Major interaction on record — check this product against your medications before combining. Based on 10 of 12 ingredients. Check your meds →
Dietary supplement

Red Zone Ingredients & Drug Interactions

by Ultimate Nutrition Platinum Series

Red Zone label
See full label image
Other (e.g. Tea Bag) Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 9, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Red Zone 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

Red Zone is a dietary supplement by Ultimate Nutrition Platinum Series with 12 active ingredients. Its ingredients are commonly taken for athletic performance and endurance, high-intensity exercise capacity, reducing muscle fatigue.Based on those ingredients, 1,478 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Asian Ginseng powder, Black Pepper extract, Ginger powder. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Red Zone by Ultimate Nutrition Platinum Series

Ask about any prescription or over-the-counter medication and we check it for interactions with Red Zone by Ultimate Nutrition Platinum Series — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Red Zone by Ultimate Nutrition Platinum Series

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

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 11, 2026

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 0 of its 12 active ingredients.
  • “Fatigue Delay Complex” is a proprietary blend — the label gives one combined amount (1,030 mg) without saying how much of each component you get.
  • “Calorie Burning Complex” is a proprietary blend — the label gives one combined amount (795 mg) without saying how much of each component you get.
  • “Power Enhancing Complex” is a proprietary blend — the label gives one combined amount (500 mg) without saying how much of each component you get.

Red Zone contains 12 ingredients, including several active compounds aimed at athletic performance and energy. Beta-alanine is included for muscle endurance; caffeine anhydrous for mental alertness and physical performance; ginger powder, cayenne pepper, and black pepper extract for their stimulating and circulatory effects; and CoQ-10 (coenzyme Q10) for cellular energy support.

The product also includes kola nut powder, Asian ginseng powder, white willow powder, and red tea extract, along with three proprietary blends labeled Fatigue Delay Complex, Calorie Burning Complex, and Power Enhancing Complex. Inactive ingredients—microcrystalline cellulose, croscarmellose sodium, stearic acid, silica, magnesium stearate, and others—serve as fillers and binders in the tablet coating.

Does it work?

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

Clinical evidence supports at least one of this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: Athletic performance and energy support.
  • We looked for evidence on: Athletic performance, Muscle endurance, Exercise capacity, Physical power.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Beta-alanine is rated "Possibly Effective" for Athletic performance.
  • Also on file: Panax Ginseng is rated "Possibly Ineffective" for Athletic performance.

Beta-alanine is possibly effective for athletic and physical performance. Caffeine is likely effective for mental alertness and athletic performance, and effective for neonatal apnea and postoperative headache.

Ginger is possibly effective for pregnancy-related nausea, period pain (dysmenorrhea), and osteoarthritis, but possibly ineffective for exercise-induced muscle soreness. Cayenne pepper is likely effective for nerve pain after shingles (postherpetic neuralgia) and diabetic nerve pain, and possibly effective for cluster headaches and back pain.

CoQ-10 is likely effective for CoQ-10 deficiency and possibly effective for heart failure, migraines, and diabetic nerve pain. For kola nut powder, Asian ginseng powder, white willow powder, red tea extract, and the proprietary blends, effectiveness data is not on file in our records.

The evidence, ingredient by ingredient Beta-alanine Coenzyme Q10 Ginger Capsicum Cola Nut Panax Ginseng Black Pepper Evodia

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

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

Why this rating?
  • We hold adverse-effect (side-effect) data for 10 of the 10 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 10 of 10.
  • General safety write-ups exist for 10 of 10.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Beta-alanine is generally well tolerated but commonly causes harmless skin tingling (paresthesias), especially on the scalp, starting within 20 minutes and lasting about an hour—less noticeable at lower doses. Avoid during pregnancy and breastfeeding due to insufficient safety data.

Caffeine in moderate amounts is generally tolerated but high doses can cause anxiety, insomnia, restlessness, nausea, tremors, and rarely stroke. Limit intake during pregnancy and talk with your doctor about safe amounts; small amounts pass into breast milk and moderate intake is usually acceptable.

Ginger is generally well tolerated at typical amounts; at higher doses (above 5 grams daily) it can cause stomach discomfort, heartburn, and diarrhea. It is likely safe in pregnancy and breastfeeding.

Cayenne pepper is generally safe as food but concentrated supplements are not well studied; it commonly causes burning and digestive upset. Food amounts are likely fine in pregnancy and breastfeeding; avoid concentrated supplements without medical approval.

CoQ-10 is generally well tolerated with minimal side effects; gastrointestinal upset (nausea, diarrhea) occurs in less than 1% of users. Avoid during pregnancy unless your doctor advises; safety while breastfeeding is not well studied.

Black pepper extract is generally safe in food amounts; concentrated supplements should be used cautiously. Evodia extract has limited human safety data and should be used carefully under professional guidance; avoid during pregnancy and breastfeeding.

Side effects, ingredient by ingredient Beta-alanine Coenzyme Q10 Ginger Capsicum Cola Nut Panax Ginseng Black Pepper Evodia

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

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

Why this rating?
  • 9 of the 10 matched ingredients can interact with medications — Grape, Black Pepper, Cola Nut, Coenzyme Q10, Capsicum, 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.
  • For scale: 1,479 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking Red Zone, double-check with your pharmacist or doctor if you take: ephedrine or any stimulant (Major risk); blood thinners or antiplatelet drugs like warfarin, clopidogrel, or aspirin (Moderate); diabetes medications (Moderate); heart or blood pressure drugs including beta-blockers like propranolol, nifedipine, or losartan (Moderate); seizure medications like phenytoin, carbamazepine, or phenobarbital (Moderate); antipsychotics like clozapine (Moderate); theophylline or other asthma/breathing medications (Moderate); quinolone antibiotics, rifampin, or nevirapine (Moderate); barbiturates or pentobarbital (Moderate); the acid reflux medication cimetidine (Moderate); dipyridamole for cardiac stress testing (Moderate); cyclosporine for transplant rejection (Moderate); or QT-prolonging heart rhythm medications (Moderate). No interactions are documented in our data for beta-alanine.

Check your own medication Run your meds through the checker above

The bottom line

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

Red Zone is designed for people looking to boost athletic performance and energy through caffeine, beta-alanine, and herbal extracts. However, if you take any prescription medications—particularly blood thinners, diabetes drugs, heart medications, seizure medications, or antipsychotics—you need to check your exact drugs against the medication interactions listed below before starting.

Talk with your pharmacist or doctor first, especially if you're pregnant, breastfeeding, or have high blood pressure or heart conditions.

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

Assessment coverage: 10 of 12 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Dec 23, 2011.

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 Red Zone, straight from the product label.

Brand Ultimate Nutrition Platinum Series
Barcode (UPC) 099071005618
Net contents 120 Caplet(s)
Market status Off market
Date entered into DSLD Dec 23, 2011
DSLD ID 4024
Product type Other Combinations
Supplement form Other (e.g. Tea Bag)
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Red Zone by Ultimate Nutrition Platinum Series, 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:
3 Caplet(s)
Maximum serving Sizes:
3 Caplet(s)
Servings per container
40
UPC/BARCODE
099071005618
IngredientAmount% DV
Beta-Alanine0 NP--
Caffeine Anhydrous0 NP--
Ginger powder0 NP--
Cayenne Pepper0 NP--
Kola Nut powder0 NP--
Asian Ginseng powder0 NP--
White Willow powder0 NP--
Black Pepper extract0 NP--
Evodia extract0 NP--
Fatigue Delay Complex1030 mg--
CO Q-100 NP--
Calorie Burning Complex795 mg--
Red Tea extract0 NP--
Power Enhancing Complex500 mg--
PowerGrape0 NP--

Other ingredients: Microcrystalline Cellulose, Croscarmellose Sodium, Stearic Acid, Silica, Magnesium Stearate, Hydroxy Propyl Methyl Cellulose, Triacetin, FD&C Red #40, Talc, Carnauba Wax, Povidone

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 Statement of Identity

Multi-ingredient Supplement

Suggested/Recommended/Usage/Directions

Directions: As a dietary supplement, take 3 caplets with 8 oz. water twice daily, once in the morning and again mid-afternoon. On training days, take one serving 30 minutes before your workout. Do not exceed 6 caplets per day. Do not take within 6 hours of sleep.

Precautions

• Keep out of reach of children

• Tamper Resistant: Do not use if seal under cap is broken or missing

Warning: Too much caffeine may cause nervousness, irritability, sleeplessness and occasionally, rapid heartbeat. Not recommended for use by children under 18 years of age.

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.

Storage

• Store in a cool dry place

Formula

Contains tree nut (kola)

Red Zone contains 100mg of caffeine per serving.

Get into your body’s red zone, with Ultimate Nutrition Red Zone(TM). This revolutionary hardcore fat burner not only boosts calorie burn, but also extends your workouts and increases your power. Blow through the weights and cardiovascular activity with a 21.1% increase in power delivered through the powerenhancing blend of PowerGrape(R) and caffeine. The fatigue-delaying complex combines the precise blend of COQ-10 and beta alanine that have been clinically studied to extend workouts. Work out harder, longer and burn fat faster with Ultimate Nutrition Red Zone(tm).

General Statements

21.1% Increase in Power*†

Burn Fat Faster*

Daily Pre During Post Night

Delay Exhaustion*

POWER INCREASE 10% 20% RedZone Placebo

Brand IP Statement(s)

† In a placebo controlled, double-blind, crossover, randomized clinically trial of 20 sportsmen, there was a significant increase of 21.1% in performance power by those who took the clinically research amount of PowerGrape(R) that is found in Red Zone(TM).

PowerGrape(R) is a trademark of Naturex Inc.

with powergrape(R)

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

See for yourself

Red Zone by Ultimate Nutrition Platinum Series label

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

Red Zone 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 Red Zone by Ultimate Nutrition Platinum Series

These are the 12 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Caplet(s) Dosage formOther (e.g. Tea Bag) Servings per container40 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.

Fatigue Delay Complex

1030 mg per serving

Calorie Burning Complex

795 mg per serving

Power Enhancing Complex

500 mg per serving

Other (inactive) ingredients: Microcrystalline Cellulose, Croscarmellose Sodium, Stearic Acid, Silica, Magnesium Stearate, Hydroxy Propyl Methyl Cellulose, Triacetin, FD&C Red #40, Talc, Carnauba Wax, Povidone. These complete the product’s ingredient list but are not active constituents.

Interaction report

Red Zone by Ultimate Nutrition Platinum Series Drug Interactions

Want to check YOUR meds against Red Zone?

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
1,478Drugs
8 Major 1,377 Moderate 93 Minor

Ingredients driving the most interactions

Asian Ginseng powder 1,130
Black Pepper extract 1,019
Ginger powder 1,007
Evodia extract 950
PowerGrape 910

Individual Drug Interactions

The ingredients in Red Zone interact with 1,478 drugs. Click any drug to see the details.

9 of the 12 ingredients in Red Zone interact with drugs. Each result below shows which ingredient is responsible. Asian Ginseng powder Black Pepper extract Ginger powder Evodia extract PowerGrape Kola Nut powder Caffeine Anhydrous Cayenne Pepper CO Q-10

Each ingredient & the kinds of drugs it affects

For each ingredient in Red Zone 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.

Asian Ginseng powder20 drug types · 1,130 drugs

Anticoagulant/Antiplatelet Drugs

Although Panax ginseng has shown antiplatelet effects in the laboratory, it is unlikely to increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that ginsenoside constituents in Panax ginseng might decrease platelet aggregation. However, research in humans suggests that ginseng does not affect platelet aggregation. Animal research indicates low oral bioavailability of Rb1 and rapid elimination of Rg1, which might explain the discrepancy between in vitro and human research. Until more is known, use with caution in patients concurrently taking anticoagulant or antiplatelet drugs.

Likelihood Unlikely Evidence B
Antidiabetes Drugs

Theoretically, taking Panax ginseng with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research suggests that Panax ginseng might decrease blood glucose levels. Monitor blood glucose levels closely.

Likelihood Probable Evidence B
Caffeine

Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects. Theoretically, caffeine might have an additive effect on the stimulant effects of Panax ginseng.

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

Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.
There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6%. In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount. However, contradictory research suggests Panax ginseng might not inhibit CYP2D6. Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.
Panax ginseng may affect the clearance of drugs metabolized by CYP3A4. One such drug is imatinib. Inhibition of CYP3A4 was believed to be responsible for a case of imatinib-induced hepatotoxicity. In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4. Clinical research shows that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng. Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.

Likelihood Possible Evidence B
Estrogens

Theoretically, concomitant use of large amounts of Panax ginseng might interfere with hormone replacement therapy.
Laboratory research and some case reports suggest that Panax ginseng can have estrogenic effects due to competition for estrogen receptors. The estrogenic activity is attributed to the ginsenoside constituents of Panax ginseng.

Likelihood Possible Evidence D
Furosemide (Lasix)

Theoretically, Panax ginseng might reduce the effects of furosemide.
There is some concern that Panax ginseng might contribute to furosemide resistance. There is one case of resistance to furosemide diuresis in a patient taking a germanium-containing ginseng product.

Likelihood Possible Evidence D
Imatinib (Gleevec)

Theoretically, Panax ginseng might increase the effects and adverse effects of imatinib.
A case of imatinib-induced hepatotoxicity has been reported for a 26-year-old male with chronic myelogenous leukemia stabilized on imatinib for 7 years. The patient took imatinib 400 mg along with a Panax ginseng-containing energy drink daily for 3 months. Since imatinib-associated hepatotoxicity typically occurs within 2 years of initiating therapy, it is believed that Panax ginseng affected imatinib toxicity though inhibition of cytochrome P450 3A4. CYP3A4 is the primary enzyme involved in imatinib metabolism.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, Panax ginseng use might interfere with immunosuppressive therapy.
Panax ginseng might have immune system stimulating properties.

Likelihood Possible Evidence B
Insulin

Theoretically, taking Panax ginseng with insulin might increase the risk of hypoglycemia.
Clinical research suggests that Panax ginseng might decrease blood glucose levels. Insulin dose adjustments might be necessary in patients taking Panax ginseng; use with caution.

Likelihood Probable Evidence B
Midazolam (Versed)

Theoretically, Panax ginseng may increase the clearance of midazolam.
Midazolam is metabolized by cytochrome P450 3A4 (CYP3A4). Clinical research suggests that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng.

Likelihood Probable Evidence B
Monoamine Oxidase Inhibitors (Maois)

Theoretically, Panax ginseng can interfere with MAOI therapy.
Concomitant use of Panax ginseng with phenelzine (Nardil) is associated with insomnia, headache, tremors, and hypomania.

Likelihood Probable Evidence D
Nifedipine (Procardia)

Theoretically, taking Panax ginseng with nifedipine might increase serum levels of nifedipine and the risk of hypotension.
Preliminary clinical research shows that concomitant use can increase serum levels of nifedipine in healthy volunteers. This might cause the blood pressure lowering effects of nifedipine to be increased when taken concomitantly with Panax ginseng.

Likelihood Possible Evidence B
Qt Interval-Prolonging Drugs

Theoretically, Panax ginseng has an additive effect with drugs that prolong the QT interval and potentially increase the risk of ventricular arrhythmias. However, research is conflicting.
Clinical research shows that short-term use of Panax ginseng can increase the QT interval. However, no changes in QT interval have been identified with prolonged use.

Likelihood Possible Evidence B
Raltegravir (Isentress)

Theoretically, taking Panax ginseng with raltegravir might increase the risk of liver toxicity.
A case report suggests that concomitant use of Panax ginseng with raltegravir can increase serum levels of raltegravir, resulting in elevated liver enzymes levels.

Likelihood Possible Evidence D
Selegiline (Eldepryl)

Theoretically, Panax ginseng might increase or decrease levels of selegiline, possibly altering the effects and side effects of selegiline.
Animal research shows that taking selegiline with a low dose of Panax ginseng extract (1 gram/kg) reduces selegiline bioavailability, while taking a high dose of Panax ginseng extract (3 grams/kg) increases selegiline bioavailability. More research is needed to confirm these effects.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Panax ginseng might affect the clearance of warfarin. However, this interaction appears to be unlikely.
There has been a single case report of decreased effectiveness of warfarin in a patient who also took Panax ginseng. However, it is questionable whether Panax ginseng was the cause of this decrease in warfarin effectiveness. Some research in humans and animals suggests that Panax ginseng does not affect the pharmacokinetics of warfarin. However, other research in humans suggests that Panax ginseng might modestly increase the clearance of the S-warfarin isomer. More evidence is needed to determine whether Panax ginseng causes a significant interaction with warfarin.

Likelihood Unlikely Evidence B
Fexofenadine (Allegra)

Theoretically, Panax ginseng might decrease blood levels of oral or intravenous fexofenadine.
Animal research suggests that taking Panax ginseng in combination with oral or intravenous fexofenadine may reduce the bioavailability of fexofenadine. Some scientists have attributed this effect to the ability of Panax ginseng to increase the expression of P-glycoprotein.

Likelihood Possible Evidence D
Lopinavir/Ritonavir (Kaletra)

Although Panax ginseng has demonstrated variable effects on cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir, Panax ginseng is unlikely to alter levels of lopinavir/ritonavir.
Lopinavir is metabolized by CYP3A4 and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Panax ginseng has shown variable effects on CYP3A4 activity in humans. However, taking Panax ginseng (Vitamer Laboratories) 500 mg twice daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in 12 healthy volunteers.

Likelihood Unlikely Evidence B
Asian Ginseng powder full monograph & interactions

Black Pepper extract17 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 extract full monograph & interactions

Ginger powder14 drug types · 1,007 drugs

Anticoagulant/Antiplatelet Drugs

Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation. However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials. Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels.

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

Ginger might increase or decrease the levels of CYP3A4 substrates.
In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity. Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Losartan (Cozaar)

Theoretically, ginger might increase levels of losartan and the risk of hypotension.
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan. It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

Likelihood Possible Evidence D
Nifedipine (Procardia)

Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.

Likelihood Possible Evidence D
Phenprocoumon (Marcoumar, Others)

Ginger might increase the risk of bleeding with phenprocoumon.
Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Ginger might increase the risk of bleeding with warfarin.
Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation. In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin. In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen. A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months. However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. Until more is known, monitor INRs closely in patients taking large amounts of ginger.

Likelihood Possible Evidence B
Calcium Channel Blockers

Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects. Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone.

Likelihood Unlikely Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time.

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

Theoretically, ginger might increase the levels of CYP1A2 substrates.
In vitro research shows that ginger inhibits CYP1A2 activity. However, this interaction has not been reported in humans.

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

Theoretically, ginger might increase the levels of CYP2B6 substrates.
In vitro research shows that ginger inhibits CYP2B6 activity. However, this interaction has not been reported in humans.

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

Theoretically, ginger might increase the levels of CYP2C9 substrates.
In vitro research shows that ginger inhibits CYP2C9 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Metronidazole (Flagyl)

Theoretically, ginger might increase levels of metronidazole.
In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced.

Likelihood Possible Evidence D
Ginger powder full monograph & interactions

Evodia extract11 drug types · 950 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, taking evodia with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.
In vitro and animal studies show that rutaecarpine, a constituent of evodia, inhibits platelet aggregation.

Likelihood Possible Evidence D
Caffeine

Theoretically, evodia might decrease the levels and clinical effects of caffeine.
In animal models, evodia extract decreases caffeine levels by up to 71%. Evodia extract induces hepatic cytochrome P450 1A2 (CYP1A2) enzyme, of which caffeine is a substrate.

Likelihood Probable Evidence D
Chlorzoxazone (Parafon Forte, Paraflex)

Theoretically, evodia might decrease the levels and clinical effects of chlorzoxazone.
Animal research shows that administration of rutaecarpine, a constituent of evodia, with chlorzoxazone reduces the area under the curve (AUC) of chlorzoxazone by 84% and increases its clearance by 646%. This interaction is likely due to induction of cytochrome P450 2E1 (CYP2E1) by rutaecarpine .

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

Theoretically, drugs that inhibit CYP1A2 might increase the levels and clinical effects of evodia.
The evodia constituent rutaecarpine is metabolized by CYP1A2.

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

Evodia might reduce the levels and clinical effects of CYP1A2 substrates through induction of CYP1A2.
Evodia extract and the evodia constituent rutaecarpine induce hepatic CYP1A2 enzyme activity. Evodia decreases levels of theophylline and caffeine, CYP1A2 substrates, by about 70% in animal models.

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

Theoretically, evodia might reduce the levels and clinical effects of CYP2E1 substrates through induction of CYP2E1.
Animal research suggests that rutaecarpine, a constituent of evodia, induces CYP2E1 activity. In rats, rutaecarpine increases markers of CYP2E1 activity, and administration of rutaecarpine with chlorzoxazone, a known CYP2E1 substrate, reduces the area under the curve (AUC) of chlorzoxazone by 84% and increases its clearance by 646%.

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

Theoretically, taking CYP3A4 inducers might decrease the levels and clinical effects of evodia.
Animal research shows that concomitant administration of dexamethasone, a known CYP3A4 inducer, with the alkaloid constituents of evodia significantly reduces the area under the curve (AUC), maximum concentration (Cmax), and half-life of these constituents.

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

Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of evodia.
Animal research shows that concomitant administration of ketoconazole, a known CYP3A4 inhibitor, with the alkaloid constituents of evodia significantly increases the area under the curve (AUC), maximum concentration (Cmax), and half-life of these constituents.

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

Theoretically, evodia might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that evodia extract inhibits hepatic CYP3A4. This effect has not been reported in humans.

Likelihood Possible Evidence D
Qt Interval-Prolonging Drugs

Theoretically, evodia might have an additive effect with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.
Evodia has demonstrated dose-dependent activity as a proarrhythmic agent in animal and in vitro studies. Evodia infusion in animals extends the action duration potential and induces prolongation of the QT interval and Torsade de pointes.

Likelihood Possible Evidence D
Theophylline

Theoretically, evodia might decrease the levels and clinical effects of theophylline.
The evodia constituent rutaecarpine decreases theophylline levels and half-life by about 70% in animal models. This constituent appears to induce hepatic cytochrome P450 1A2 (CYP1A2) enzyme activity, of which theophylline is a substrate. Rutaecarpine is the primary active constituent of evodia; however, it is not known if the whole crude extract of evodia also causes this interaction.

Likelihood Probable Evidence D
Evodia extract full monograph & interactions

PowerGrape9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

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

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

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

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

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

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

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

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

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

Likelihood Possible Evidence D
Midazolam (Versed)

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

Likelihood Possible Evidence D
Phenacetin

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

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

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

Likelihood Unlikely Evidence D
PowerGrape full monograph & interactions

Kola Nut powder41 drug types · 655 drugs

Adenosine (Adenocard)

Theoretically, cola nut might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Cola nut 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 (including cola nut) 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
Alcohol (Ethanol)

Theoretically, alcohol might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, cola nut may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Cola nut contains caffeine. Caffeine is reported to have antiplatelet activity. This interaction has not been reported in humans.

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

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

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

Theoretically, cola nut might reduce the effects of carbamazepine and increase the risk for convulsions.
Cola nut 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
Clozapine (Clozaril)

Theoretically, cola nut might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Cola nut 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 more sensitive to the interaction between clozapine and caffeine.

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

Theoretically, CYP1A2 inhibitors might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. Caffeine is metabolized by CYP1A2,.

Likelihood Possible Evidence D
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

Theoretically, disulfiram might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance.

Likelihood Probable Evidence D
Diuretic Drugs

Theoretically, using cola nut with diuretic drugs might increase the risk of hypokalemia.
Cola nut contains caffeine. In excessive amounts, caffeine can reduce potassium levels due to stimulation of the sodium-potassium pump. Certain diuretics can also lower potassium levels.

Likelihood Possible Evidence D
Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Cola nut 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 the caffeine in cola nut.
Cola nut contains caffeine. Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, cola nut might reduce the effects of ethosuximide and increase the risk for convulsions.
Cola nut 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, cola nut might reduce the effects of felbamate and increase the risk for convulsions.
Cola nut 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
Flutamide (Eulexin)

Theoretically, cola nut might increase the levels and adverse effects of flutamide.
Cola nut contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. This effect has not been reported in humans.

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

Theoretically, fluvoxamine might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. Fluvoxamine reduces caffeine metabolism.

Likelihood Probable Evidence D
Lithium

Theoretically, abrupt cola nut withdrawal might increase the levels and adverse effects of lithium.
Cola nut contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Probable Evidence D
Pentobarbital (Nembutal)

Theoretically, cola nut might decrease the effects of pentobarbital.
Cola nut contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

Theoretically, cola nut might reduce the effects of phenobarbital and increase the risk for convulsions.
Cola nut contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Phenylpropanolamine

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of the caffeine in cola nut.
Cola nut 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, cola nut might reduce the effects of phenytoin and increase the risk for convulsions.
Cola nut 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
Pioglitazone (Actos)

Theoretically, cola nut might increase the levels and clinical effects of pioglitazone.
Cola nut 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 the caffeine in cola nut.
Cola nut contains caffeine. Quinolones (also called fluoroquinolones) can decrease caffeine clearance by inhibiting cytochrome P450 1A2 (CYP1A2).

Likelihood Probable Evidence B
Kola Nut powder full monograph & all 41 interactions

Caffeine Anhydrous41 drug types · 655 drugs

Ephedrine

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

Likelihood Probable Evidence D
Adenosine (Adenocard)

Theoretically, caffeine might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Some evidence shows that caffeine is a competitive inhibitor of adenosine and can reduce the vasodilatory effects of adenosine in humans. However, other research shows that caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Caffeine is reported to have antiplatelet activity. Theoretically, it might increase the risk of bleeding when used concomitantly with these agents; however, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

Theoretically, large amounts of caffeine might increase the cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

Theoretically, caffeine might reduce the effects of carbamazepine and increase the risk for convulsions.
Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when 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
Cimetidine (Tagamet)

Theoretically, cimetidine might increase the levels and adverse effects of caffeine.
Cimetidine decreases the rate of caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Caffeine might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Caffeine might increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg per day inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Although researchers speculate that caffeine might inhibit CYP1A2, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine. In one case report, severe, life-threatening clozapine toxicity and multiorgan system failure occurred in a patient with schizophrenia stabilized on clozapine who consumed caffeine 600 mg daily.

Likelihood Possible Evidence B
Dipyridamole (Persantine)

Theoretically, caffeine might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Caffeine inhibits 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 use might increase the levels and adverse effects of caffeine.
Disulfiram decreases the rate of caffeine clearance.

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, using caffeine with diuretic drugs might increase the risk of hypokalemia.
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.
Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.
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, caffeine might reduce the effects of felbamate and increase the risk for convulsions.
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
Flutamide (Eulexin)

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

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

Abrupt caffeine withdrawal might increase the levels and adverse effects of lithium.
Caffeine has diuretic activity. When abruptly discontinued, caffeine may alter the clearance of lithium. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal and 6 case reports of elevated serum lithium levels after reducing or eliminating caffeine intake. In one case, a male with schizoaffective disorder stabilized on lithium had an elevated lithium level after reducing his caffeine intake by 87%. At a later date, he increased his caffeine intake by 6-fold, resulting in a subtherapeutic lithium level and a recurrence of psychiatric symptoms.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
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.
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, caffeine might decrease the effects of pentobarbital.
Caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

Theoretically, caffeine might reduce the effects of phenobarbital and increase the risk for convulsions.
Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. However, 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.
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, caffeine might reduce the effects of phenytoin and increase the risk for convulsions.
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
Pioglitazone (Actos)

Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
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.
Quinolones (also called fluoroquinolones) can decrease caffeine clearance by inhibiting cytochrome P450 1A2 (CYP1A2) enzyme.

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Caffeine Anhydrous full monograph & all 41 interactions

Cayenne Pepper6 drug types · 239 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, capsicum may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro research shows that capsicum might increase the effects of antiplatelet drugs. Also, population research shows that capsicum is associated with an increased risk of self-reported bleeding in patients taking warfarin. However, clinical research shows that taking a single dose of capsaicin (Asian Herbex Ltd.), the active ingredient in capsicum, 400-800 mcg orally in combination with aspirin 500 mg does not decrease platelet aggregation when compared with taking aspirin 500 mg alone. Also, there was no notable effect on measures of platelet aggregation with capsaicin. It is unclear whether capsaicin must be used in more than a single dose to affect platelet aggregation.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking capsicum with antidiabetes drugs might increase the risk of hypoglycemia.
Preliminary clinical research shows that consuming capsicum 5 grams along with a glucose drink attenuates the rise in plasma glucose after 30 minutes by 21%, decreases the 2-hour postprandial area under the curve of plasma glucose by 11%, and increases the 2-hour postprandial area under the curve of plasma insulin by 58% in healthy individuals when compared with placebo. Other clinical research shows that taking capsicum 5 mg daily for 28 days significantly reduces postprandial blood glucose and insulin levels, but not fasting blood glucose and insulin levels, in patients with gestational diabetes.

Likelihood Possible Evidence B
Aspirin

Theoretically, taking capsicum with aspirin might reduce the bioavailability of aspirin.
Animal research shows that acute or chronic intake of capsicum pepper reduces oral aspirin bioavailability. This has not been shown in humans.

Likelihood Possible Evidence D
Theophylline

Theoretically, taking capsicum with theophylline might increase the levels and adverse effects of theophylline.
In animal research, oral administration of capsicum reduced excretion of theophylline. However, capsicum does not seem to affect the pharmacokinetics of theophylline when administered intravenously.

Likelihood Possible Evidence D
Ace Inhibitors (Aceis)

Theoretically, using topical capsaicin may increase the risk of ACE inhibitor-induced cough.
There is one case report of a topically applied capsaicin cream contributing to the cough reflex in a patient using an ACEI. However, it is unclear if this interaction is clinically significant.

Likelihood Unlikely Evidence D
Ciprofloxacin (Cipro)

Theoretically, taking capsicum with ciprofloxacin might increase levels and adverse effects of ciprofloxacin.
Animal research shows that concomitant use of capsaicin, the active constituent of capsicum, and ciprofloxacin increases the bioavailability of ciprofloxacin by up to 70%.

Likelihood Possible Evidence D
Cayenne Pepper full monograph & interactions

CO Q-103 drug types · 198 drugs

Alkylating Agents

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

Likelihood Possible Evidence D
Warfarin (Coumadin)

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

Likelihood Possible Evidence D
Antihypertensive Drugs

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

Likelihood Possible Evidence B
CO Q-10 full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Red Zone, from the product label.

Ultimate Nutrition Platinum Series

See all Ultimate Nutrition Platinum Series products
Name
Ultimate Nutrition Inc.
Street Address
P.O. Box 643
City
Farmington
State
CT
ZipCode
06034
Pharmacist Counseling Corner

Red Zone by Ultimate Nutrition Platinum Series: Common Questions

Does Red Zone by Ultimate Nutrition Platinum Series interact with any medications?
Yes. Based on its ingredients, Red Zone has a known interaction with 1,478 medications, including 8 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Red Zone contains 12 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.
Does Red Zone really improve athletic performance?
Beta-alanine and caffeine in Red Zone are both rated possibly or likely effective for athletic performance in our data. However, individual results vary, and effects depend on your training, diet, and how your body responds to these ingredients.
What's that tingling feeling I might get from this product?
That's the beta-alanine causing harmless skin tingling (paresthesias), usually starting on the scalp within 20 minutes and lasting about an hour. It's more noticeable at higher doses and tends to fade as your body adjusts. It's not dangerous.
Is it safe to take Red Zone if I'm pregnant?
Beta-alanine and evodia extract should be avoided during pregnancy due to insufficient safety data. Caffeine should be limited—talk with your doctor about what dose is safe for you. Ginger, cayenne, and grape extract are likely safe at food amounts in pregnancy, but concentrated supplements are less certain. Check with your doctor or pharmacist before starting.
Can I take Red Zone while breastfeeding?
Beta-alanine and evodia extract should be avoided while breastfeeding. Caffeine passes into breast milk in small amounts; moderate intake is usually acceptable but talk with your doctor. Ginger and cayenne are likely safe at food amounts. CoQ-10 and black pepper safety while breastfeeding haven't been well studied—ask your pharmacist for personalized advice.
What are the most common side effects?
Beta-alanine causes skin tingling in most users. Caffeine commonly causes anxiety, jitteriness, insomnia, and restlessness. Ginger and cayenne can cause stomach discomfort, heartburn, and diarrhea, especially at higher doses. These are generally mild, but if they're bothersome, talk with your pharmacist about adjusting your dose or timing.
Why do I need to check my medications before taking this?
Red Zone contains caffeine, ginger, cayenne, black pepper, evodia, CoQ-10, and grape extract—all of which interact with common prescription drugs. These interactions can make your medications less effective or increase their side effects. Your pharmacist can check your exact medications against this product to make sure it's safe for you.

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

Not sure if Red Zone is safe with your meds?

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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.

Red Zone label
Go deeper

The Full Monographs Behind Red Zone’s Ingredients

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

Herb & supplement monograph

Beta-alanine

Beta-alanine is an amino acid taken mostly by athletes to raise muscle carnosine, which may help buffer acid and reduce fatigue during short, high-intensity exercise. The evidence is moderat...

Read the full Beta-alanine monograph → Herb & supplement monograph

Coenzyme Q10

Interacts with 198 drugs

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

Read the full Coenzyme Q10 monograph → Herb & supplement monograph

Ginger

Interacts with 1,007 drugs

Ginger is a widely used culinary spice with a long history in traditional medicine, and it has the strongest evidence for helping with nausea and vomiting, including from motion sickness, pr...

Read the full Ginger monograph → Herb & supplement monograph

Capsicum

Interacts with 239 drugs

Capsicum (chili pepper) contains capsaicin, which is best known and best studied as a topical treatment for certain types of pain. Topical capsaicin products are supported by reasonable evid...

Read the full Capsicum monograph → Herb & supplement monograph

Cola Nut

Interacts with 655 drugs

Cola nut is a caffeine-containing seed from West Africa used mainly as a natural stimulant for energy and alertness. Most of its effects come from caffeine, and strong human evidence for spe...

Read the full Cola Nut monograph → Herb & supplement monograph

Panax Ginseng

Interacts with 1,130 drugs

Panax ginseng is a popular traditional herb used to boost energy, ease stress, and support overall wellness, though scientific evidence is mixed and mostly preliminary. It is generally well...

Read the full Panax Ginseng 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

Evodia

Interacts with 950 drugs

Evodia is a fruit used in traditional Chinese medicine, most often for digestive complaints, headaches, and menstrual pain. Human evidence for these uses is very limited, and it is mostly st...

Read the full Evodia monograph → Herb & supplement monograph

Caffeine

Interacts with 655 drugs

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too muc...

Read the full Caffeine monograph → Herb & supplement monograph

Grape

Interacts with 910 drugs

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

Read the full Grape monograph →
Sources

Sources & How We Checked

Red Zone'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 741 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.

Beta-alanine 13 references
  1. Harris RC, Tallon MJ, Dunnett M, et al. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids 2006;30:279-89.
  2. Hill CA, Harris RC, Kim HJ, et al. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids 2007;32:225-33.
  3. Bellinger PM, Minahan CL. The effect of ß-alanine supplementation on cycling time trials of different length. Eur J Sport Sci 2016;16(7):829-36.
  4. Chung W, Shaw G, Anderson ME, et al. Effect of 10 week beta-alanine supplementation on competition and training performance in elite swimmers. Nutrients 2012;4(10):1441-53. PubMed
  5. Glenn JM, Gray M, Stewart R, et al. Incremental effects of 28 days of beta-alanine supplementation on high-intensity cycling performance and blood lactate in masters female cyclists. Amino Acids 2015;47(12):2593-600. PubMed
  6. Gross M, Bieri K, Hoppeler H, Norman B, Vogt M. Beta-alanine supplementation improves jumping power and affects severe-intensity performance in professional alpine skiers. Int J Sport Nutr Exerc Metab 2014;24(6):665-73. PubMed
  7. Howe ST, Bellinger PM, Driller MW, Shing CM, Fell JW. The effect of beta-alanine supplementation on isokinetic force and cycling performance in highly trained cyclists. Int J Sport Nutr Exerc Metab 2013;23(6):562-70. PubMed
  8. Sweeney KM, Wright GA, Glenn Brice A, Doberstein ST. The effect of beta-alanine supplementation on power performance during repeated sprint activity. J Strength Cond Res 2010;24(1):79-87.
  9. Décombaz J, Beaumont M, Vuichoud J, Bouisset F, Stellingwerff T. Effect of slow-release ß-alanine tablets on absorption kinetics and paresthesia. Amino Acids 2012;43(1):67-76. Erratum in: Amino Acids 2013;45(4):1015.
  10. Stellingwerff T, Anwander H, Egger A, et al. Effect of two ß-alanine dosing protocols on muscle carnosine synthesis and washout. Amino Acids 2012;42(6):2461-72. PubMed
  11. da Silva RP, de Oliveira LF, Saunders B, et al. Effects of ß-alanine and sodium bicarbonate supplementation on the estimated energy system contribution during high-intensity intermittent exercise. Amino Acids. 2019;51(1):83-96. PubMed
  12. Varanoske AN, Hoffman JR, Church DD, et al. Comparison of sustained-release and rapid-release ß-alanine formulations on changes in skeletal muscle carnosine and histidine content and isometric performance following a muscle-damaging protocol. Amino Acids. PubMed
  13. Perim P, Gobbi N, Duarte B, et al. Beta-alanine did not improve high-intensity performance throughout simulated road cycling. Eur J Sport Sci 2021. PubMed

See these in context on the Beta-alanine monograph →

Caffeine 236 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  8. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  9. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  10. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  11. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  12. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  13. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  14. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  15. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed
  16. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  17. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. PubMed
  18. Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. PubMed
  19. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  20. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  21. 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
  22. Tobias JD. Caffeine in the treatment of apnea associated with respiratory syncytial virus infection in neonates and infants. South Med J 2000;93:297-304. DOI
  23. 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
  24. 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
  25. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  26. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  27. 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
  28. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  29. 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
  30. 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
  31. Avisar R, Avisar E, Weinberger D. Effect of coffee consumption on intraocular pressure. Ann Pharmacother 2002;36:992-5.. PubMed
  32. 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
  33. 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
  34. 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
  35. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  36. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  37. Dreher HM. The effect of caffeine reduction on sleep quality and well-being in persons with HIV. J Psychosom Res 2003;54:191-8.. PubMed
  38. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  39. Schechter MD, Timmons GD. Objectively measured hyperactivity--II. Caffeine and amphetamine effects. J Clin Pharmacol 1985;25:276-80.. PubMed
  40. 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
  41. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  42. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  43. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  44. 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
  45. 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
  46. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  47. 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
  48. 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
  49. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  50. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  51. 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
  52. 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.
  53. 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
  54. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  55. 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
  56. 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
  57. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  58. 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
  59. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  60. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  61. 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
  62. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  63. 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.
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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
  69. 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.
  70. 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
  71. 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
  72. 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.
  73. 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
  74. Balogh, A., Klinger, G., Henschel, L., Borner, A., Vollanth, R., and Kuhnz, W. Influence of ethinylestradiol-containing combination oral contraceptives with gestodene or levonorgestrel on caffeine elimination. Eur.J.Clin.Pharmacol. 1995;48(2):161-166. PubMed
  75. 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.
  76. 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
  77. 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
  78. 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.
  79. 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
  80. Bailey, D. N., Weibert, R. T., Naylor, A. J., and Shaw, R. F. A study of salicylate and caffeine excretion in the breast milk of two nursing mothers. J.Anal.Toxicol. 1982;6(2):64-68. PubMed
  81. Griffiths, R. R. and Chausmer, A. L. Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Nihon Shinkei Seishin Yakurigaku Zasshi 2000;20(
  82. Karacan, I., Thornby, J. I., Anch, M., Booth, G. H., Williams, R. L., and Salis, P. J. Dose-related sleep disturbances induced by coffee and caffeine. Clin Pharmacol Ther 1976;20(6):682-689. PubMed
  83. Quirce, G. S., Freire, P., Fernandez, R. M., Davila, I., and Losada, E. Urticaria from caffeine. J.Allergy Clin Immunol. 1991;88(4):680-681. PubMed
  84. Hughes, J. R., Higgins, S. T., Bickel, W. K., Hunt, W. K., Fenwick, J. W., Gulliver, S. B., and Mireault, G. C. Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Arch.Gen.Psychiatry 1991;48(7):611-617. PubMed
  85. Adams, B. A. and Brubaker, R. F. Caffeine has no clinically significant effect on aqueous humor flow in the normal human eye. Ophthalmology 1990;97(8):1030-1031. PubMed
  86. Davis, R. H. Does caffeine ingestion affect intraocular pressure?. Ophthalmology 1989;96(11):1680-1681. PubMed
  87. Higginbotham, E. J., Kilimanjaro, H. A., Wilensky, J. T., Batenhorst, R. L., and Hermann, D. The effect of caffeine on intraocular pressure in glaucoma patients. Ophthalmology 1989;96(5):624-626.
  88. Wrenn, K. D. and Oschner, I. Rhabdomyolysis induced by a caffeine overdose. Ann.Emerg.Med. 1989;18(1):94-97. PubMed
  89. Pola, J., Subiza, J., Armentia, A., Zapata, C., Hinojosa, M., Losada, E., and Valdivieso, R. Urticaria caused by caffeine. Ann.Allergy 1988;60(3):207-208.
  90. Lane, J. D. and Williams, R. B., Jr. Cardiovascular effects of caffeine and stress in regular coffee drinkers. Psychophysiology 1987;24(2):157-164. PubMed
  91. Shirlow, M. J. and Mathers, C. D. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. Int.J.Epidemiol. 1985;14(2):239-248. PubMed
  92. Stillner, V., Popkin, M. K., and Pierce, C. M. Caffeine-induced delirium during prolonged competitive stress. Am.J.Psychiatry 1978;135(7):855-856. PubMed
  93. Levy, M. and Zylber-Katz, E. Caffeine metabolism and coffee-attributed sleep disturbances. Clin Pharmacol Ther 1983;33(6):770-775. PubMed
  94. Brown, S. L., Salive, M. E., Pahor, M., Foley, D. J., Corti, M. C., Langlois, J. A., Wallace, R. B., and Harris, T. B. Occult caffeine as a source of sleep problems in an older population. J.Am.Geriatr.Soc. 1995;43(8):860-864. PubMed
  95. Sung, B. H., Whitsett, T. L., Lovallo, W. R., al'Absi, M., Pincomb, G. A., and Wilson, M. F. Prolonged increase in blood pressure by a single oral dose of caffeine in mildly hypertensive men. Am.J Hypertens. 1994;7(8):755-758. PubMed
  96. Caballero, T., Garcia-Ara, C., Pascual, C., Diaz-Pena, J. M., and Ojeda, A. Urticaria induced by caffeine. J.Investig.Allergol.Clin Immunol. 1993;3(3):160-162.
  97. 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
  98. Garrett, B. E. and Griffiths, R. R. Physical dependence increases the relative reinforcing effects of caffeine versus placebo. Psychopharmacology (Berl) 1998;139(3):195-202. PubMed
  99. Lane, J. D. and Phillips-Bute, B. G. Caffeine deprivation affects vigilance performance and mood. Physiol Behav. 1998;65(1):171-175. PubMed
  100. Boekema, P. J., Samsom, M., van Berge Henegouwen, G. P., and Smout, A. J. Coffee and gastrointestinal function: facts and fiction. A review. Scand J Gastroenterol.Suppl 1999;230:35-39. PubMed
  101. Terry, P., Lagergren, J., Wolk, A., and Nyren, O. Reflux-inducing dietary factors and risk of adenocarcinoma of the esophagus and gastric cardia. Nutr Cancer 2000;38(2):186-191.
  102. Pollak, C. P. and Bright, D. Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth-graders. Pediatrics 2003;111(1):42-46. PubMed
  103. DiBaise, J. K. A randomized, double-blind comparison of two different coffee-roasting processes on development of heartburn and dyspepsia in coffee-sensitive individuals. Dig.Dis.Sci 2003;48(4):652-656. PubMed
  104. Wang, J. H., Luo, J. Y., Dong, L., Gong, J., and Tong, M. Epidemiology of gastroesophageal reflux disease: a general population-based study in Xi'an of Northwest China. World J Gastroenterol. 6-1-2004;10(11):1647-1651. PubMed
  105. Naliboff, B. D., Mayer, M., Fass, R., Fitzgerald, L. Z., Chang, L., Bolus, R., and Mayer, E. A. The effect of life stress on symptoms of heartburn. Psychosom.Med 2004;66(3):426-434. PubMed
  106. Massey, L. K. and Sutton, R. A. Acute caffeine effects on urine composition and calcium kidney stone risk in calcium stone formers. J.Urol. 2004;172(2):555-558. PubMed
  107. Tavani, A. and La, Vecchia C. Coffee, decaffeinated coffee, tea and cancer of the colon and rectum: a review of epidemiological studies, 1990-2003. Cancer Causes Control 2004;15(8):743-757. PubMed
  108. Noordzij, M., Uiterwaal, C. S., Arends, L. R., Kok, F. J., Grobbee, D. E., and Geleijnse, J. M. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens. 2005;23(5):921-928. PubMed
  109. Chandrasekaran, S., Rochtchina, E., and Mitchell, P. Effects of caffeine on intraocular pressure: the Blue Mountains Eye Study. J Glaucoma. 2005;14(6):504-507. PubMed
  110. Morgan, J. C. and Sethi, K. D. Drug-induced tremors. Lancet Neurol. 2005;4(12):866-876. PubMed
  111. Doan, B. K., Hickey, P. A., Lieberman, H. R., and Fischer, J. R. Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Aviat.Space Environ Med 2006;77(10):1034-1040.
  112. Whalen, D. J., Silk, J. S., Semel, M., Forbes, E. E., Ryan, N. D., Axelson, D. A., Birmaher, B., and Dahl, R. E. Caffeine consumption, sleep, and affect in the natural environments of depressed youth and healthy controls. J Pediatr.Psychol. 2008;33(4):35 PubMed
  113. 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
  114. Mort, J. R. and Kruse, H. R. Timing of blood pressure measurement related to caffeine consumption. Ann Pharmacother. 2008;42(1):105-110.
  115. Ganmaa, D., Willett, W. C., Li, T. Y., Feskanich, D., van Dam, R. M., Lopez-Garcia, E., Hunter, D. J., and Holmes, M. D. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer 5-1-2008;122(9):2071-2076. PubMed
  116. Killgore, W. D., Rupp, T. L., Grugle, N. L., Reichardt, R. M., Lipizzi, E. L., and Balkin, T. J. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness. J Sleep Res 2008;17(3):3 PubMed
  117. Ozsungur, S., Brenner, D., and El-Sohemy, A. Fourteen well-described caffeine withdrawal symptoms factor into three clusters. Psychopharmacology (Berl) 2009;201(4):541-548. PubMed
  118. Ishitani, K., Lin, J., Manson, J. E., Buring, J. E., and Zhang, S. M. Caffeine consumption and the risk of breast cancer in a large prospective cohort of women. Arch Intern Med 10-13-2008;168(18):2022-2031. PubMed
  119. Tunnicliffe, J. M., Erdman, K. A., Reimer, R. A., Lun, V., and Shearer, J. Consumption of dietary caffeine and coffee in physically active populations: physiological interactions. Appl Physiol Nutr Metab 2008;33(6):1301-1310. PubMed
  120. Sin, C. W., Ho, J. S., and Chung, J. W. Systematic review on the effectiveness of caffeine abstinence on the quality of sleep. J Clin Nurs. 2009;18(1):13-21. PubMed
  121. 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
  122. 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
  123. Killgore, W. D., Kahn-Greene, E. T., Grugle, N. L., Killgore, D. B., and Balkin, T. J. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 2-1-2009;32(2):205-216. PubMed
  124. Natale, F., Cirillo, C., Di Marco, G. M., di Vetta, L. S., Aronne, L., Siciliano, A., Mocerino, R., Tedesco, M. A., Golino, P., and Calabro, R. When chewing gum is more than just a bad habit. Lancet 5-30-2009;373(9678):1918. PubMed
  125. Calamaro, C. J., Mason, T. B., and Ratcliffe, S. J. Adolescents living the 24/7 lifestyle: effects of caffeine and technology on sleep duration and daytime functioning. Pediatrics 2009;123(6):e1005-e1010. PubMed
  126. Koran, L. M., Aboujaoude, E., and Gamel, N. N. Double-blind study of dextroamphetamine versus caffeine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2009;70(11):1530-1535. PubMed
  127. Luebbe, A. M. and Bell, D. J. Mountain Dew or mountain don't?: a pilot investigation of caffeine use parameters and relations to depression and anxiety symptoms in 5th- and 10th-grade students. J Sch Health 2009;79(8):380-387.
  128. Skouroliakou, M., Bacopoulou, F., and Markantonis, S. L. Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial. J Paediatr.Child Health 2009;45(10):587-592. PubMed
  129. Urade, Y. [Molecular mechanisms of insomnia]. Nippon Rinsho 2009;67(8):1489-1493.
  130. Montandon, G., Horner, R. L., Kinkead, R., and Bairam, A. Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats. J Physiol 11-15-2009;587(Pt 22):5493-5507. PubMed
  131. Addicott, M. A. and Laurienti, P. J. A comparison of the effects of caffeine following abstinence and normal caffeine use. Psychopharmacology (Berl) 2009;207(3):423-431. PubMed
  132. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433. PubMed
  133. 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
  134. 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
  135. Attwood, A., Terry, P., and Higgs, S. Conditioned effects of caffeine on performance in humans. Physiol Behav 3-3-2010;99(3):286-293. PubMed
  136. Skinner, T. L., Jenkins, D. G., Coombes, J. S., Taaffe, D. R., and Leveritt, M. D. Dose response of caffeine on 2000-m rowing performance. Med Sci Sports Exerc. 2010;42(3):571-576. PubMed
  137. Holick, C. N., Smith, S. G., Giovannucci, E., and Michaud, D. S. Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies. Cancer Epidemiol.Biomarkers Prev 2010;19(1):39-47. PubMed
  138. 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
  139. 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
  140. 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
  141. Greenwood, D. C., Alwan, N., Boylan, S., Cade, J. E., Charvill, J., Chipps, K. C., Cooke, M. S., Dolby, V. A., Hay, A. W., Kassam, S., Kirk, S. F., Konje, J. C., Potdar, N., Shires, S., Simpson, N., Taub, N., Thomas, J. D., Walker, J., White, K. L., and
  142. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  143. Brick, C. A., Seely, D. L., and Palermo, T. M. Association between sleep hygiene and sleep quality in medical students. Behav Sleep Med 2010;8(2):113-121. PubMed
  144. Digdon, N. L. Circadian preference and college students' beliefs about sleep education. Chronobiol.Int 2010;27(2):297-317. PubMed
  145. Boos, C. J., White, S. H., Bland, S. A., and McAllister, P. D. Dietary supplements and military operations: caution is advised. J R.Army Med Corps 2010;156(1):41-43. PubMed
  146. Casiglia, E., Bongiovi, S., Paleari, C. D., Petucco, S., Boni, M., Colangeli, G., Penzo, M., and Pessina, A. C. Haemodynamic effects of coffee and caffeine in normal volunteers: a placebo-controlled clinical study. J.Intern.Med. 1991;229(6):501-504. PubMed
  147. Aguggia, M. and Saracco, M. G. Pathophysiology of migraine chronification. Neurol.Sci 2010;31 Suppl 1:S15-S17. PubMed
  148. Torelli, P. and Manzoni, G. C. Fasting headache. Curr Pain Headache Rep. 2010;14(4):284-291.
  149. Farag, N. H., Whitsett, T. L., McKey, B. S., Wilson, M. F., Vincent, A. S., Everson-Rose, S. A., and Lovallo, W. R. Caffeine and blood pressure response: sex, age, and hormonal status. J Womens Health (Larchmt.) 2010;19(6):1171-1176. PubMed
  150. 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
  151. Suen, L. K., Tam, W. W., and Hon, K. L. Association of sleep hygiene-related factors and sleep quality among university students in Hong Kong. Hong.Kong.Med.J 2010;16(3):180-185.
  152. Stafford, L. D., Wright, C., and Yeomans, M. R. The drink remains the same: implicit positive associations in high but not moderate or non-caffeine users. Psychol.Addict.Behav. 2010;24(2):274-281. PubMed
  153. 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
  154. Freire, R. C., Perna, G., and Nardi, A. E. Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment. Harv.Rev.Psychiatry 2010;18(4):220-229. PubMed
  155. 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
  156. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  157. Kujawa-Hadrys, M., Tosik, D., and Bartel, H. Changes in thickness of each layer of developing chicken cornea after administration of caffeine. Folia Histochem.Cytobiol. 2010;48(2):273-277. PubMed
  158. Boggs, D. A., Palmer, J. R., Stampfer, M. J., Spiegelman, D., Adams-Campbell, L. L., and Rosenberg, L. Tea and coffee intake in relation to risk of breast cancer in the Black Women's Health Study. Cancer Causes Control 2010;21(11):1941-1948. PubMed
  159. Li, S., Zhu, S., Jin, X., Yan, C., Wu, S., Jiang, F., and Shen, X. Risk factors associated with short sleep duration among Chinese school-aged children. Sleep Med. 2010;11(9):907-916. PubMed
  160. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  161. Knight, J. M., Avery, E. F., Janssen, I., and Powell, L. H. Cortisol and depressive symptoms in a population-based cohort of midlife women. Psychosom.Med. 2010;72(9):855-861. PubMed
  162. Porkka-Heiskanen, T. Methylxanthines and sleep. Handb.Exp.Pharmacol 2011;(200):331-348. PubMed
  163. 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
  164. 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
  165. 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
  166. Duvnjak-Zaknich, D. M., Dawson, B. T., Wallman, K. E., and Henry, G. Effect of caffeine on reactive agility time when fresh and fatigued. Med.Sci.Sports Exerc. 2011;43(8):1523-1530. PubMed
  167. Astorino, T. A., Martin, B. J., Schachtsiek, L., Wong, K., and Ng, K. Minimal effect of acute caffeine ingestion on intense resistance training performance. J Strength.Cond.Res 2011;25(6):1752-1758. PubMed
  168. Kivity, S., Ben Aharon, Y., Man, A., and Topilsky, M. The effect of caffeine on exercise-induced bronchoconstriction. Chest 1990;97(5):1083-1085. PubMed
  169. Lubin, F. and Ron, E. Consumption of methylxanthine-containing beverages and the risk of breast cancer. Cancer Lett. 1990;53(2-3):81-90. PubMed
  170. 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
  171. 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
  172. Birkett, N. J. and Logan, A. G. Caffeine-containing beverages and the prevalence of hypertension. J Hypertens.Suppl 1988;6(4):S620-S622. PubMed
  173. Fraumeni, J. F., Jr., Scotto, J., and Dunham, L. J. Coffee-drinking and bladder cancer. Lancet 11-27-1971;2(7735):1204. PubMed
  174. Greden, J. F. Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry 1974;131(10):1089-1092. PubMed
  175. Whitsett, T. L., Manion, C. V., and Christensen, H. D. Cardiovascular effects of coffee and caffeine. Am.J.Cardiol. 3-15-1984;53(7):918-922. PubMed
  176. Firestone, P., Poitras-Wright, H., and Douglas, V. The effects of caffeine on hyperactive children. J.Learn.Disabil. 1978;11(3):133-141. PubMed
  177. Thomas, F. B., Steinbaugh, J. T., Fromkes, J. J., Mekhjian, H. S., and Caldwell, J. H. Inhibitory effect of coffee on lower esophageal sphincter pressure. Gastroenterology 1980;79(6):1262-1266. DOI
  178. Linn, S., Schoenbaum, S. C., Monson, R. R., Rosner, B., Stubblefield, P. G., and Ryan, K. J. No association between coffee consumption and adverse outcomes of pregnancy. N.Engl.J Med 1-21-1982;306(3):141-145. PubMed
  179. Cohen, S. Pathogenesis of coffee-induced gastrointestinal symptoms. N.Engl.J Med 7-17-1980;303(3):122-124. PubMed
  180. Feldman, M. and Barnett, C. Relationships between the acidity and osmolality of popular beverages and reported postprandial heartburn. Gastroenterology 1995;108(1):125-131. PubMed
  181. Quinlan, P., Lane, J., and Aspinall, L. Effects of hot tea, coffee and water ingestion on physiological responses and mood: the role of caffeine, water and beverage type. Psychopharmacology (Berl) 1997;134(2):164-173. PubMed
  182. Youngstedt, S. D., O'Connor, P. J., Crabbe, J. B., and Dishman, R. K. Acute exercise reduces caffeine-induced anxiogenesis. Med.Sci Sports Exerc. 1998;30(5):740-745. PubMed
  183. Kaminsky, L. A., Martin, C. A., and Whaley, M. H. Caffeine consumption habits do not influence the exercise blood pressure response following caffeine ingestion. J.Sports Med.Phys.Fitness 1998;38(1):53-58.
  184. McManamy, M. C. and Schube, P. G. Caffeine intoxication: report of a case the symptoms of which amounted to a psychosis. New England Journal of Medicine 1936;215:616-620. DOI
  185. Richter, J. E., Katz, P. O., and Waring, J. P. Gastroesophageal Reflux Disease. IFFGD 2000;
  186. Hsu, C., Harden, R. N., and Houle, T. Nicotine and caffeine intake in complex regional pain syndrome. Journal of Back and Musculoskeletal Rehabilitation 2002;16(1):33-38. PubMed
  187. Luebbe, A. M. Child and Adolescent Anxiety Sensitivity, Perceived Subjective Effects of Caffeine and Caffeine Consumption. J Caffeine Res 2011;1(4):213-218. DOI
  188. Li-Neng, Y., Greenstadt, L., and Shapiro, D. Effects of caffeine on blood pressure:A cross-cultural comparison. Psychophysiology 1983;20
  189. Fotherby, M. D., Ghandi, C., Haigh, R. A., Macdonald, T. A., and Potter, J. F. Sustained caffeine use has no pressor effect in the elderly. Cardiology in the Elderly 1994;2(6):499-503.
  190. Basurto Ona X, Uriona Tuma SM, Martínez García L, Solà I, Bonfill Cosp X. Drug therapy for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2013 28;2:CD001792. doi: 10.1002/14651858.CD001792.pub3. Review. PubMed
  191. Beaudoin MS, Allen B, Mazzetti G, Sullivan PJ, Graham TE. Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women. Appl Physiol Nutr Metab. 2013;38(2):140-7. doi: 10.1139/apnm-2012-0201. Epub 2012 9. PubMed
  192. 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
  193. Chen L, Bell EM, Browne ML, Druschel CM, Romitti PA, Schmidt RJ, Burns TL, Moslehi R, Olney RS; National Birth Defects Prevention Study. Maternal caffeine consumption and risk of congenital limb deficiencies. Birth Defects Res A Clin Mol Teratol. 2012 De PubMed
  194. Chen LW, Wu Y, Neelakantan N, Chong MF, Pan A, van Dam RM. Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis. BMC Med. 2014 19;12:174. doi: 10.1186/s12916-014-0174-6 PubMed
  195. 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
  196. 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
  197. Greenwood DC, Thatcher NJ, Ye J, Garrard L, Keogh G, King LG, Cade JE. Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis. Eur J Epidemiol. 2014;29(10):725-34. doi: 10.1007/s10654-014-9944-x. PubMed
  198. 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
  199. Lee SM, Choi NK, Lee BC, Cho KH, Yoon BW, Park BJ. Caffeine-containing medicines increase the risk of hemorrhagic stroke. Stroke. 2013 Aug;44(8):2139-43. doi: 10.1161/STROKEAHA.111.674077. Epub 2013 6. PubMed
  200. 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
  201. Simonin C, Duru C, Salleron J, Hincker P, Charles P, Delval A, Youssov K, Burnouf S, Azulay JP, Verny C, Scherer C, Tranchant C, Goizet C, Debruxelles S, Defebvre L, Sablonnière B, Romon-Rousseaux M, Buée L, Destée A, Godefroy O, Dürr A, Landwehrmeyer B;
  202. Szpak A, Allen D. A case of acute suicidality following excessive caffeine intake. J Psychopharmacol. 2012 Nov;26(11):1502-10. doi: 10.1177/0269881112442788. Epub 2012 2. PubMed
  203. 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
  204. 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
  205. Sheppard SG. A preliminary investigation of ibogaine: case reports and recommendations for further study. J Subst Abuse Treat. 1994 Jul-Aug;11(4):379-85. PubMed
  206. 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
  207. Rhee J, Kim R, Kim Y, et al. Maternal caffeine consumption during pregnancy and risk of low birth weight: a dose-response meta-analysis of observational studies. PLoS One. 2015 Jul 20;10(7):e0132334. PubMed
  208. Zuchinali P, Souza GC, Pimentel M, et al. Short-term effects of high-dose caffeine on cardiac arrhythmias in patients with heart failure: a randomized clinical trial. JAMA Intern Med. 2016 Dec 1;176(12):1752-59. PubMed
  209. Lystrup RM, Leggit JC. Caffeine toxicity due to supplement use in caffeine - naïve individual: a cautionary tale. Mil Med. 2015 Aug;180(8):e936-40. PubMed
  210. Magdalan J, Zawadzki M, Skowronek R, et al. Nonfatal and fata intoxications with pure caffeine - report of three different cases. Forensic Sci Med Pathol. 2017 Sep;13(3):355-58.
  211. Trexler ET, Smith-Ryan AE, Roelofs EJ, Hirsch KR, Persky AM, Mock AG. Effects of coffee and caffeine anhydrous intake during creatine loading. J Strength Cond Res. 2016 May;30(5):1438-46. PubMed
  212. 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
  213. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  214. Wang HR, Woo YS, Bahk WM. Caffeine-induced psychiatric manifestations: a review. Int Clin Psychopharmacol. 2015 Jul;30(4):179-82. PubMed
  215. 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
  216. Vliegenthart R, Miedema M, Hutten GJ, van Kaam AH, Onland W. High versus standard dose caffeine for apnoea: a systematic review. Arch Dis Child Fetal Neonatal Ed 2018;103(6):F523-9. doi: 10.1136/archdischild-2017-313556. PubMed
  217. Modzelewska D, Bellocco R, Elfvin A, et al. Caffeine exposure during pregnancy, small for gestational age birth and neonatal outcome - results from the Norwegian Mother and Child Cohort Study. BMC Pregnancy Childbirth. 2019;19(1):80. PubMed
  218. Shen JG, Brooks MB, Cincotta J, Manjourides JD. Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: A systematic review and meta-analysis. J Sci Med Sport. 2019;22(2):232-238. PubMed
  219. Berglundh S, Vollrath M, Brantsæter AL, et al. Maternal caffeine intake during pregnancy and child neurodevelopment up to eight years of age-Results from the Norwegian Mother, Father and Child Cohort Study. Eur J Nutr. 2020. PubMed
  220. Jin F, Qiao C. Association of maternal caffeine intake during pregnancy with low birth weight, childhood overweight, and obesity: a meta-analysis of cohort studies. Int J Obes (Lond). 2020. PubMed
  221. Krittanawong C, Tunhasiriwet A, Wang Z, et al. Is caffeine or coffee consumption a risk for new-onset atrial fibrillation? A systematic review and meta-analysis. Eur J Prev Cardiol. 2020:2047487320908385. PubMed
  222. Zhang H, Lee ZX, Qiu A. Caffeine intake and cognitive functions in children. Psychopharmacology (Berl). 2020;237(10):3109-3116. PubMed
  223. 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
  224. 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
  225. 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
  226. 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
  227. Hinkle SN, Gleason JL, Yisahak SF, et al. Assessment of Caffeine Consumption and Maternal Cardiometabolic Pregnancy Complications. JAMA Netw Open 2021;4(11):e2133401. PubMed
  228. Yartsev A, Peisah C. Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report. BMC Psychiatry 2021;21(1):192. PubMed
  229. Tinawi M. Severe Rhabdomyolysis Due to Strenuous Exercise With a Potential Role of a High-Caffeine Energy Drink. Cureus 2022;14(1):e20867. PubMed
  230. 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
  231. Ismail RIH, Awad HA, Saber M, Shehata BM. Bone mineral content for preterm neonates treated with caffeine using dual energy X-ray absorptiometry: An observational study. J Neonatal Perinatal Med 2023;16(1):129-135. PubMed
  232. Zhao J, Huang Y, Yu X. Caffeine intake and the risk of incident kidney stones: a systematic review and meta-analysis. Int Urol Nephrol 2022;54(10):2457-2466. PubMed
  233. Abbas-Hashemi SA, Hosseininasab D, Rastgoo S, Shiraseb F, Asbaghi O. The effects of caffeine supplementation on blood pressure in adults: A systematic review and dose-response meta-analysis. Clin Nutr ESPEN 2023;58:165-177. PubMed
  234. Oliphant EA, Hanning SM, McKinlay CJD, Alsweiler JM. Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis. J Perinatol 2024;44(6):785-801. PubMed
  235. Kühne T, Wallace E, Herzig D, et al. Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over tr
  236. Song JJ, Eyabi JC, Awatramani PD, Mitchell BG, Nene SY. Sudden Reduction in Caffeine Intake Increases Serum Lithium Concentration to Supratherapeutic Level: A Case Report. Prim Care Companion CNS Disord 2024;26(2):23cr03642. PubMed

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Ginger 64 references
  1. Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1991;38:19-24. PubMed
  2. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2000;(2):CD000145. PubMed
  3. Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 2001;97:577-82. DOI
  4. Backon J. Ginger in preventing nausea and vomiting of pregnancy; a caveat due to its thromboxane synthetase activity and effect on testosterone binding. Eur J Obstet Gynecol Reprod Biol 1991;42:163-4. PubMed
  5. Srivastava KC. Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids 1989;35:183-5. PubMed
  6. Stewart JJ, Wood MJ, Wood CD, Mims ME. Effects of ginger on motion sickness susceptibility and gastric function. Pharmacology 1991;42:111-20. PubMed
  7. Smith C, Crowther C, Willson K, et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639-45. PubMed
  8. Portnoi G, Chng LA, Karimi-Tabesh L, et al. Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy. Am J Obstet Gynecol 2003;189:1374-7.. PubMed
  9. Wigler I, Grotto I, Caspi D, Yaron M. The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis. Osteoarthritis Cartilage 2003;11:783-9. PubMed
  10. Ghayur MN, Gilani AH. Ginger lowers blood pressure through blockade of voltage-dependent calcium channels. J Cardiovasc Pharmacol 2005;45:74-80. PubMed
  11. Thomson M, Al-Qattan KK, Al-Sawan SM, et al. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot Essent Fatty Acids 2002;67:475-8. PubMed
  12. Kanerva L, Estlander T, Jolanki R. Occupational allergic contact dermatitis from spices. Contact Dermatitis 1996;35:157-62. PubMed
  13. Akhani SP, Vishwakarma SL, Goyal RK. Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats. J Pharm Pharmacol 2004;56:101-5.
  14. Kruth P, Brosi E, Fux R, et al. Ginger-associated overanticoagulation by phenprocoumon. Ann Pharmacother 2004;38:257-60. PubMed
  15. Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005;59:425-32. PubMed
  16. Borrelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol 2005;105:849-56. PubMed
  17. Smith C, Crowther C, Wilson K et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639-45. PubMed
  18. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8. PubMed
  19. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  20. Ozgoli G, Goli M, Moattar F. Comparison of effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea. J Altern Complement Med 2009;15:129-32. PubMed
  21. Black CD, Herring MP, Hurley DJ, O'Connor PJ. Ginger (Zingiber officinale) reduces muscle pain caused by eccentric exercise. J Pain 2010;11:894-903. PubMed
  22. Heitmann K, Nordeng H, Holst L. Safety of ginger use in pregnancy: results from a large population-based cohort study. Eur J Clin Pharmacol 2012 Jun 17. PubMed
  23. Ryan JL, Heckler CE, Roscoe JA, et al. Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients. Support Care Cancer. 2012;20:1479-89. PubMed
  24. Backon J. Ginger as an antiemetic: possible side effects due to its thromboxane synthetase activity. Anaesthesia. 1991;46(8):705-6.. PubMed
  25. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002;27:391-401. PubMed
  26. Argento A, Tiraferri E, Marzaloni M. [Oral anticoagulants and medicinal plants. An emerging interaction]. Ann Ital Med Int. 2000;15:139-43.
  27. Young HY, Liao JC, Chang YS, et al. Synergistic effect of ginger and nifedipine on human platelet aggregation: a study in hypertensive patients and normal volunteers. Am J Chin Med. 2006;34:545-51. PubMed
  28. Greenway FL, Liu Z, Martin CK, et al. Safety and efficacy of NT, an herbal supplement, in treating human obesity. Int J Obes (Lond). 2006;30:1737-41. PubMed
  29. Shalansky S, Lynd L, Richardson K, et al. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27:1237-47. PubMed
  30. Lesho EP, Saullo L, Udvari-Nagy S. A 76-year-old woman with erratic anticoagulation. Cleve Clin J Med. 2004;71:651-6. PubMed
  31. Okonta JM, Uboh M, Obonga WO. Herb-Drug Interaction: A Case Study of Effect of Ginger on the Pharmacokinetic of Metronidazole in Rabbit. Indian Journal of Pharmaceutical Sciences (India) 2008;70(230):232. PubMed
  32. Chiang HM, Chao PD, Hsiu SL, et al. Ginger significantly decreased the oral bioavailability of cyclosporine in rats. Am J Chin Med. 2006;34:845-55. PubMed
  33. Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol. 2005;97:227-30. PubMed
  34. Ojewole JA. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. Phytother Res. 2006;20:764-72.
  35. Al-Amin ZM, Thomson M, Al-Qattan KK, et al. Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. Br J Nutr. 2006;96:660-6.
  36. Islam MS, Choi H. Comparative effects of dietary ginger (Zingiber officinale) and garlic (Allium sativum) investigated in a type 2 diabetes model of rats. J Med Food. 2008;11:152-9.
  37. Cady RK, Goldstein J, Nett R, et al. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache 2011;51:1078-86.
  38. Futrell, J. M. and Rietschel, R. L. Spice allergy evaluated by results of patch tests. Cutis 1993;52(5):288-290.
  39. Sripramote, M. and Lekhyananda, N. A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy. J Med Assoc.Thai. 2003;86(9):846-853.
  40. Lohsiriwat, S., Rukkiat, M., Chaikomin, R., and Leelakusolvong, S. Effect of ginger on lower esophageal sphincter pressure. J.Med.Assoc.Thai. 2010;93(3):366-372.
  41. Liu, P. H. and Ho, H. L. Ginger and drug bezoar induced small bowel obstruction. J R.Coll.Surg.Edinb. 1983;28(6):397-398.
  42. Maghbooli M, Golipour F, Moghimi Esfandabadi A, Yousefi M. Comparison between the efficacy of ginger and sumatriptan in the ablative treatment of the common migraine. Phytother Res 2014;28(3):412-5. PubMed
  43. Mahluji S, Attari VE, Mobasseri M, Payahoo L, Ostadrahimi A, Golzari SE. Effects of ginger (Zingiber officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients. Int J Food Sci Nutr 2013;64(6):682-6.
  44. Mozaffari-Khosravi H, Talaei B, Jalali BA, Najarzadeh A, Mozayan MR. The effect of ginger powder supplementation on insulin resistance and glycemic indices in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Complement PubMed
  45. Paramdeep G. Efficacy and tolerability of ginger (Zingiber officinale) in patients of osteoarthritis of knee. Indian J Physiol Pharmacol 2013;57(2):177-83.
  46. Rahnama P, Montazeri A, Huseini HF, Kianbakht S, Naseri M. Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med 2012;12:92. PubMed
  47. Viljoen E, Visser J, Koen N, Musekiwa A. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J 2014;13:20. PubMed
  48. Bartels EM, Folmer VN, Bliddal H, et al. Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials. Osteoarthritis Cartilage. 2015;23(1):13-21. PubMed
  49. Choi JS, Han JY, Ahn HK, et al. Assessment of fetal and neonatal outcomes in the offspring of women who had been treated with dried ginger (Zingiberis rhizoma siccus) for a variety of illnesses during pregnancy. J Obstet Gynaecol. 2015;35(2):125-30.
  50. Marx W, McKavanagh D, McCarthy AL, Bird R, Ried K, Chan A, Isenring L. The effect of ginger (Zingiber officinale) on platelet aggregation: A systematic literature review. PLoS One. 2015;10(10):e0141119. PubMed
  51. Crichton M, Marshall S, Marx W, McCarthy AL, Isenring E. Efficacy of ginger (Zingiber officinale) in ameliorating chemotherapy-induced nausea and vomiting and chemotherapy-related outcomes: A systematic review update and meta-analysis. J Acad Nutr Diet. 2 PubMed
  52. Martins LB, Rodrigues AMDS, Monteze NM, et al. Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) in the prophylactic treatment of migraine. Cephalalgia. 2020;40(1):88-95.
  53. Martins LB, Rodrigues AMDS, Rodrigues DF, Dos Santos LC, Teixeira AL, Ferreira AVM. Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) addition in migraine acute treatment. Cephalalgia. 2019;39(1):68-76.
  54. Ahad A, Raish M, Bin Jardan YA, Alam MA, Al-Mohizea AM, Al-Jenoobi FI. Effect of Hibiscus sabdariffa and Zingiber officinale on the antihypertensive activity and pharmacokinetic of losartan in hypertensive rats. Xenobiotica. 2020:1-11.
  55. Okuhira H, Nakatani Y, Furukawa F, Kanazawa N. Anaphylaxis to ginger induced by herbal medicine. Allergol Int. 2020;69(1):159-160. PubMed
  56. Yamprasert R, Chanvimalueng W, Mukkasombut N, Itharat A. Ginger extract versus Loratadine in the treatment of allergic rhinitis: a randomized controlled trial. BMC Complement Med Ther. 2020;20(1):116. PubMed
  57. Ebrahimzadeh A, Ebrahimzadeh A, Mirghazanfari SM, Hazrati E, Hadi S, Milajerdi A. The effect of ginger supplementation on metabolic profiles in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. PubMed
  58. Alam MA, Bin Jardan YA, Alzenaidy B, et al. Effect of Hibiscus sabdariffa and Zingiber officinale on pharmacokinetics and pharmacodynamics of amlodipine. J Pharm Pharmacol 2021;73(9):1151-60.
  59. Akbarzadeh E, Heydari M, Atarzadeh F, Jaladat AM. Chronic dysuria following ginger (Zingiber officinale) use: a case report. Galen Med J 2018;7:e1086. DOI
  60. 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
  61. Rostamkhani H, Veisi P, Niknafs B, Jafarabadi MA, Ghoreishi Z. The effect of zingiber officinale on prooxidant-antioxidant balance and glycemic control in diabetic patients with ESRD undergoing hemodialysis: a double-blind randomized control trial. BMC Co PubMed
  62. Husain I, Dale OR, Idrisi M, et al. Evaluation of the Herb-Drug Interaction (HDI) Potential of Zingiber officinale and Its Major Phytoconstituents. J Agric Food Chem. 2023;71(19):7521-7534.
  63. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed
  64. 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

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Capsicum 89 references
  1. Covington TR, et al. Handbook of Nonprescription Drugs. 11th ed. Washington, DC: American Pharmaceutical Association, 1996.
  2. Cooper RL, Cooper MM. Red pepper-induced dermatitis in breast-fed infants. Dermatol 1996;93:61-2. PubMed
  3. Millqvist E. Cough provocation with capsaicin is an objective way to test sensory hyperreactivity in patients with asthma-like symptoms. Allergy 2000;55:546-50. DOI
  4. Locock RA. Capsicum. Can Pharm J 1985;118:517-9.
  5. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 2004;328:991. PubMed
  6. Schmulson MJ, Valdovinos MA, Milke P. Chili pepper and rectal hyperalgesia in irritable bowel syndrome. Am J Gastroenterol 2003;98:1214-5. PubMed
  7. Surh YJ, Lee SS. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? Food Chem Toxicol 1996;34:313-6. PubMed
  8. Bouraoui A, Brazier JL, Zouaghi H, Rousseau M. Theophylline pharmacokinetics and metabolism in rabbits following single and repeated administration of Capsicum fruit. Eur J Drug Metab Pharmacokinet 1995;20:173-8.
  9. Hogaboam CM, Wallace JL. Inhibition of platelet aggregation by capsaicin. An effect unrelated to actions on sensory afferent neurons. Eur J Pharmacol 1991;202:129-31. PubMed
  10. Wang JP, Hsu MF, Teng CM. Antiplatelet effect of capsaicin. Thromb Res 1984;36:497-507. PubMed
  11. Williams SR, Clark RF, Dunford JV. Contact dermatitis associated with capsaicin: Hunan hand syndrome. Ann Emerg Med 1995;25:713-5. PubMed
  12. Zollman TM, Bragg RM, Harrison DA. Clinical effects of oleoresin capsicum (pepper spray) on the human cornea and conjunctiva. Ophthalmology 2000;107:2186-9. PubMed
  13. Bortolotti M, Coccia G, Grossi G, Miglioli M. The treatment of functional dyspepsia with red pepper. Aliment Pharmacol Ther 2002;16:1075-82. PubMed
  14. Hakas JF Jr. Topical capsaicin induces cough in patient receiving ACE inhibitor. Ann Allergy 1990;65:322-3.
  15. Rapoport AM, Bigal ME, Tepper SJ, Sheftell FD. Intranasal medications for the treatment of migraine and cluster headache. CNS Drugs 2004;18:671-85. PubMed
  16. Stjarne P, Rinder J, Heden-Blomquist E, et al. Capsaicin desensitization of the nasal mucosa reduces symptoms upon allergen challenge in patients with allergic rhinitis. Acta Otolaryngol 1998;118:235-9. PubMed
  17. Levy RL. Intranasal capsaicin for acute abortive treatment of migraine without aura. Headache 1995;35:277.
  18. Fusco BM, Marabini S, Maggi CA, et al. Preventative effect of repeated nasal applications of capsaicin in cluster headache. Pain 1994;59:321-5. PubMed
  19. Sicuteri F, Fusco BM, Marabini S, et al. Beneficial effect of capsaicin application to the nasal mucosa in cluster headache. Clin J Pain 1989;5:49-53. PubMed
  20. Marabini S, Ciabatti PG, Polli G, et al. Beneficial effects of intranasal applications of capsaicin in patients with vasomotor rhinitis. Eur Arch Otorhinolaryngol 1991;248:191-4. PubMed
  21. Frerick H, Keitel W, Kuhn U, et al. Topical treatment of chronic low back pain with a capsicum plaster. Pain 2003;106:59-64. PubMed
  22. Keitel W, Frerick H, Kuhn U, et al. Capsicum pain plaster in chronic non-specific low back pain. Arzneimittelforschung 2001;51:896-903. PubMed
  23. Shalansky S, Lynd L, Richardson K, et al. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27:1237-47. PubMed
  24. Sumano-López H, Gutiérrez-Olvera L, Aguilera-Jiménez R, et al. Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations. Arzneimittelforschung. 2007;57(5):286-90. PubMed
  25. Wanwimolruk S, Nyika S, Kepple M, et al. Effects of capsaicin on the pharmacokinetics of antipyrine, theophylline and quinine in rats. J Pharm Pharmacol. 1993;45(7):618-21. PubMed
  26. Cruz L, Castañeda-Hernández G, Navarrete A. Ingestion of chilli pepper (Capsicum annuum) reduces salicylate bioavailability after oral asprin administration in the rat. Can J Physiol Pharmacol.
  27. Rodriguez-Stanley, S., Collings, K. L., Robinson, M., Owen, W., and Miner, P. B., Jr. The effects of capsaicin on reflux, gastric emptying and dyspepsia. Aliment.Pharmacol.Ther. 2000;14(1):129-134. PubMed
  28. Brown, L., Takeuchi, D., and Challoner, K. Corneal abrasions associated with pepper spray exposure. Am.J.Emerg.Med. 2000;18(3):271-272. PubMed
  29. Vesaluoma, M., Muller, L., Gallar, J., Lambiase, A., Moilanen, J., Hack, T., Belmonte, C., and Tervo, T. Effects of oleoresin capsicum pepper spray on human corneal morphology and sensitivity. Invest Ophthalmol.Vis.Sci. 2000;41(8):2138-2147.
  30. Stam, C., Bonnet, M. S., and van Haselen, R. A. The efficacy and safety of a homeopathic gel in the treatment of acute low back pain: a multi-centre, randomised, double-blind comparative clinical trial. Br Homeopath J 2001;90(1):21-28. PubMed
  31. Olajos, E. J. and Salem, H. Riot control agents: pharmacology, toxicology, biochemistry and chemistry. J.Appl.Toxicol. 2001;21(5):355-391. PubMed
  32. Fett, D. D. Botanical briefs: Capsicum peppers. Cutis 2003;72(1):21-23.
  33. McCarthy, G. M. and McCarty, D. J. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J.Rheumatol. 1992;19(4):604-607.
  34. Chaiyata, P., Puttadechakum, S., and Komindr, S. Effect of chili pepper (Capsicum frutescens) ingestion on plasma glucose response and metabolic rate in Thai women. J.Med.Assoc.Thai. 2003;86(9):854-860.
  35. Petruzzi, M., Lauritano, D., De Benedittis, M., Baldoni, M., and Serpico, R. Systemic capsaicin for burning mouth syndrome: short-term results of a pilot study. J.Oral Pathol.Med. 2004;33(2):111-114. PubMed
  36. Misra, M. N., Pullani, A. J., and Mohamed, Z. U. Prevention of PONV by acustimulation with capsicum plaster is comparable to ondansetron after middle ear surgery: [La prevention des NVPO par acustimulation avec un emplatre de Capsicum est comparable a ce PubMed
  37. Milke, P., Diaz, A., Valdovinos, M. A., and Moran, S. Gastroesophageal reflux in healthy subjects induced by two different species of chilli (Capsicum annum). Dig.Dis. 2006;24(1-2):184-188.
  38. de Jong, N. W., van der Steen, J. J., Smeekens, C. C., Blacquiere, T., Mulder, P. G., van Wijk, R. G., and de Groot, H. Honeybee interference as a novel aid to reduce pollen exposure and nasal symptoms among greenhouse workers allergic to sweet bell pepp
  39. Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin.
  40. Tandan, R., Lewis, G. A., Krusinski, P. B., Badger, G. B., and Fries, T. J. Topical capsaicin in painful diabetic neuropathy. Controlled study with long-term follow-up. Diabetes Care 1992;15(1):8-14. PubMed
  41. Gupta, P. J. Red hot chilli consumption is harmful in patients operated for anal fissure - a randomized, double-blind, controlled study. Dig.Surg. 2007;24(5):354-357. PubMed
  42. Patane, S., Marte, F., Di Bella, G., Cerrito, M., and Coglitore, S. Capsaicin, arterial hypertensive crisis and acute myocardial infarction associated with high levels of thyroid stimulating hormone. Int.J Cardiol. 5-1-2009;134(1):130-132. PubMed
  43. Gupta, P. J. Consumption of red-hot chili pepper increases symptoms in patients with acute anal fissures. A prospective, randomized, placebo-controlled, double blind, crossover trial. Arq Gastroenterol. 2008;45(2):124-127. PubMed
  44. Gupta, P. J. Consumption of red-hot chili pepper increases symptoms in patients with acute anal fissures. Ann.Ital.Chir 2008;79(5):347-351.
  45. Patane, S., Marte, F., La Rosa, F. C., and La, Rocca R. Capsaicin and arterial hypertensive crisis. Int J Cardiol. 10-8-2010;144(2):e26-e27. PubMed
  46. Chaiyasit, K., Khovidhunkit, W., and Wittayalertpanya, S. Pharmacokinetic and the effect of capsaicin in Capsicum frutescens on decreasing plasma glucose level. J Med.Assoc.Thai. 2009;92(1):108-113.
  47. Blanc, P., Liu, D., Juarez, C., and Boushey, H. A. Cough in hot pepper workers. Chest 1991;99(1):27-32. PubMed
  48. Akcay, A. B., Ozcan, T., Seyis, S., and Acele, A. Coronary vasospasm and acute myocardial infarction induced by a topical capsaicin patch. Turk.Kardiyol.Dern.Ars 2009;37(7):497-500.
  49. van Boxel, O. S., ter Linde, J. J., Siersema, P. D., and Smout, A. J. Role of chemical stimulation of the duodenum in dyspeptic symptom generation. Am J Gastroenterol. 2010;105(4):803-811. PubMed
  50. Niemcunowicz-Janica, A., Ptaszynska-Sarosiek, I., and Wardaszka, Z. [Sudden death caused by an oleoresin capsicum spray]. Arch.Med.Sadowej.Kryminol. 2009;59(3):252-254.
  51. Reuter, J., Merfort, I., and Schempp, C. M. Botanicals in dermatology: an evidence-based review. Am J Clin Dermatol 2010;11(4):247-267. PubMed
  52. McCormack, P. L. Capsaicin dermal patch: in non-diabetic peripheral neuropathic pain. Drugs 10-1-2010;70(14):1831-1842. PubMed
  53. Bortolotti, M. and Porta, S. Effect of red pepper on symptoms of irritable bowel syndrome: preliminary study. Dig.Dis.Sci 2011;56(11):3288-3295. PubMed
  54. Webster, L. R., Peppin, J. F., Murphy, F. T., Lu, B., Tobias, J. K., and Vanhove, G. F. Efficacy, safety, and tolerability of NGX-4010, capsaicin 8% patch, in an open-label study of patients with peripheral neuropathic pain. Diabetes Res Clin Pract. 2011 PubMed
  55. Gerber, S., Frueh, B. E., and Tappeiner, C. Conjunctival proliferation after a mild pepper spray injury in a young child. Cornea 2011;30(9):1042-1044. PubMed
  56. Lim, L. G., Tay, H., and Ho, K. Y. Curry induces acid reflux and symptoms in gastroesophageal reflux disease. Dig.Dis.Sci 2011;56(12):3546-3550. PubMed
  57. Ludy, M. J., Moore, G. E., and Mattes, R. D. The effects of capsaicin and capsiate on energy balance: critical review and meta-analyses of studies in humans. Chem Senses 2012;37(2):103-121. PubMed
  58. Sayin, M. R., Karabag, T., Dogan, S. M., Akpinar, I., and Aydin, M. A case of acute myocardial infarction due to the use of cayenne pepper pills. Wien.Klin.Wochenschr. 2012;124(7-8):285-287. PubMed
  59. Bley, K., Boorman, G., Mohammad, B., McKenzie, D., and Babbar, S. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol.Pathol. 2012;40(6):847-873. PubMed
  60. Derry, S. and Moore, R. A. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane.Database.Syst.Rev. 2012;9:CD010111. PubMed
  61. Tominack, R. L. and Spyker, D. A. Capsicum and capsaicin--a review: case report of the use of hot peppers in child abuse. J.Toxicol.Clin.Toxicol. 1987;25(7):591-601. PubMed
  62. Schuurs, A. H., Abraham-Inpijn, L., van Straalen, J. P., and Sastrowijoto, S. H. An unusual case of black teeth. Oral Surg.Oral Med.Oral Pathol. 1987;64(4):427-431. PubMed
  63. Kumar, N., Vij, J. C., Sarin, S. K., and Anand, B. S. Do chillies influence healing of duodenal ulcer? Br.Med.J.(Clin.Res.Ed) 6-16-1984;288(6433):1803-1804. PubMed
  64. Steffee, C. H., Lantz, P. E., Flannagan, L. M., Thompson, R. L., and Jason, D. R. Oleoresin capsicum (pepper) spray and "in-custody deaths". Am.J.Forensic Med.Pathol. 1995;16(3):185-192. PubMed
  65. Knight, T. E. and Hayashi, T. Solar (brachioradial) pruritus--response to capsaicin cream. Int.J.Dermatol. 1994;33(3):206-209. DOI
  66. Watson, W. A., Stremel, K. R., and Westdorp, E. J. Oleoresin capsicum (Cap-Stun) toxicity from aerosol exposure. Ann.Pharmacother. 1996;30(7-8):733-735. PubMed
  67. Busker, R. W. and van Helden, H. P. Toxicologic evaluation of pepper spray as a possible weapon for the Dutch police force: risk assessment and efficacy. Am.J.Forensic Med.Pathol. 1998;19(4):309-316. PubMed
  68. Sausenthaler, S., Koletzko, S., Schaaf, B., Lehmann, I., Borte, M., Herbarth, O., von Berg, A., Wichmann, H. E., and Heinrich, J. Maternal diet during pregnancy in relation to eczema and allergic sensitization in the offspring at 2 y of age. Am J Clin Nu PubMed
  69. Bleuel I, Zinkernagel M, Tschopp M, Tappeiner C. Association of bilateral acute anterior uveitis with a capsaicin patch. Ocul Immunol Inflamm 2013;21(5):394-5. PubMed
  70. Casanueva B, Rodero B, Quintial C, Llorca J, González-Gay MA. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients. Rheumatol Int 2013;33(10):2665-70. PubMed
  71. Copeland S, Nugent K. Persistent respiratory symptoms following prolonged capsaicin exposure. Int J Occup Environ Med. 2013;4(4):211-5.
  72. García-Menaya JM, Cordobés -Durán C, Bobadilla-González P, et al. Anaphylactic reaction to bell pepper (Capsicum annuum) in a patient with a latex-fruit syndrome. Allergol Immunopathol (Madr). 2014;42(3):263-5. PubMed
  73. Kim DH, Yoon KB, Park S, et al. Comparison of NSAID patch given as monotherapy and NSAID patch in combination with transcutaneous electric nerve stimulation, a heating pad, or topical capsaicin in the treatment of patients with myofascial pain syndrome o
  74. Kulkantrakorn K, Lorsuwansiri C, Meesawatsom P. 0.025% capsaicin gel for the treatment of painful diabetic neuropathy: a randomized, double-blind, crossover, placebo-controlled trial. Pain Pract. 2013;13(6):497-503. PubMed
  75. Pabalan N, Jarjanazi H, Ozcelik H. The impact of capsaicin intake on risk of developing gastric cancers: a meta-analysis. J Gastrointest Cancer. 2014;45(3):334-41. PubMed
  76. Sandor B, Papp J, Mozsik G, et al. Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination). Acta Physiol Hung. 2014 Dec;101(4):429-37. PubMed
  77. Van Nooten F, Treur M, Pantiri K, Stoker M, Charokopou M. Capsaicin 8% patch versus oral neuropathic pain medications for the treatment of painful diabetic peripheral neuropathy: a systematic literature review and network meta-analysis. Clin Ther. 2017 Ap PubMed
  78. Simpson DM, Robinson-Papp J, Van J, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. J Pain. 2017 Jan;18(1):42-53. PubMed
  79. Campbell CM, Diamond E, Schmidt WK, et al. A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton's neuroma. Pain. 2016 Jun;157(6):1297-304. PubMed
  80. Jorgensen MR, Pedersen AM. Analgesic effect of topical oral capsaicin gel in burning mouth syndrome. Acta Odontol Scand. 2017 Mar;75(2):130-6.
  81. Yuan LJ, Qin Y, Wang L, et al. Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns. Clin PubMed
  82. Dean DJ, Sabagha N, Rose K, et al. A pilot trial of topical capsaicin cream for treatment of cannabinoid hyperemesis syndrome. Acad Emerg Med. 2020;27(11):1166-1172. PubMed
  83. Jang HH, Lee J, Lee SH, Lee YM. Effects of Capsicum annuum supplementation on the components of metabolic syndrome: a systematic review and meta-analysis. Sci Rep. 2020;10(1):20912. PubMed
  84. Joseph MSc A, John PhD F, Thomas MSc JV, Sivadasan SDP, Maliakel PhD B, Mohan PhD R, I M K. Influence of a novel food-grade formulation of red chili extract (Capsicum annum) on overweight subjects: Randomized, double-blinded, placebo-controlled study. J D
  85. Kocak AO, Dogruyol S, Akbas I, et al. Comparison of topical capsaicin and topical piroxicam in the treatment of acute trauma-induced pain: A randomized double-blind trial. Am J Emerg Med. 2020;38(9):1767-1771. PubMed
  86. Lassen CL, Meyer K, Bredthauer A, Klier TW. Facial and oral cross-contamination of a 3-year-old child with high concentration capsaicin: A case report. A A Pract. 2020;14(9):e01258. PubMed
  87. Predel HG, Ebel-Bitoun C, Peil B, Weiser TW, Lange R. Efficacy and safety of diclofenac?+?capsaicin gel in patients with acute back/neck pain: A multicenter randomized controlled study. Pain Ther. 2020;9(1):279-296. PubMed
  88. Umigai N, Kozai Y, Saito T, Takara T. Effects of paprika carotenoid supplementation on bone turnover in postmenopausal women: a randomized, double-blind, placebo-controlled, parallel-group comparison study. Food Nutr Res. 2020;64. PubMed
  89. Trin K, Perino J, Allouchery M, Géniaux H, Miremont G, Salvo F. Second-degree burn induced by high-concentration topical capsaicin with mobility sequelae: A case report. Pain Pract 2023;23(2):216-219. PubMed

See these in context on the Capsicum monograph →

Cola Nut 157 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  8. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  9. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  10. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  11. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  12. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  13. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  14. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  15. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed
  16. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  17. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. PubMed
  18. Weisburger JH. Tea and health: the underlying mechanisms. Proc Soc Exp Biol Med 1999;220:271-5. PubMed
  19. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  20. 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
  21. Tobias JD. Caffeine in the treatment of apnea associated with respiratory syncytial virus infection in neonates and infants. South Med J 2000;93:297-304. DOI
  22. 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
  23. 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
  24. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  25. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  26. 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
  27. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  34. 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
  35. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  36. Dreher HM. The effect of caffeine reduction on sleep quality and well-being in persons with HIV. J Psychosom Res 2003;54:191-8.. PubMed
  37. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  38. Schechter MD, Timmons GD. Objectively measured hyperactivity--II. Caffeine and amphetamine effects. J Clin Pharmacol 1985;25:276-80.. PubMed
  39. 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
  40. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  41. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  42. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  43. 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
  44. 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
  45. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  46. 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
  47. 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
  48. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  49. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  50. 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
  51. 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.
  52. 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
  53. 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
  54. Benton D, Donohoe RT, Sillance B, Nabb S. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci 2001;4:169-78. PubMed
  55. 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
  56. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  57. 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
  58. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  59. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  60. 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
  61. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  62. 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.
  63. 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
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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.
  69. 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
  70. 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
  71. 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.
  72. 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
  73. 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.
  74. 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
  75. 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
  76. 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.
  77. 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
  78. 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.
  79. Kot M, Daniel WA. Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep 2008;60:789-97.
  80. 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
  81. 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
  82. 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.
  83. 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
  84. 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
  85. 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
  86. 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
  87. 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.
  88. 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.
  89. Satoh, E., Ishii, T., Shimizu, Y., Sawamura, S., and Nishimura, M. Black tea extract, thearubigin fraction, counteract the effects of botulinum neurotoxins in mice. Br.J Pharmacol. 2001;132(4):797-798.
  90. Griffiths, R. R. and Chausmer, A. L. Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Nihon Shinkei Seishin Yakurigaku Zasshi 2000;20(
  91. Adams, B. A. and Brubaker, R. F. Caffeine has no clinically significant effect on aqueous humor flow in the normal human eye. Ophthalmology 1990;97(8):1030-1031. PubMed
  92. Davis, R. H. Does caffeine ingestion affect intraocular pressure?. Ophthalmology 1989;96(11):1680-1681. PubMed
  93. Higginbotham, E. J., Kilimanjaro, H. A., Wilensky, J. T., Batenhorst, R. L., and Hermann, D. The effect of caffeine on intraocular pressure in glaucoma patients. Ophthalmology 1989;96(5):624-626.
  94. Wrenn, K. D. and Oschner, I. Rhabdomyolysis induced by a caffeine overdose. Ann.Emerg.Med. 1989;18(1):94-97. PubMed
  95. Stillner, V., Popkin, M. K., and Pierce, C. M. Caffeine-induced delirium during prolonged competitive stress. Am.J.Psychiatry 1978;135(7):855-856. PubMed
  96. 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
  97. Chandrasekaran, S., Rochtchina, E., and Mitchell, P. Effects of caffeine on intraocular pressure: the Blue Mountains Eye Study. J Glaucoma. 2005;14(6):504-507. PubMed
  98. Doan, B. K., Hickey, P. A., Lieberman, H. R., and Fischer, J. R. Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Aviat.Space Environ Med 2006;77(10):1034-1040.
  99. Whalen, D. J., Silk, J. S., Semel, M., Forbes, E. E., Ryan, N. D., Axelson, D. A., Birmaher, B., and Dahl, R. E. Caffeine consumption, sleep, and affect in the natural environments of depressed youth and healthy controls. J Pediatr.Psychol. 2008;33(4):35 PubMed
  100. 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
  101. Killgore, W. D., Rupp, T. L., Grugle, N. L., Reichardt, R. M., Lipizzi, E. L., and Balkin, T. J. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness. J Sleep Res 2008;17(3):3 PubMed
  102. 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
  103. 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
  104. Killgore, W. D., Kahn-Greene, E. T., Grugle, N. L., Killgore, D. B., and Balkin, T. J. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 2-1-2009;32(2):205-216. PubMed
  105. Natale, F., Cirillo, C., Di Marco, G. M., di Vetta, L. S., Aronne, L., Siciliano, A., Mocerino, R., Tedesco, M. A., Golino, P., and Calabro, R. When chewing gum is more than just a bad habit. Lancet 5-30-2009;373(9678):1918. PubMed
  106. Koran, L. M., Aboujaoude, E., and Gamel, N. N. Double-blind study of dextroamphetamine versus caffeine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2009;70(11):1530-1535. PubMed
  107. Luebbe, A. M. and Bell, D. J. Mountain Dew or mountain don't?: a pilot investigation of caffeine use parameters and relations to depression and anxiety symptoms in 5th- and 10th-grade students. J Sch Health 2009;79(8):380-387.
  108. Skouroliakou, M., Bacopoulou, F., and Markantonis, S. L. Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial. J Paediatr.Child Health 2009;45(10):587-592. PubMed
  109. Addicott, M. A. and Laurienti, P. J. A comparison of the effects of caffeine following abstinence and normal caffeine use. Psychopharmacology (Berl) 2009;207(3):423-431. PubMed
  110. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433. PubMed
  111. 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
  112. 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
  113. Attwood, A., Terry, P., and Higgs, S. Conditioned effects of caffeine on performance in humans. Physiol Behav 3-3-2010;99(3):286-293. PubMed
  114. 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
  115. 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
  116. 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
  117. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  118. Boos, C. J., White, S. H., Bland, S. A., and McAllister, P. D. Dietary supplements and military operations: caution is advised. J R.Army Med Corps 2010;156(1):41-43. PubMed
  119. 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
  120. Suen, L. K., Tam, W. W., and Hon, K. L. Association of sleep hygiene-related factors and sleep quality among university students in Hong Kong. Hong.Kong.Med.J 2010;16(3):180-185.
  121. Stafford, L. D., Wright, C., and Yeomans, M. R. The drink remains the same: implicit positive associations in high but not moderate or non-caffeine users. Psychol.Addict.Behav. 2010;24(2):274-281. PubMed
  122. 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
  123. Freire, R. C., Perna, G., and Nardi, A. E. Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment. Harv.Rev.Psychiatry 2010;18(4):220-229. PubMed
  124. 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
  125. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  126. Li, S., Zhu, S., Jin, X., Yan, C., Wu, S., Jiang, F., and Shen, X. Risk factors associated with short sleep duration among Chinese school-aged children. Sleep Med. 2010;11(9):907-916. PubMed
  127. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  128. 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
  129. 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
  130. 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
  131. Birkett, N. J. and Logan, A. G. Caffeine-containing beverages and the prevalence of hypertension. J Hypertens.Suppl 1988;6(4):S620-S622. PubMed
  132. Greden, J. F. Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry 1974;131(10):1089-1092. 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. Browning, D. J. West African crystalline maculopathy. Ophthalmology 2004;111(5):921-925. PubMed
  135. Holcombe, C., Omotara, B. A., Padonu, M. K., and Bassi, A. P. The prevalence of symptoms of dyspepsia in north eastern Nigeria. A random community based survey. Trop.Geogr.Med 1991;43(1-2):209-214.
  136. Holcombe, C., Kaluba, J., and Lucas, S. B. Non-ulcer dyspepsia in Nigeria: a case-control study. Trans.R.Soc Trop.Med Hyg. 1991;85(4):553-555. PubMed
  137. Ibu, J. O., Iyama, A. C., Ijije, C. T., Ishmael, D., Ibeshi, M., and Nwokediuko, S. The effect of cola acuminata and cola nitida on gastric acid secretion. Scand J Gastroenterol Suppl 1986;124:39-45. PubMed
  138. Ogunremi OO and Mamora AO. Cola acuminata (Kolanut) and coffee: Acute effects on sleep of Nigerians. Psychopathologie Africaine 1980;16(1):69-75.
  139. Beaudoin MS, Allen B, Mazzetti G, Sullivan PJ, Graham TE. Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women. Appl Physiol Nutr Metab. 2013;38(2):140-7. doi: 10.1139/apnm-2012-0201. Epub 2012 9. PubMed
  140. 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
  141. Chen LW, Wu Y, Neelakantan N, Chong MF, Pan A, van Dam RM. Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis. BMC Med. 2014 19;12:174. doi: 10.1186/s12916-014-0174-6 PubMed
  142. 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
  143. Greenwood DC, Thatcher NJ, Ye J, Garrard L, Keogh G, King LG, Cade JE. Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis. Eur J Epidemiol. 2014;29(10):725-34. doi: 10.1007/s10654-014-9944-x. PubMed
  144. 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
  145. 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
  146. 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
  147. Rhee J, Kim R, Kim Y, et al. Maternal caffeine consumption during pregnancy and risk of low birth weight: a dose-response meta-analysis of observational studies. PLoS One. 2015 Jul 20;10(7):e0132334. PubMed
  148. Lystrup RM, Leggit JC. Caffeine toxicity due to supplement use in caffeine - naïve individual: a cautionary tale. Mil Med. 2015 Aug;180(8):e936-40. PubMed
  149. 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
  150. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  151. 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
  152. Shen JG, Brooks MB, Cincotta J, Manjourides JD. Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: A systematic review and meta-analysis. J Sci Med Sport. 2019;22(2):232-238. 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. 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
  155. 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
  156. 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
  157. Gleason JL, Sundaram R, Mitro SD, et al. Association of maternal caffeine consumption during pregnancy with child growth. JAMA Netw Open. 2022;5(10):e2239609. PubMed

See these in context on the Cola Nut monograph →

Panax Ginseng 66 references
  1. Scaglione F, Cattaneo G, Alessandria M, Cogo R. Efficacy and safety of the standardized Ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold. Drugs Exp Clin Res 1996;22:65-72.
  2. Palmer BV, Montgomery AC, Monteiro JC, et al. Gin Seng and mastalgia [letter]. BMJ 1978;1:1284. PubMed
  3. Hopkins MP, Androff L, Benninghoff AS. Ginseng face cream and unexplained vaginal bleeding. Am J Obstet Gynecol 1988;159:1121-2. PubMed
  4. Greenspan EM. Ginseng and vaginal bleeding [letter]. JAMA 1983;249:2018.
  5. Gonzalez-Seijo JC, Ramos YM, Lastra I. Manic episode and ginseng: Report of a possible case. J Clin Psychopharmacol 1995;15:447-8.
  6. Dega H, Laporte JL, Frances C, et al. Ginseng as a cause of Stevens-Johnson syndrome. Lancet 1996;347:1344.
  7. Hamid S, Rojter S, Vierling J. Protracted cholestatic hepatitis after the use of Prostata. Ann Intern Med 1997;127:169-70.
  8. Shader RI, Greenblatt DJ. Phenelzine and the dream machine-ramblings and reflections. J Clin Psychopharmacol 1985;5:65. PubMed
  9. Jones BD, Runikis AM. Interaction of ginseng with phenelzine. J Clin Psychopharmacol 1987;7:201-2. PubMed
  10. Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997;54:692-3. PubMed
  11. Becker BN. Ginseng-induced diuretic resistance. JAMA 1996;276:606-7. PubMed
  12. Gurley BJ, Gardner SF, Hubbard MA. Clinical assessment of potential cytochrome P450-mediated herb-drug interactions. AAPS Ann Mtg & Expo Indianapolis, IN: 2000; Oct 29 - Nov 2:presentation #3460.
  13. Park HJ, Lee JH, Song YB, Park KH. Effects of dietary supplementation of lipophilic fraction from Panax ginseng on cGMP and cAMP in rat platelets and on blood coagulation. Biol Pharm Bull 1996;19:1434-9. PubMed
  14. Zhu M, Chan KW, Ng LS, et al. Possible influences of ginseng on the pharmacodynamics of warfarin in rats. J Pharm Pharmacol 1999;51:175-80.
  15. Choi HK, Jung GW, Moon KH, et al. Clinical study of SS-Cream in patients with lifelong premature ejaculation. Urology 2000;55:257-61. PubMed
  16. Shin HR, Kim JY, Yun TK, et al. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control 2000;11:565-76. PubMed
  17. Siegel RK. Ginseng Abuse Syndrome. JAMA 1979;241:1614-5. DOI
  18. Palop-Larrea V, Gonzalvez-Perales JL, Catalan-Oliver C, et al. Metrorrhagia and ginseng. Ann Pharmacother 2000;34:1347-8. PubMed
  19. Caron MF, Hotsko AL, Robertson S, et al. Electrocardiographic and hemodynamic effects of Panax ginseng. Ann Pharmacother 2002;36:758-63..
  20. Eagon PK, Elm MS, Hunter DS, et al. Medicinal herbs: modulation of estrogen action. Era of Hope Mtg, Dept Defense; Breast Cancer Res Prog, Atlanta, GA 2000;Jun 8-11.
  21. Chan LY, Chiu PY, Lau TK. An in-vitro study of ginsenoside Rb(1)-induced teratogenicity using a whole rat embryo culture model. Hum Reprod 2003;18:2166-8..
  22. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87.. PubMed
  23. Wiklund IK, Mattsson LA, Lindgren R, et al. Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Int J Clin Pharmacol Res 1999;19:89-99..
  24. Hammond TG, Whitworth JA. Adverse reactions to ginseng [letter]. Med J Aust 1981;1:492.. PubMed
  25. Punnonen R, Lukola A. Oestrogen-like effect of ginseng. Br Med J 1980;281:1110.. PubMed
  26. Lee YJ, Jin YR, Lim WC, et al. Ginsenoside-Rb1 acts as a weak phytoestrogen in MCF-7 human breast cancer cells. Arch Pharm Res 2003;26:58-63.. PubMed
  27. Xu QF, Fang XL, Chen DF. Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. J Ethnopharmacol 2003;84:187-92. PubMed
  28. Jiang X, Williams KM, Liauw WS, et al. Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004;57:592-9. PubMed
  29. Yun YP, Do JH, Ko SR, et al. Effects of Korean red ginseng and its mixed prescription on the high molecular weight dextran-induced blood stasis in rats and human platelet aggregation. J Ethnopharmacol 2001;77:259-64. PubMed
  30. Wiwanikit V, Taungjarwinai W. A case report of suspected ginseng allergy. Medscape General Medicine 6 (3), 2004. Available at: www.medscape.com/viewarticle/482833 (Accessed 17 September 2004).
  31. Kabalak AA, Soyal OB, Urfalioglu A, et al. Menometrorrhagia and tachyarrhythmia after using oral and topical ginseng. J Womens Health (Larchmt) 2004;13:830-3. PubMed
  32. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8. PubMed
  33. Lee SH, Ahn YM, Ahn SY, et al. Interaction between warfarin and Panax ginseng in ischemic stroke patients. J Altern Complement Med 2008;14:715-721.
  34. Smith M, Lin KM, and Zheng YP. PIII-89 an open trial of nifedipine-herb interactions: Nifedipine with St. John's wort, ginseng or ginkgo biloba. Clin Pharm Ther 2001;69:P86.
  35. Mateo-Carrasco, H., Galvez-Contreras, M. C., Fernandez-Gines, F. D., and Nguyen, T. V. Elevated liver enzymes resulting from an interaction between Raltegravir and Panax ginseng: a case report and brief review. Drug Metabol.Drug Interact. 2012;27(3):171-1
  36. Oh, K. J., Chae, M. J., Lee, H. S., Hong, H. D., and Park, K. Effects of Korean red ginseng on sexual arousal in menopausal women: placebo-controlled, double-blind crossover clinical study. J Sex Med 2010;7(4 Pt 1):1469-1477. PubMed
  37. Kim, T. H., Jeon, S. H., Hahn, E. J., Paek, K. Y., Park, J. K., Youn, N. Y., and Lee, H. L. Effects of tissue-cultured mountain ginseng (Panax ginseng CA Meyer) extract on male patients with erectile dysfunction. Asian J Androl 2009;11(3):356-361. PubMed
  38. Hu, Z., Yang, X., Ho, P. C., Chan, S. Y., Heng, P. W., Chan, E., Duan, W., Koh, H. L., and Zhou, S. Herb-drug interactions: a literature review. Drugs 2005;65(9):1239-1282. PubMed
  39. Zhang, R., Jie, J., Zhou, Y., Cao, Z., and Li, W. Long-term effects of Panax ginseng on disposition of fexofenadine in rats in vivo. Am J Chin Med 2009;37(4):657-667.
  40. Lee, Y. H., Lee, B. K., Choi, Y. J., Yoon, I. K., Chang, B. C., and Gwak, H. S. Interaction between warfarin and Korean red ginseng in patients with cardiac valve replacement. Int J Cardiol. 11-19-2010;145(2):275-276. PubMed
  41. Liu, P., Yin, H., Xu, Y., Zhang, Z., Chen, K., and Li, Y. Effects of ginsenoside Rg1 on postimplantation rat and mouse embryos cultured in vitro. Toxicol In Vitro 2006;20(2):234-238. PubMed
  42. Liu, P., Xu, Y., Yin, H., Wang, J., Chen, K., and Li, Y. Developmental toxicity research of ginsenoside Rb1 using a whole mouse embryo culture model. Birth Defects Res B Dev Reprod Toxicol 2005;74(2):207-209. PubMed
  43. Gurley, B. J., Gardner, S. F., Hubbard, M. A., Williams, D. K., Gentry, W. B., Cui, Y., and Ang, C. Y. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and DOI
  44. Wesnes KA, Faleni RA, Hefting NR, and et al. The cognitive, subjective, and physical effects of a Ginkgo biloba/Panax ginseng combination in healthy volunteers with neurasthenic complaints. Psychopharmacol Bull 1997;33(4):677-683.
  45. Martínez-Mir I, Rubio E, Morales-Olivas FJ, Palop-Larrea V. Transient ischemic attack secondary to hypertensive crisis related to Panax ginseng. Ann Pharmacother 2004;38(11):1970.
  46. Kakisaka Y, Ohara T, Tozawa H, Sato S, Katayama S, Suzuki T, Hino-Fukuyo N, Kure S. Panax ginseng: a newly identified cause of gynecomastia. Tohoku J Exp Med 2012;228(2):143-5. PubMed
  47. Malati CY, Robertson SM, Hunt JD, Chairez C, Alfaro RM, Kovacs JA, Penzak SR. Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants. J Clin Pharmacol 2012;52(6):932-9.
  48. Sen A. Orobuccolingual dyskinesia after long-term use of black cohosh and ginseng. J Neuropsychiatry Clin Neurosci 2013 Fall;25(4):E50. PubMed
  49. Oh MR, Park SH, Kim SY, Back HI, Kim MG, Jeon JY, Ha KC, Na WT, Cha YS, Park BH, Park TS, Chae SW. Postprandial glucose-lowering effects of fermented red ginseng in subjects with impaired fasting glucose or type 2 diabetes: a randomized, double-blind, pla
  50. Kim HG, Cho JH, Yoo SR, Lee JS, Han JM, Lee NH, Ahn YC, Son CG. Antifatigue effects of Panax ginseng C.A. Meyer: a randomised, double-blind, placebo-controlled trial. PLoS One 2013;8(4):e61271. PubMed
  51. Rhee MY, Kim YS, Bae JH, Nah DY, Kim YK, Lee MM, Kim HY. Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. J Altern Complement Med 2011;17(1):45-9.
  52. Bilgi N, Bell K, Ananthakrishnan AN, Atallah E. Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother 2010;44(5):926-8.
  53. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  54. Shah SA, Occiano A, Nguyen TA, et al. Electrocardiographic and blood pressure effects of energy drinks and panax ginseng in healthy volunteers: a randomized clinical trial. Int J Cardiol. 2016 Sep 1;218:318-23. PubMed
  55. Yang L, Li CL, Tsai TH. Preclinical Herb-Drug Pharmacokinetic Interaction of Panax ginseng Extract and Selegiline in Freely Moving Rats. ACS Omega. 2020;5(9):4682-4688.
  56. Shen L, Gwak SR, Joo JC, et al. Effectiveness and safety of Panax ginseng extract on hepatic dysfunction: A randomized, double-blind, placebo-controlled clinical trial. Evid Based Complement Alternat Med. 2020;2020:2689565.
  57. Kim Y, Jo JJ, Cho P, et al. Characterization of red ginseng-drug interaction by CYP3A activity increased in high dose administration in mice. Biopharm Drug Dispos. 2020;41(7):295-306. PubMed
  58. Bessell E, Fuller NR, Markovic TP, et al. Effects of a-cyclodextrin on cholesterol control and hydrolyzed ginseng extract on glycemic control in people with prediabetes: a randomized clinical trial. JAMA Netw Open 2020 Nov 2;3(11):e2023491.
  59. Lee SR, Hur K, Cho S. Subcorneal pustular dermatosis as a cause of pityriasis amiantacea in a young child. JAAD Case Rep 2021;18:40-44. PubMed
  60. Liu J, Chang D, Cordato D, et al. A pilot randomized controlled trial of WeiNaoKang (SaiLuoTong) in treating vascular dementia. Aging Med (Milton). 2022;5(4):246-256. PubMed
  61. Shin D, Yoon BI, Bang S, et al. Safety and Efficacy Assessment of Red Ginseng Oil (RXGIN) in Men with Lower Urinary Tract Symptoms in a Randomized, Double-Blind, Placebo-Controlled Trial. World J Mens Health 2023. PubMed
  62. Shin MB, Kim SA, Lee S, et al. Pharmacokinetic Comparison of Ginsenosides between Fermented and Non-Fermented Red Ginseng in Healthy Volunteers. Pharmaceutics 2022;14(12):2807. PubMed
  63. Gao J, Shi J, Ma X, et al. Effects of ginseng berry saponins from panax ginseng on glucose metabolism of patients with prediabetes: A randomized, double-blinded, placebo-controlled, crossover trial. Phytomedicine 2024;132:155842. PubMed
  64. Cho SK, Song YJ, Han JY, Kim HW, Nam E, Sung YK. Effectiveness of Korean Red Ginseng on fatigue in patients with rheumatic diseases: a randomized, double-blind, placebo-controlled study. Korean J Intern Med 2024;39(4):680-690. PubMed
  65. Arabi SM, Shahraki-Jazinaki M, Nayyerabadi M, et al. The Effect of Ginseng Supplementation on Lipid Profile: GRADE-assessed Systematic Review and Dose-response Meta-analysis of Randomized Controlled Trials. Curr Pharm Des 2024;30(26):2047-205. PubMed
  66. Zeng X, Zhou X, Zhang A, et al. Pityriasis Rosea-Like Eruption following anti-fatigue traditional herbs: Aconitum carmichaelii Debx and Panax Ginseng suspected. BMC Complement Med Ther 2024;24(1):248. PubMed

See these in context on the Panax Ginseng 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 →

Evodia 13 references
  1. Sheu JR, Kan YC, Hung WC, et al. The antiplatelet activity of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, is mediated through inhibition of phospholipase C. Thromb Res 1998;92:53-64. PubMed
  2. Sheu JR, Hung WC, Lee YM, Yen MH. Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa. Eur J Pharmacol 1996;318:469-75. PubMed
  3. Ueng YF, Tsai TH, Don MJ, et al. Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid of the medicinal herb Evodia rutaecarpa, in rats. J Pharm Pharmacol 2005;57:227-32.
  4. King CL, Kong YC, Wong NS, et al. Uterotonic effect of Evodia rutaecarpa alkaloids. J Nat Prod 1980;43:577-82. PubMed
  5. Ueng YF, Jan WC, Lin LC, et al. The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes. Drug Metab Dispos 2002;30:349-53. PubMed
  6. Iwata H, Tezuka Y, Kadota S, et al. Mechanism-based inactivation of human liver microsomal CYP3A4 by rutaecarpine and limonin from Evodia fruit extract. Drug Metab Pharmacokinet 2005;20:34-45. PubMed
  7. Sheu JR, Hung WC, Wu CH, et al. Antithrombotic effect of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, on platelet plug formation in in vivo experiments. Br J Haematol 2000;110:110-5.
  8. Tsai TH, Chang CH, Lin LC. Effects of Evodia rutaecarpa and rutaecarpine on the pharmacokinetics of caffeine in rats. Planta Med 2005;71:640-5.
  9. Lee SK, Kim NH, Lee J, et al. Induction of cytochrome P450s by rutaecarpine and metabolism of rutaecarpine by cytochrome P450s. Planta Med 2004;70:753-7. PubMed
  10. Baburin I, Varkvisser R, Schramm A, et al. Dehydroevodiamine and hortiamine, alkaloids from the traditional Chinese herbal drug Evodia rutaecarpa, are IKr blockers with proarrhythmic effects in vitro and in vivo. Pharmacol Res. 2018 May;131:150-163. DOI
  11. Zhang W, Guo J, Wang D, et al. Effect of CYP3A inducer/inhibitor on pharmacokinetics of five alkaloids in Evodiae Fructus. Chem Biol Interact 2020;327:109146. PubMed
  12. Huang CJ, Huang WC, Lin WT, et al. Rutaecarpine, an alkaloid from Evodia rutaecarpa, can prevent platelet activation in humans and reduce microvascular thrombosis in mice: crucial role of the PI3K/Akt/GSK3ß signal axis through a cyclic nucleotides/VASP-in
  13. Bista SR, Lee SK, Thapa D, et al. Effects of oral rutaecarpine on the pharmacokinetics of intravenous chlorzoxazone in rats. Toxicol Res 2008;24(3):195-9. PubMed

See these in context on the Evodia monograph →

Coenzyme Q10 40 references
  1. Kamikawa T, Kobayashi A, Yamashita T, et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol 1985;56:247-51. PubMed
  2. Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med 1994;S265-72. PubMed
  3. Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet 1994;334:1372-3. PubMed
  4. Singh RB, Niaz MA, Rastogi SS, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999;13:203-8. PubMed
  5. Portakal O, Ozkaya O, Erden Inal M, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-84. PubMed
  6. Lund EL, Quistorff B, Spang-Thomsen M, Kristjansen PE. Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol (Praha) 1998;43:505-6. PubMed
  7. Langsjoen PH, Langsjoen PH, Folkers K. Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy. Am J Cardiol 1990;65:521-3. PubMed
  8. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7. DOI
  9. Landbo C, Almdal TP. [Interaction between warfarin and coenzyme Q10]. Ugeskr Laeger 1998;160:3226-7.
  10. Baggio E, Gandini R, Plauncher AC, et al. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 1994;15 Suppl:S287-94. PubMed
  11. Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J 2001;94:1112-7. PubMed
  12. The Huntington Study Group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurology 2001;57:397-404.
  13. Hodgson JM, Watts GF, Playford DA, et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002;56:1137-42. PubMed
  14. Singh RB, Neki NS, Kartikey K, et al. Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. Mol Cell Biochem 2003;246:75-82. DOI
  15. Porterfield LM. Why did the response to warfarin change? RN 2000;63:107.
  16. Sandor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial. Neurology 2005;64:713-5. PubMed
  17. Engelsen J, Nielsen JD, Winther K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thromb Haemost 2002;87:1075-6. DOI
  18. Berman M, Erman A, Ben-Gal T, et al. Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study. Clin Cardiol 2004;27:295–9. PubMed
  19. Storch A, Jost WH, Vieregge P, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol 2007;64:938-44. DOI
  20. Digiesi V, Cantini F, Oradei A, et al. Coenzyme Q10 in essential hypertension. Mol Aspects Med 1994;15 Suppl:s257-63. PubMed
  21. Yamagami T, Takagi M, Akagami H, et al. Effect of coenzyme Q10 on essential hypertension, a double blind controlled study. In: Folkers KA, Yamamura Y, eds. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 5. Amsterdam: Elsevier Science Publications, 19
  22. Ho MJ, Bellusci A, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension (review). Cochrane Database Syst Rev 2009;(4):CD007435. PubMed
  23. Rosenfeldt, F. L., Haas, S. J., Krum, H., Hadj, A., Ng, K., Leong, J. Y., and Watts, G. F. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum.Hypertens. 2007;21(4):297-306. PubMed
  24. Stamelou, M., Reuss, A., Pilatus, U., Magerkurth, J., Niklowitz, P., Eggert, K. M., Krisp, A., Menke, T., Schade-Brittinger, C., Oertel, W. H., and Hoglinger, G. U. Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, place DOI
  25. Keogh A, Fenton S, Leslie C, et al. Randomised double-blind, placebo-controlled trial of coenzyme Q, therapy in class II and III systolic heart failure. Heart Lung Circ. 2003;12:135-41.
  26. Gane, E. J., Weilert, F., Orr, D. W., Keogh, G. F., Gibson, M., Lockhart, M. M., Frampton, C. M., Taylor, K. M., Smith, R. A., and Murphy, M. P. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C
  27. Lynch, D. R., Perlman, S. L., and Meier, T. A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia. Arch Neurol. 2010;67(8):941-947. PubMed
  28. Young, J. M., Florkowski, C. M., Molyneux, S. L., McEwan, R. G., Frampton, C. M., Nicholls, M. G., Scott, R. S., and George, P. M. A randomized, double-blind, placebo-controlled crossover study of coenzyme Q10 therapy in hypertensive patients with the me
  29. Ishiyama, T., Morita, Y., Toyama, S., Yamagami, T., and Tsukamoto, N. A clinical study of the effect of coenzyme Q on congestive heart failure. Jpn.Heart J 1976;17(1):32-42. PubMed
  30. Matthews, P. M., Ford, B., Dandurand, R. J., Eidelman, D. H., O'Connor, D., Sherwin, A., Karpati, G., Andermann, F., and Arnold, D. L. Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease. Neurology 1993;43(5
  31. Malm, C., Svensson, M., Sjoberg, B., Ekblom, B., and Sjodin, B. Supplementation with ubiquinone-10 causes cellular damage during intense exercise. Acta Physiol Scand. 1996;157(4):511-512. PubMed
  32. Singh, R. B., Wander, G. S., Rastogi, A., Shukla, P. K., Mittal, A., Sharma, J. P., Mehrotra, S. K., Kapoor, R., and Chopra, R. K. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc. PubMed
  33. Digiesi V, Cantini F, and Brodbeck B. Effect of coenzyme Q10 on essential arterial hypertension. Current Therapeutic Research 1990;47(5):841-845.
  34. Parkinson Study Group QE3 Investigators, Beal MF, Oakes D, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014;71(5):543-52.
  35. Alehagen U, Johansson P, Bjornstedt M, et al. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citi
  36. Ho MJ, Li EC, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane Database Syst Rev. 2016 Mar 3;3:CD007435. doi: 10.1002/14651858.CD007435.pub3. PubMed
  37. Tabrizi R, Akbari M, Sharifi N, Lankarani KB, Moosazadeh M, Kolahdooz F, et al. The effects of coenzyme Q10 supplementation on blood pressures among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials. PubMed
  38. Tsai IC, Hsu CW, Chang CH, Tseng PT, Chang KV. Effectiveness of coenzyme Q10 supplementation for reducing fatigue: A systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 2022;13:883251. PubMed
  39. Yaghini O, Hoseini N, Ghazavi MR, et al. A comparative study on the efficacy of coenzyme Q10 and amitriptyline in the prophylactic treatment of migraine headaches in children: A randomized controlled trial. Adv Biomed Res 2022;11:43. PubMed
  40. Hansen KS, Mogensen TH, Agergaard J, et al. High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: A randomized, phase 2, crossover trial. Lancet Reg Health Eur 2022. PubMed

See these in context on the Coenzyme Q10 monograph →

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

See these in context on the Grape monograph →

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