, Berkeley Wellness Letter 2001:17:1-2.
  49. 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
  50. Jacobsen BK, Heuch I. Coffee, K-ras mutations and pancreatic cancer: a heterogeneous aetiology or an artefact? J Epidemiol Community Health 2000;54:654-5.
  51. Porta M, Malats N, Alguacil J, et al. Coffee, pancreatic cancer, and K-ras mutations: updating the research agenda. J Epidemiol Community Health 2000;54:656-9.
  52. Kuper HE, Mucci LA, Trichopoulos D. Coffee, pancreatic cancer, and the question of causation. J Epidemiol Community Health 2000;54:650-1.
  53. Urgert R, Meyboom S, Kuilman M, et al. Comparison of effect of cafetiere and filtered coffee on serum concentrations of liver aminotransferases and lipids: six month randomised controlled trial. BMJ 1996;313:1362-6.. DOI
  54. 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
  55. 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
  56. 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
  57. Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003;289:1537-45.. PubMed
  58. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  59. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  60. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  61. Wisborg K, Kesmodel U, Bech BH, et al. Maternal consumption of coffee during pregnancy and stillbirth and infant death in first year of life: prospective study. BMJ 2003;326:420.. PubMed
  62. 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
  63. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  64. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  65. Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J Nutr 2003;133:3228-32. PubMed
  66. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  67. Food and Nutrition Board, Institute of Medicine. Nutrition during lactation. Washington, DC: National Academy Press, 1991. Available at: http://books.nap.edu/books/0309043913/html.
  68. Gertz BJ, Holland SD, Kline WF, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther 1995;58:288-98. PubMed
  69. 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
  70. 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
  71. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  72. 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
  73. 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
  74. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  75. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  76. 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
  77. 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.
  78. 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
  79. Holmgren P, Norden-Pettersson L, Ahlner J. Caffeine fatalities--four case reports. Forensic Sci Int 2004;139:71-3. PubMed
  80. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  81. 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
  82. Sato J, Nakata H, Owada E, et al. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol 1993;44:295-8. PubMed
  83. Baker JA, McCann SE, Reid ME, et al. Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers. Nutr Cancer 2005;52:15-21. PubMed
  84. Benowitz NL, Osterloh J, Goldschlager N, et al. Massive catecholamine release from caffeine poisoning. JAMA 1982;248:1097-8. DOI
  85. Leson CL, McGuigan MA, Bryson SM. Caffeine overdose in an adolescent male. J Toxicol Clin Toxicol 1988;26:407-15. PubMed
  86. 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
  87. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  88. 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
  89. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  90. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  91. Lopez-Garcia E, van Dam RM, Willett WC, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 2006;113:2045-53. PubMed
  92. Baylin A, Hernandez-Diaz S, Kabagambe EK, et al. Transient exposure to coffee as a trigger of a first nonfatal myocardial infarction. Epidemiology 2006;17:506-11. PubMed
  93. 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
  94. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  95. Benvenga S. Bartolone L, Pappalardo MA, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid 2008;18:293-301. PubMed
  96. 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
  97. 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
  98. 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.
  99. 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
  100. Azcona O, Barbanoi MJ, Torrent J, Jane F. Evaluation of the central effects of alcohol and caffeine interaction. Br J Clin Pharmacol 1995;40:393-400. PubMed
  101. Harder S, Staib AH, Beer C, et al. 4-quinolones inhibit biotransformation of caffeine. Eur J Clin Pharmacol 1988;35:651-6. PubMed
  102. Zhang LL, Zhang JR, Guo K, et al. Effects of fluoroquinolones on CYP4501A and 3A in male broilers. Res Vet Sci 2011;90:99-105. PubMed
  103. Cesana M, Broccali G, Imbimbo BP, Crema A. Effect of single doses of rufloxacin on the disposition of theophylline and caffeine after single administration. Int J Clin Pharmacol Ther Toxicol 1991:29:133-8.
  104. Broughton LJ, Rogers HJ. Decreased systemic clearance of caffeine due to cimetidine. Br J Clin Pharmacol 1981;12:155-9. PubMed
  105. Smits P, Straatman C, Pijpers E, Thien T. Dose-dependent inhibition of the hemodynamic response to dipyridamole by caffeine. Clin Pharmacol Ther 1991;50:529-37. PubMed
  106. Zelenitsky SA, Norman A, Nix DE. The effects of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. J Infect Dis Pharmacother 1995;1:1-11.
  107. Joeres R, Richter E. Mexiletine and caffeine elimination. N Engl J Med 1987;317:117. PubMed
  108. Jonkman JH, Sollie FA, Sauter R, Steinijans VW. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther 1991;49:248-55. PubMed
  109. 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
  110. 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
  111. 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
  112. 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
  113. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433. PubMed
  114. 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
  115. 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
  116. 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
  117. 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
  118. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  119. Banko, L. T., Haq, S. A., Rainaldi, D. A., Klem, I., Siegler, J., Fogel, J., Sacchi, T. J., and Heitner, J. F. Incidence of caffeine in serum of patients undergoing dipyridamole myocardial perfusion stress test by an intensive versus routine caffeine his
  120. 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
  121. 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
  122. 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
  123. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  124. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  125. Mostofsky, E., Schlaug, G., Mukamal, K. J., Rosamond, W. D., and Mittleman, M. A. Coffee and acute ischemic stroke onset: the Stroke Onset Study. Neurology 11-2-2010;75(18):1583-1588. PubMed
  126. 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
  127. Li, G. Z., Zhang, N., Du, P., Yang, Y., Wu, S. L., Xiao, Y. X., Jin, R., Liu, L., Shen, H., and Dai, Y. Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms: a Chinese multi-center study. Chin Med
  128. Smits, P., Lenders, J. W., and Thien, T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin.Pharmacol.Ther. 1990;48(4):410-418. PubMed
  129. Rossignol, A. M. and Bonnlander, H. Caffeine-containing beverages, total fluid consumption, and premenstrual syndrome. Am.J.Public Health 1990;80(9):1106-1110. PubMed
  130. Jeppesen, U., Loft, S., Poulsen, H. E., and Brsen, K. A fluvoxamine-caffeine interaction study. Pharmacogenetics 1996;6(3):213-222. PubMed
  131. Smits, P., Corstens, F. H., Aengevaeren, W. R., Wackers, F. J., and Thien, T. False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion. J Nucl.Med. 1991;32(8):1538-1541. DOI
  132. Wang Y, Yu X, Wu Y, Zhang D. Coffee and tea consumption and risk of lung cancer: a dose-response analysis of observational studies. Lung Cancer. 2012;78(2):169-70. PubMed
  133. 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
  134. 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
  135. Chiaffarino F, Bravi F, Cipriani S, Parazzini F, Ricci E, Viganò P, La Vecchia C. Coffee and caffeine intake and risk of endometriosis: a meta-analysis. Eur J Nutr. 2014 Oct;53(7):1573-9. doi: 10.1007/s00394-014-0662-7. Epub 2014 31. PubMed
  136. Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies. Gynecol Oncol. 2013 Jun;129(3):620-9. doi: 10.1016/j.ygyno.2013.03.014. Epub 2013 25. Review. PubMed
  137. Sanikini H, Dik VK, Siersema PD, Bhoo-Pathy N, Uiterwaal CS, Peeters PH, González CA, Zamora-Ros R, Overvad K, Tjønneland A, Roswall N, Boutron-Ruault MC, Fagherazzi G, Racine A, Kühn T, Katzke V, Boeing H, Trichopoulou A, Trichopoulos D, Lagiou P, Palli
  138. 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
  139. 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
  140. Turati F, Galeone C, Talamini R, et al. Coffee, decaffeinated coffee, tea, and pancreatic cancer risk: a pooled-analysis of two Italian case-control studies. Eur J Cancer Prev 2011;20(4):287-92. PubMed
  141. 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
  142. Acosta RD, Cash BD. Clinical effects of colonic cleansing for general health promotion: a systematic review. Am J Gastroenterol. 2009;104(11):2830-6. PubMed
  143. Kunitake Y, Mizoguchi Y, Sogawa R, et al. Effect of excessive coffee consumption on the clinical course of a patient with bipolar disorder: a case report and literature review. Clin Neuropharmacol. 2017 Jul/Aug;40(4):160-162. doi: 10.1097/WNF.00000000 PubMed
  144. Crippa A, Discacciati A, Larsson SC, Wolk A, Orsini N. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am J Epidemiol. 2014 Oct 15;180(8):763-75. doi: 10.1093/aje/kwu194. PubMed
  145. Loftfield E, Cornelis MC, Caporaso N, Yu K, Sinha R, Freedman N. Association of coffee drinking With mortality by genetic variation in caffeine metabolism: findings from the UK biobank. JAMA Intern Med. 2018 Aug 1;178(8):1086-1097. doi: 10.1001/jamaintern PubMed
  146. 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
  147. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  148. 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
  149. Lee AH, Kabashneh S, Tsouvalas CP, et al. Proctocolitis from coffee enema. ACG Case Rep J. 2020;7(1):e00292. PubMed
  150. Tverdal A, Selmer R, Cohen JM, Thelle DS. Coffee consumption and mortality from cardiovascular diseases and total mortality: Does the brewing method matter? Eur J Prev Cardiol. 2020:2047487320914443. PubMed
  151. Yamakawa M, Wada K, Goto Y, et al. Associations between coffee consumption and all-cause and cause-specific mortality in a Japanese city: the Takayama study. Public Health Nutr. 2019;22(14):2561-2568. PubMed
  152. Zhou CD, Kuan AS, Reeves GK, et al. Coffee and pancreatic cancer risk among never-smokers in the UK prospective Million Women Study. Int J Cancer. 2019;145(6):1484-1492. PubMed
  153. Stojanovic E, Scanlan AT, Milanovic Z, Fox JL, Stankovic R, Dalbo VJ. Acute caffeine supplementation improves jumping, sprinting, and change-of-direction performance in basketball players when ingested in the morning but not evening. Eur J Sport Sci. 2021 PubMed
  154. Ruggiero E, Di Castelnuovo A, Costanzo S, et al. Daily coffee drinking is associated with lower risks of cardiovascular and total mortality in a general Italian population: Results from the Moli-sani study. J Nutr. 2020:nxaa365. PubMed
  155. Kim Y, Je Y, Giovannucci E. Coffee consumption and all-cause and cause-specific mortality: a meta-analysis by potential modifiers. Eur J Epidemiol. 2019 Aug;34(8):731-752. doi: 10.1007/s10654-019-00524-3. Epub 2019 May 4. PubMed
  156. Stevens LM, Linstead E, Hall JL, Kao DP. Association between coffee intake and incident heart failure risk: A machine learning analysis of the FHS, the ARIC Study, and the CHS. Circ Heart Fail. 2021:CIRCHEARTFAILURE119006799. PubMed
  157. Ribeiro EM, Alves M, Costa J, Ferreira JJ, Pinto FJ, Caldeira D. Safety of coffee consumption after myocardial infarction: A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis. 2020;30(12):2146-2158. PubMed
  158. Grosso G, Micek A, Godos J, ET AL. Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: a dose-response meta-analysis. Eur J Epidemiol. 2016;31(12):1191-1205. PubMed
  159. Kim EJ, Hoffmann TJ, Nah G, Vittinghoff E, Delling F, Marcus GM. Coffee consumption and incident tachyarrhythmias: Reported behavior, mendelian randomization, and their interactions. JAMA Intern Med. 2021. PubMed
  160. Loftfield E, Freedman ND, Graubard BI, et al. Association of coffee consumption with overall and cause-specific mortality in a large US prospective cohort study. Am J Epidemiol. 2015;182(12):1010-22. PubMed
  161. Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E. The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis. Am J Clin Nutr. 2011;94(4):1113-26. PubMed
  162. Miranda AM, Goulart AC, Benseñor IM, Lotufo PA, Marchioni DM. Moderate coffee consumption is associated with lower risk of mortality in prior Acute Coronary Syndrome patients: a prospective analysis in the ERICO cohort. Int J Food Sci Nutr. 2020:1-11.
  163. Nordestgaard AT, Nordestgaard BG. Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95?000-223?000 individuals. Int J Epidemiol. 2016;45(6):1938-1952. PubMed
  164. Zhang Y, Yang H, Li S, Li WD, Wang Y. Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLoS Med 2021;18(11):e1003830. PubMed
  165. Chan L, Hong CT, Bai CH. Coffee consumption and the risk of cerebrovascular disease: a meta-analysis of prospective cohort studies. BMC Neurol 2021;21(1):380. PubMed
  166. Welty TE, Gidal BE, Duan J, et al. Coffee and cigarette smoking interactions with lamotrigine. Epilepsy Behav 2021;116:107741. PubMed
  167. 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
  168. 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
  169. 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
  170. 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
  171. 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
  172. Han M, Oh Y, Myung SK. Coffee intake and risk of hypertension: A meta-analysis of cohort studies. J Korean Med Sci 2022;37(45):e332. PubMed
  173. Sehrawat O, Mehra NS, Kowlgi NG, et al. Association between coffee consumption and incident atrial fibrillation (from the Multi-Ethnic Study of Atherosclerosis [MESA]). Am J Cardiol 2023;186:5-10. PubMed
  174. Marcus GM, Rosenthal DG, Nah G, et al. Acute effects of coffee consumption on health among ambulatory adults. N Engl J Med. 2023;388(12):1092-1100. PubMed
  175. Abtan J, Ducrocq G, Elbez Y, et al. Association between coffee or tea consumption and cardiovascular outcomes in patients with stable coronary artery disease: Analysis from the CLARIFY registry. Arch Cardiovasc Dis 2023;116(8-9):382-389. PubMed

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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 →

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

See these in context on the Black Pepper monograph →

Indian Snakeroot 43 references
  1. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
  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. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  4. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  5. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  6. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  7. Young DS. Effects of Drugs on Clinical Laboratory Tests 4th ed. Washington: AACC Press, 1995.
  8. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980;60:85-7.
  9. Teloken C, Rhoden EL, Sogari P, et al. Therapeutic effects of high dose yohimbine hydrochloride on organic erectile dysfunction. J Urol 1998;159:122-4. PubMed
  10. Jacobsen FM. Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 1992;53:119-22.
  11. Hollander E, McCarley A. Yohimbine treatment of sexual side effects induced by serotonin reuptake blockers. J Clin Psychiatry 1992;53:207-9.
  12. Sandler B, Aronson P. Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome. Urol 1993;41:343-5. PubMed
  13. Kearney T, Tu N, Haller C. Adverse drug events associated with yohimbine-containing products: a retrospective review of the California Poison Control System reported cases. Ann Pharmacother 2010;44:1022-9. PubMed
  14. VandenBrink, B. M., Foti, R. S., Rock, D. A., Wienkers, L. C., and Wahlstrom, J. L. Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate-dependent inhibition. Drug Metab Dispos. 2012;40(1):47-53. PubMed
  15. Mustonen, P., Savola, J., and Lassila, R. Atipamezole, an imidazoline-type alpha(2)-adrenoceptor inhibitor, binds to human platelets and inhibits their adrenaline-induced aggregation more effectively than yohimbine. Thromb.Res 8-1-2000;99(3):231-237.
  16. Bagheri, H., Schmitt, L., Berlan, M., and Montastruc, J. L. Effect of 3 weeks treatment with yohimbine on salivary secretion in healthy volunteers and in depressed patients treated with tricyclic antidepressants. Br J Clin Pharmacol 1992;34(6):555-558. PubMed
  17. Swann, A. C., Birnbaum, D., Jagar, A. A., Dougherty, D. M., and Moeller, F. G. Acute yohimbine increases laboratory-measured impulsivity in normal subjects. Biol.Psychiatry 5-15-2005;57(10):1209-1211. PubMed
  18. Adeniyi, A. A., Brindley, G. S., Pryor, J. P., and Ralph, D. J. Yohimbine in the treatment of orgasmic dysfunction. Asian J Androl 2007;9(3):403-407. PubMed
  19. Giampreti, A., Lonati, D., Locatelli, C., Rocchi, L., and Campailla, M. T. Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol.(Phila) 2009;47(8):827-829. PubMed
  20. Myers, A. and Barrueto, F., Jr. Refractory priapism associated with ingestion of yohimbe extract. J Med Toxicol. 2009;5(4):223-225.
  21. Berlin, I., Crespo-Laumonnier, B., Cournot, A., Landault, C., Aubin, F., Legrand, J. C., and Puech, A. J. The alpha 2-adrenergic receptor antagonist yohimbine inhibits epinephrine-induced platelet aggregation in healthy subjects. Clin Pharmacol.Ther. 199
  22. Swann, A. C. Mechanisms of impulsivity in bipolar disorder and related illness. Epidemiol.Psichiatr.Soc. 2010;19(2):120-130.
  23. Landis, E. and Shore, E. Yohimbine-induced bronchospasm. Chest 1989;96(6):1424. PubMed
  24. Susset, J. G., Tessier, C. D., Wincze, J., Bansal, S., Malhotra, C., and Schwacha, M. G. Effect of yohimbine hydrochloride on erectile impotence: a double-blind study. J Urol. 1989;141(6):1360-1363. PubMed
  25. Braddock, L., Cowen, P. J., Elliott, J. M., Fraser, S., and Stump, K. Binding of yohimbine and imipramine to platelets in depressive illness. Psychol.Med 1986;16(4):765-773. PubMed
  26. Charney, D. S., Heninger, G. R., and Sternberg, D. E. Assessment of alpha 2 adrenergic autoreceptor function in humans: effects of oral yohimbine. Life Sci 6-7-1982;30(23):2033-2041.
  27. Boon, N. A., Elliott, J. M., Grahame-Smith, D. G., John-Green, T., and Stump, K. A comparison of alpha 2-adrenoreceptor binding characteristics of intact human platelets identified by [3H]-yohimbine and [3H]- dihydroergocryptine. J Auton.Pharmacol 1983;3
  28. Siddiqui, M. A., More-O'Ferrall, D., Hammod, R. S., Baime, R. V., and Staddon, A. P. Agranulocytosis associated with yohimbine use. Arch.Intern.Med 6-10-1996;156(11):1235-1237.
  29. Mann, K., Klingler, T., Noe, S., Roschke, J., Muller, S., and Benkert, O. Effects of yohimbine on sexual experiences and nocturnal penile tumescence and rigidity in erectile dysfunction. Arch.Sex Behav. 1996;25(1):1-16. PubMed
  30. Riley AJ, Goodman R, Kellett JM, and et al. Double blind trial of yohimbine hydrochloride in the treatment of erection inadequacy. Sexual Marital Ther 1989;4(1):17-26. DOI
  31. Ruck B, Shih RD, Marcus SM. Hypertensive crisis from herbal treatment of impotence. Am J Emerg Med. 1999;17:317-318. PubMed
  32. Wylie KR. Yohimbine and sinusitis. Br J Psychiatry. 1996;169(3):384-5. PubMed
  33. Lobay D. Rauwolfia in the Treatment of Hypertension. Integr Med (Encinitas). 2015 Jun;14(3):40-6.
  34. Lowinger P. Rauwolfia serpentina in the control of anxiety. Psychiatr Q. 1957 Jul;31(3):445-53. PubMed
  35. Sheldon MB, Kotte JH. Effect of Rauwolfia serpentina and reserpine on the blood pressure in essential hypertension; a long-term double-blind study. Circulation. 1957 Aug;16(2):200-6.
  36. Vakil RJ. A clinical trial of Rauwolfia serpentina in essential hypertension. Br Heart J. 1949 Oct;11(4):350-5. PubMed
  37. Azmi MB, Qureshi SA. Methanolic Root Extract of Rauwolfia serpentina Benth Improves the Glycemic, Antiatherogenic, and Cardioprotective Indices in Alloxan-Induced Diabetic Mice. Adv Pharmacol Sci. 2012;2012:376429.
  38. Azmi MB, Qureshi SA. Rauwolfia serpentina improves altered glucose and lipid homeostasis in fructose-induced type 2 diabetic mice. Pak J Pharm Sci. 2016 Sep;29(5):1619-1624.
  39. Achor RW, Hanson NO, Gifford RW Jr. Hypertension treated with Rauwolfia serpentina (whole root) and with reserpine; controlled study disclosing occasional severe depression. J Am Med Assoc. 1955 Oct 29;159(9):841-5. PubMed
  40. Wilkins RW, Judson WE. The use of Rauwolfia serpentina in hypertensive patients. N Engl J Med. 1953 Jan 8;248(2):48-53.
  41. Ryan JJ, Hanes DA, Corroon J, Taylor J, Bradley R. Prospective safety evaluation of a cardiovascular health dietary supplement in adults with prehypertension and stage I hypertension. J Altern Complement Med 2019;25(2):249-56. doi:10.1089/acm.2018.0311. PubMed
  42. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
  43. Schmauss M, Laakmann G, Dieterle D. Effects of alpha 2-receptor blockade in addition to tricyclic antidepressants in therapy-resistant depression. J Clin Psychopharmacol. 1988;8(2):108-11.

See these in context on the Indian Snakeroot monograph →

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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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