Major interaction on record — check this product against your medications before combining. Based on 8 of 11 ingredients. Check your meds →
Dietary supplement

Vexxum Ingredients & Drug Interactions

by PS ProSupps

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

First and foremost: checking Vexxum 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

Vexxum is a dietary supplement by PS ProSupps with 11 active ingredients. Its ingredients are commonly taken for mental alertness and reducing fatigue, improving athletic performance, headache and migraine relief.Based on those ingredients, 1,341 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Yohimbe bark extract, CocoaPro(TM), Caffeine Anhydrous. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Vexxum by PS ProSupps

Ask about any prescription or over-the-counter medication and we check it for interactions with Vexxum by PS ProSupps — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Vexxum by PS ProSupps

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 11 active ingredients.
  • “Vexxum Blend” is a proprietary blend — the label gives one combined amount (627 mg) without saying how much of each component you get.

Vexxum contains 11 active ingredients — three sources of caffeine (Caffeine Anhydrous, Caffeine Citrate, and Infinergy, a delayed-release caffeine product), plus Octopamine HCl, Yohimbe bark extract, Theacrine, Hordenine HCl, Sulbutiamine (a form of vitamin B1), Lotus seed extract, Rauwolfia vomitoria root extract, and CocoaPro (cocoa). These are meant to deliver a stimulant and energy boost.

The product also contains inactive ingredients: gelatin capsule material, maltodextrin, silica, magnesium stearate, titanium dioxide, and several food colorants (FD&C dyes).

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: Energy, focus, and athletic performance.
  • We looked for evidence on: Athletic performance, Chronic fatigue syndrome (CFS), Cognitive function, Fatigue, Memory, Mental alertness — and 4 related terms.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Caffeine is rated "Likely Effective" for Mental alertness.
  • Also on file: Caffeine is rated "Possibly Effective" for Memory.

For caffeine (present in three forms here), the evidence shows it is Effective for neonatal apnea and postoperative headache, and Likely Effective for mental alertness and athletic performance. For the other active ingredients — Octopamine, Yohimbe, Theacrine, Hordenine, Sulbutiamine, Lotus, Rauwolfia, and Cocoa — the data we hold shows Insufficient Reliable Evidence to rate their effectiveness for any use.

The evidence, ingredient by ingredient Caffeine Octopamine Yohimbe Theacrine Hordenine Sulbutiamine Lotus Cocoa

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 7 of the 8 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 5 of 8.
  • General safety write-ups exist for 8 of 8.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Caffeine in moderate doses is generally well tolerated in healthy adults, though high doses carry risks of serious side effects and can raise blood pressure. The three caffeine sources in this product mean total caffeine intake may be high.

Common side effects include anxiety, insomnia, tremor, nausea, headache, and restlessness; rarely, stroke has been reported. Small amounts of caffeine pass into breast milk, and high intake in pregnancy is linked to risks — ask your doctor about safe limits.

Yohimbe is a particular concern: it can cause serious heart and blood pressure effects (hypertension, fast heartbeat, chest discomfort, and in rare cases hypertensive crisis), and the active compound concentration varies unpredictably between supplements. The data advises against using Yohimbe during pregnancy and breastfeeding.

Octopamine is chemically similar to synephrine (a stimulant with severe cardiac potential); Health Canada caps its dose at 50 mg daily, yet clinical safety data is limited — one case report linked chronic use of an octopamine supplement to blood clots and heart attack. Hordenine, Theacrine, and Lotus extract have limited human safety data.

Sulbutiamine was used safely for up to 4 weeks in small trials but long-term safety is unknown. Cocoa is generally well tolerated in food amounts but this product contains cocoa as a supplement, and cocoa contains caffeine that adds to your total intake.

Side effects, ingredient by ingredient Caffeine Octopamine Yohimbe Theacrine Hordenine Sulbutiamine Lotus Cocoa

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?
  • 7 of the 8 matched ingredients can interact with medications — Lotus, Yohimbe, Cocoa, Caffeine, Theacrine, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications; lithium.
  • For scale: 1,342 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 Vexxum, check with your pharmacist or doctor if you take any of these: MAOIs (antidepressants like phenelzine or tranylcypromine) — Major severity risk; ephedrine or other stimulants — Major severity risk; blood pressure medications (antihypertensives); seizure medications (phenobarbital, carbamazepine); antipsychotics (clozapine) or other psychiatric drugs; sedatives or sleeping pills; heart medications (dipyridamole); or antibiotics called quinolones. Additionally, certain drugs used to treat acid reflux, diabetes, or blood clotting carry documented interactions.

Use the medication checker on this page to verify your specific prescriptions.

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.

Vexxum is a high-stimulant product designed for energy and athletic performance. If you take any prescription medications — especially blood pressure drugs, antidepressants, seizure medications, sedatives, heart medications, or antibiotics — you must check each one against the interaction tool before using this product.

Do not use if you take MAOIs or ephedrine. Because it contains multiple caffeine sources, total intake will be substantial; people sensitive to caffeine, those with heart or blood pressure concerns, or those pregnant or breastfeeding should talk to their pharmacist or doctor first.

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

Assessment coverage: 10 of 11 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jul 24, 2015.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Vexxum, straight from the product label.

Brand PS ProSupps
Barcode (UPC) 682055406800
Net contents 45 Capsule(s)
Market status On market
Date entered into DSLD Jul 24, 2015
DSLD ID 47699
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Vexxum by PS ProSupps, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Capsule(s)
Maximum serving Sizes:
1 Capsule(s)
Servings per container
45
UPC/BARCODE
682055406800
IngredientAmount% DV
Caffeine Anhydrous0 NP--
Octopamine HCl0 NP--
Yohimbe bark extract0 NP--
Theacrine0 NP--
Caffeine Citrate0 NP--
Hordenine HCl0 NP--
Sulbutiamine0 NP--
Lotus seed extract0 NP--
Rauwolfia vomitoria root extract0 NP--
Infinergy0 NP--
Vexxum Blend627 mg--
CocoaPro(TM)0 NP--

Other ingredients: Gelatin, Maltodextrin, Silica, Magnesium Stearate, Titanium Dioxide, FD&C Red #40, FD&C Green #3, FD&C Red #3, FD&C Yellow #6, FD&C Blue #1

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.
Precautions

Caffeine Warning: The recommended serving of this product contains approximately 320mgs of caffeine which is as much caffeine as 4 cups of coffee. Do not consume caffeine or synephrine from other sources, including but not limited to coffee, tea, soda and other dietary supplements or medications containing phenylephrine, ephedrine, pseudoephedrine, caffeine or other stimulants. Too much caffeine may cause nervousness, irritability, sleeplessness, and occasionally rapid heartbeat. Discontinue use if you experience dizziness, severe headache, rapid heartbeat or shortness of breath.

WARNING: NOT FOR USE BY INDIVIDUALS UNDER THE AGE OF 18 YEARS.

DO NOT USE IF PREGNANT OR NURSING.

KEEP OUT OF REACH OF CHILDREN.

DO NOT CONSUME THIS PRODUCT IF YOU HAVE A MEDICAL CONDITION AND/OR TAKING ANY PRESCRIPTION MEDICATION.

DO NOT EXCEED RECOMMENDED SERVINGS. DO NOT USE THIS PRODUCT IF YOU ARE AT RISK OR ARE BEING TREATED FOR HIGH BLOOD PRESSURE, KIDNEY, THYROID OR PSYCHIATRIC DISEASE, ANXIETY, DEPRESSION, SEIZURE, ENLARGED PROSTATE OR STROKE. BEFORE BEGINNING ANY SUPPLEMENT OR TRAINING PROGRAM ALWAYS CONSULT A PHYSICIAN FIRST.

DO NOT EXCEED 4 CAPSULES PER DAY. CONSULT WITH YOUR PHYSICIAN PRIOR TO USING THIS PRODUCT.

Seals/Symbols

MADE IN USA

US

prosupps(R) RESULTS...PERIOD!+

Ps(R)

TEACRINE(R)

GLUTEN FREE

Formula

Caffeine Warning: The recommended serving of this product contains approximately 320mgs of caffeine which is as much caffeine as 4 cups of coffee.

FDA Disclaimer Statement

+ THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS PRODUCT IS NOT INTENDED TO DIAGNOSE, TREAT, CURE OR PREVENT ANY DISEASE.

General Statements

>>>THERMOGENIC METABOLIZER+

> Appetite Craving Suppression Control+ > Weight-Loss Amplifier+

Suggested/Recommended/Usage/Directions

> One Cap Daily Dose+

SUGGESTED USE: AS A DIETARY SUPPLEMENT, TAKE 1 CAPSULE PER SERVING.

FDA Statement of Identity

DIETARY SUPPLEMENT

Brand IP Statement(s)

"TeaCrine(R) is a registered trademark and protected by patents Pending, Serial No. 61/903,362; under exclusive global distribution by Compound Solutions, Inc."

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

See for yourself

Vexxum by PS ProSupps label

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

Vexxum 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 Vexxum by PS ProSupps

These are the 11 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Capsule(s) Dosage formCapsule Servings per container45 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Vexxum Blend

627 mg per serving

Other (inactive) ingredients: Gelatin, Maltodextrin, Silica, Magnesium Stearate, Titanium Dioxide, FD&C Red #40, FD&C Green #3, FD&C Red #3, FD&C Yellow #6, FD&C Blue #1. These complete the product’s ingredient list but are not active constituents.

Interaction report

Vexxum by PS ProSupps Drug Interactions

Want to check YOUR meds against Vexxum?

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
1,341Drugs
17 Major 1,058 Moderate 266 Minor

Ingredients driving the most interactions

Yohimbe bark extract 1,125
CocoaPro(TM) 661
Caffeine Anhydrous 655
Octopamine HCl 352
Hordenine HCl 329

Individual Drug Interactions

The ingredients in Vexxum interact with 1,341 drugs. Click any drug to see the details.

7 of the 11 ingredients in Vexxum interact with drugs. Each result below shows which ingredient is responsible. Yohimbe bark extract CocoaPro(TM) Caffeine Anhydrous Octopamine HCl Hordenine HCl Theacrine Lotus seed extract

Each ingredient & the kinds of drugs it affects

For each ingredient in Vexxum 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.

Yohimbe bark extract13 drug types · 1,125 drugs

Monoamine Oxidase Inhibitors (Maois)

Concomitant use of MAOIs with yohimbe can result in additive effects.
Yohimbine, a constituent of yohimbe, has MAO inhibitory effects. At high doses, yohimbine is a non-selective inhibitor of MAO.

Likelihood Likely Evidence D
Antihypertensive Drugs

Theoretically, yohimbe might reduce the effects of antihypertensive drugs.
Yohimbine, a constituent of yohimbe, is an alpha-2 adrenoceptor antagonist and has been reported to increase blood pressure in clinical research. Theoretically, concomitant use of yohimbe and antihypertensive drugs can interfere with blood pressure control.

Likelihood Probable Evidence D
Clonidine (Catapres)

Theoretically, yohimbe might precipitate clonidine withdrawal.
Chronic clonidine use can downregulate alpha-2 adrenoreceptors. Animal research and one human case report suggest that concomitant administration of yohimbine, an alpha-2 adrenoceptor antagonist, may precipitate clonidine withdrawal and lead to sympathomimetic toxicity, including hypertensive crisis.

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

CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP2D6 isoenzymes. Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine and reduces the clearance of yohimbine compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers..

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

Theoretically, yohimbe might increase the levels and adverse effects of CYP2D6 substrates.
In vitro research suggests that yohimbine, a constituent of yohimbe bark, inhibits CYP2D6 enzyme activity.

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

Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of yohimbine, a constituent of yohimbe bark.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP3A4 enzymes. Theoretically, drugs that inhibit CYP3A4 might increase the levels and adverse effects of yohimbine.

Likelihood Possible Evidence D
Paroxetine (Paxil)

Paroxetine decreases the clearance of yohimbine and may increase its effects.
Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine by about 350% and reduces the clearance of yohimbine by about 80% compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers. No significant changes in pharmacokinetic parameters of yohimbine were observed with coadministration of paroxetine in patients who are poor CYP2D6 metabolizers.

Likelihood Probable Evidence B
Phenothiazines

Theoretically, using yohimbine with phenothiazines might have additive effects.
Yohimbine, a constituent of yohimbe, has alpha-2 adrenergic antagonist effects. Theoretically, combining it with phenothiazines can cause additive alpha-2 adrenergic antagonism.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, taking yohimbe with stimulant drugs can have additive effects.
Yohimbine, a constituent of yohimbe, has sympathomimetic effects and increases blood pressure in a dose-dependent manner. Theoretically, taking yohimbe with stimulant drugs can have additive stimulant and hypertensive effects.

Likelihood Possible Evidence D
Tricyclic Antidepressants (Tcas)

Theoretically, taking yohimbe with TCAs can increase adverse effects.
A small clinical study in patients taking TCAs for at least 4 weeks shows that receiving doses of intravenous yohimbine 2.5-20 mg daily for up to 7 days precipitates severe anxiety, agitation, and tremor. The effects of yohimbe bark itself are unclear; oral yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, combining yohimbe bark with antiplatelet or anticoagulant drugs might have additive effects; however, this has not been reported in clinical research.
Research in healthy adults shows that taking yohimbine, a constituent of yohimbe bark, in doses of 8 mg or more, seems to inhibit platelet aggregation in vitro by binding to the alpha-2 adrenoceptor. The effects of yohimbe bark itself are unclear; yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed.

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

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

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

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

Likelihood Possible Evidence D
Yohimbe bark extract full monograph & interactions

CocoaPro(TM)37 drug types · 661 drugs

Ace Inhibitors (Aceis)

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

Likelihood Possible Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Alcohol (Ethanol)

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Antihypertensive Drugs

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

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

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

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

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

Likelihood Possible Evidence D
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Ephedrine

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Flutamide (Eulexin)

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

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

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

Likelihood Possible Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenylpropanolamine

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

Likelihood Probable Evidence B
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Stimulant Drugs

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

Likelihood Probable Evidence C
Theophylline

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

Likelihood Probable Evidence B
CocoaPro(TM) full monograph & all 37 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

Octopamine HCl3 drug types · 352 drugs

Antihypertensive Drugs

In humans, octopamine 450-600 mg daily increases blood pressure in hypotensive patients. However, evidence from animal research suggests that octopamine can lower blood pressure. Theoretically, concomitant use of octopamine and antihypertensive drugs might potentiate and/or reduce the activity of antihypertensive drugs.
Some antihypertensive drugs include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.

Likelihood Possible Evidence B
Monoamine Oxidase Inhibitors (Maois)

Octopamine is metabolized by monoamine oxidase. Theoretically, concurrent use of MAOIs with octopamine might increase the effects and side effects of octopamine. Tell patients taking MAOIs to avoid using octopamine. Some MAOIs include phenelzine (Nardil), tranylcypromine (Parnate), and others.

Likelihood Possible Evidence D
Stimulant Drugs

Octopamine is thought to have stimulant effects. Theoretically, taking octopamine with other stimulant drugs might increase the risk of hypertension and adverse cardiovascular effects.
Some stimulant drugs include amphetamine, caffeine, diethylpropion (Tenuate), methylphenidate, phentermine (Ionamin), pseudoephedrine (Sudafed, others), and many others.

Likelihood Possible Evidence D
Octopamine HCl full monograph & interactions

Hordenine HCl3 drug types · 329 drugs

Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Stimulant Drugs

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

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

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

Likelihood Possible Evidence D
Hordenine HCl full monograph & interactions

Theacrine1 drug type · 248 drugs

Cns Depressants

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

Likelihood Possible Evidence D
Theacrine full monograph & interactions

Lotus seed extract3 drug types · 212 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, concurrent use of lotus with other antiplatelet drugs might reduce platelet aggregation and increase the risk of bleeding.
Neferine and isoliensinine, constituents of lotus, have been shown to inhibit platelet aggregation, in vitro. These constituents can inhibit the production of pro-aggregating factors like prostaglandins.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, lotus might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia.
Animal research shows that the ethanolic extract of lotus reduces blood glucose levels and potentiates the effects of injected insulin. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Likelihood Possible Evidence D
Pentobarbital (Nembutal)

Theoretically, taking lotus concomitantly with pentobarbital might increase sedation.
Animal research shows that lotus extract increases pentobarbitone-induced sleeping time. It is not known if this occurs in humans or if this effect occurs with other barbiturates or sedatives.

Likelihood Possible Evidence D
Lotus seed extract full monograph & interactions
The maker

Brand information

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

PS ProSupps

See all PS ProSupps products
Name
PROSUPPS USA, LLC.
Street Address
601 Century Pkwy. Ste. 300
City
Allen
State
TX
ZipCode
75013
Web Address
www.prosupps.com
Pharmacist Counseling Corner

Vexxum by PS ProSupps: Common Questions

Does Vexxum by PS ProSupps interact with any medications?
Yes. Based on its ingredients, Vexxum has a known interaction with 1,341 medications, including 17 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Vexxum contains 11 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 Vexxum have a lot of caffeine?
Yes. This product contains three separate caffeine sources: Caffeine Anhydrous, Caffeine Citrate, and Infinergy (a delayed-release caffeine). This means your total caffeine intake from this single product will be substantial. If you also drink coffee, tea, or take other supplements with caffeine, your combined intake could be very high.
Can I take Vexxum if I'm pregnant or breastfeeding?
The data advises against Yohimbe during pregnancy — it may affect the uterus and is considered unsafe. Caffeine in high amounts is linked to pregnancy risks; the facts recommend asking your doctor about safe limits. For breastfeeding, small amounts of caffeine from Vexxum pass into breast milk and can affect the baby, and there isn't enough safety data on several other ingredients. Talk to your doctor or pharmacist about whether this product is right for you.
What are the most common side effects I might feel?
From the caffeine, expect possible anxiety, insomnia, jitteriness, tremors, nausea, headache, and restlessness. Yohimbe can cause anxiety, agitation, diarrhea, flushing, increased urination, fast heartbeat, tremor, dizziness, and nausea — and at higher doses, dangerous spikes in blood pressure. Because this is a multi-ingredient stimulant product, the overall effect on your heart rate and blood pressure could be significant.
What makes Vexxum different from just drinking coffee?
Vexxum packs multiple stimulants — three caffeine forms, plus Yohimbe, Octopamine, Hordenine, and Theacrine — into one capsule. These ingredients have different chemical pathways and some interact with medications in ways pure caffeine does not. The combination is much more potent and complex than coffee alone.
Is it safe to use Vexxum with my antidepressant?
It depends on your antidepressant. If you take an MAOI (an older class like phenelzine or tranylcypromine), do not use Vexxum — Yohimbe and Octopamine can cause a dangerous rise in blood pressure. For other antidepressants, check with your pharmacist using the medication tool on this page, because some have documented interactions with the caffeine or Yohimbe in this product.
Why do I need to stop this supplement before a stress test?
Vexxum contains caffeine, which blocks the effects of dipyridamole (a medication doctors use during heart stress tests to dilate blood vessels). If you take this product, caffeine should be stopped 24 hours before the test so dipyridamole can work properly.

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

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Vexxum label
Go deeper

The Full Monographs Behind Vexxum’s Ingredients

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

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

Octopamine

Interacts with 352 drugs

Octopamine is a stimulant-like compound found in small amounts in some plants (such as bitter orange) and made naturally in the body. It is marketed mostly in weight-loss and sports suppleme...

Read the full Octopamine monograph → Herb & supplement monograph

Yohimbe

Interacts with 1,125 drugs

Yohimbe is a West African tree bark that contains yohimbine, a compound mainly promoted for erectile dysfunction and as an aphrodisiac. A prescription form of yohimbine has some evidence for...

Read the full Yohimbe monograph → Herb & supplement monograph

Theacrine

Interacts with 248 drugs

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

Read the full Theacrine monograph → Herb & supplement monograph

Hordenine

Interacts with 329 drugs

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

Read the full Hordenine monograph → Herb & supplement monograph

Sulbutiamine

Sulbutiamine is a man-made, fat-soluble form of vitamin B1 (thiamine) developed in Japan, often taken for fatigue and to support mental energy and focus. Human evidence is limited and mostly...

Read the full Sulbutiamine monograph → Herb & supplement monograph

Lotus

Interacts with 212 drugs

Lotus is an edible aquatic plant used in food and traditional medicine across Asia, with parts like the seeds, leaves, and flowers taken for digestion, calm, and overall wellness. Most healt...

Read the full Lotus monograph → Herb & supplement monograph

Cocoa

Interacts with 661 drugs

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

Read the full Cocoa monograph →
Sources

Sources & How We Checked

Vexxum'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 440 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.

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

See these in context on the Caffeine monograph →

Octopamine 6 references
  1. Visentin V, Morin N, Fontana E, et al. Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases. J Pharmacol Exp Ther 2001;299:96-104.
  2. Health Canada. Synephrine, Octopamine and Caffeine Health Risk Assessment (HRA) Report. Approved May 16, 2011. Accessed November 6, 2019. Available at: http://www.nutratechinc.com/advz/Studies2011/Safety/S1%20Health%20Canada%200511.pdf.
  3. Pawar RS, Grundel E. Overview of regulation of dietary supplements in the USA and issues of adulteration with phenethylamines (PEAs). Drug Test Anal 2017;9:500-517. PubMed
  4. Beaumont RE, Cordery P, James LJ, Watson P. Supplementation with a low-dose of octopamine does not influence endurance cycling performance in recreationally active men. J Sci Med Sport. 2017;20(10):952-956. PubMed
  5. Smedema JP, Müller GJ. Coronary spasm and thrombosis in a bodybuilder using a nutritional supplement containing synephrine, octopamine, tyramine and caffeine. S Afr Med J. 2008;98(5):372-3.
  6. Fontana E, Morin N, Prévot D, Carpéné C. Effects of octopamine on lipolysis, glucose transport and amine oxidation in mammalian fat cells. Comp Biochem Physiol C Toxicol Pharmacol. 2000;125(1):33-44. PubMed

See these in context on the Octopamine monograph →

Yohimbe 66 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. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  4. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  5. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980;60:85-7.
  6. Teloken C, Rhoden EL, Sogari P, et al. Therapeutic effects of high dose yohimbine hydrochloride on organic erectile dysfunction. J Urol 1998;159:122-4. PubMed
  7. Jacobsen FM. Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 1992;53:119-22.
  8. Hollander E, McCarley A. Yohimbine treatment of sexual side effects induced by serotonin reuptake blockers. J Clin Psychiatry 1992;53:207-9.
  9. Sandler B, Aronson P. Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome. Urol 1993;41:343-5. PubMed
  10. Kearney T, Tu N, Haller C. Adverse drug events associated with yohimbine-containing products: a retrospective review of the California Poison Control System reported cases. Ann Pharmacother 2010;44:1022-9. PubMed
  11. VandenBrink, B. M., Foti, R. S., Rock, D. A., Wienkers, L. C., and Wahlstrom, J. L. Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate-dependent inhibition. Drug Metab Dispos. 2012;40(1):47-53. PubMed
  12. Abebe, W. An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations. J Dent.Hyg. 2003;77(1):37-46.
  13. Mustonen, P., Savola, J., and Lassila, R. Atipamezole, an imidazoline-type alpha(2)-adrenoceptor inhibitor, binds to human platelets and inhibits their adrenaline-induced aggregation more effectively than yohimbine. Thromb.Res 8-1-2000;99(3):231-237.
  14. Cameron, O. G., Zubieta, J. K., Grunhaus, L., and Minoshima, S. Effects of yohimbine on cerebral blood flow, symptoms, and physiological functions in humans. Psychosom.Med 2000;62(4):549-559. PubMed
  15. Bowes, M. P., Peters, R. H., Kernan, W. J., Jr., and Hopper, D. L. Effects of yohimbine and idazoxan on motor behaviors in male rats. Pharmacol.Biochem.Behav. 1992;41(4):707-713.
  16. Bagheri, H., Schmitt, L., Berlan, M., and Montastruc, J. L. Effect of 3 weeks treatment with yohimbine on salivary secretion in healthy volunteers and in depressed patients treated with tricyclic antidepressants. Br J Clin Pharmacol 1992;34(6):555-558. PubMed
  17. Bagheri, H., Bompart, G., Girolami, J. P., Montastruc, J. L., and Montastruc, P. Is yohimbine-induced increase in salivary secretion a kinin-dependent mechanism? Fundam.Clin Pharmacol 1992;6(1):17-20. PubMed
  18. Swann, A. C., Birnbaum, D., Jagar, A. A., Dougherty, D. M., and Moeller, F. G. Acute yohimbine increases laboratory-measured impulsivity in normal subjects. Biol.Psychiatry 5-15-2005;57(10):1209-1211. PubMed
  19. Adeniyi, A. A., Brindley, G. S., Pryor, J. P., and Ralph, D. J. Yohimbine in the treatment of orgasmic dysfunction. Asian J Androl 2007;9(3):403-407. PubMed
  20. Murburg, M. M., Villacres, E. C., Ko, G. N., and Veith, R. C. Effects of yohimbine on human sympathetic nervous system function. J Clin Endocrinol.Metab 1991;73(4):861-865. PubMed
  21. Giampreti, A., Lonati, D., Locatelli, C., Rocchi, L., and Campailla, M. T. Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol.(Phila) 2009;47(8):827-829. PubMed
  22. Bloomer, R. J., Canale, R. E., Blankenship, M. M., Hammond, K. G., Fisher-Wellman, K. H., and Schilling, B. K. Effect of the dietary supplement Meltdown on catecholamine secretion, markers of lipolysis, and metabolic rate in men and women: a randomized,
  23. Myers, A. and Barrueto, F., Jr. Refractory priapism associated with ingestion of yohimbe extract. J Med Toxicol. 2009;5(4):223-225.
  24. Berlin, I., Crespo-Laumonnier, B., Cournot, A., Landault, C., Aubin, F., Legrand, J. C., and Puech, A. J. The alpha 2-adrenergic receptor antagonist yohimbine inhibits epinephrine-induced platelet aggregation in healthy subjects. Clin Pharmacol.Ther. 199
  25. Swann, A. C. Mechanisms of impulsivity in bipolar disorder and related illness. Epidemiol.Psichiatr.Soc. 2010;19(2):120-130.
  26. Shibao, C., Okamoto, L. E., Gamboa, A., Yu, C., Diedrich, A., Raj, S. R., Robertson, D., and Biaggioni, I. Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension 2010;56(5) PubMed
  27. Soeter, M. and Kindt, M. Stimulation of the noradrenergic system during memory formation impairs extinction learning but not the disruption of reconsolidation. Neuropsychopharmacology 2012;37(5):1204-1215. PubMed
  28. Cimolai, N. and Cimolai, T. Yohimbine use for physical enhancement and its potential toxicity. J Diet.Suppl 2011;8(4):346-354. PubMed
  29. Bagheri, H., Berlan, M., Montastruc, J. L., and Montastruc, P. Yohimbine and lacrimal secretion. Br J Clin Pharmacol. 1990;30(1):151-152.
  30. Landis, E. and Shore, E. Yohimbine-induced bronchospasm. Chest 1989;96(6):1424. PubMed
  31. Susset, J. G., Tessier, C. D., Wincze, J., Bansal, S., Malhotra, C., and Schwacha, M. G. Effect of yohimbine hydrochloride on erectile impotence: a double-blind study. J Urol. 1989;141(6):1360-1363. PubMed
  32. Chatelut, E., Rispail, Y., Berlan, M., and Montastruc, J. L. Yohimbine increases human salivary secretion. Br.J Clin Pharmacol. 1989;28(3):366-368. PubMed
  33. Montastruc, P., Berlan, M., and Montastruc, J. L. Effects of yohimbine on submaxillary salivation in dogs. Br J Pharmacol 1989;98(1):101-104. PubMed
  34. Charney, D. S., Price, L. H., and Heninger, G. R. Desipramine-yohimbine combination treatment of refractory depression. Implications for the beta-adrenergic receptor hypothesis of antidepressant action. Arch.Gen.Psychiatry 1986;43(12):1155-1161. PubMed
  35. Braddock, L., Cowen, P. J., Elliott, J. M., Fraser, S., and Stump, K. Binding of yohimbine and imipramine to platelets in depressive illness. Psychol.Med 1986;16(4):765-773. PubMed
  36. Bolme, P., Corrodi, H., Fuxe, K., Hokfelt, T., Lidbrink, P., and Goldstein, M. Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. Eur J Pharm PubMed
  37. Charney, D. S., Heninger, G. R., and Sternberg, D. E. Assessment of alpha 2 adrenergic autoreceptor function in humans: effects of oral yohimbine. Life Sci 6-7-1982;30(23):2033-2041.
  38. Boon, N. A., Elliott, J. M., Grahame-Smith, D. G., John-Green, T., and Stump, K. A comparison of alpha 2-adrenoreceptor binding characteristics of intact human platelets identified by [3H]-yohimbine and [3H]- dihydroergocryptine. J Auton.Pharmacol 1983;3
  39. Andrejak, M., Ward, M., and Schmitt, H. Cardiovascular effects of yohimbine in anaesthetized dogs. Eur.J Pharmacol 10-28-1983;94(3-4):219-228. PubMed
  40. Brodde, O. E., Anlauf, M., Arroyo, J., Wagner, R., Weber, F., and Buck, K. D. Hypersensitivity of adrenergic receptors and blood-pressure response to oral yohimbine in orthostatic hypotension. N.Engl.J Med 4-28-1983;308(17):1033-1034. PubMed
  41. Charney, D. S., Heninger, G. R., and Redmond, D. E., Jr. Yohimbine induced anxiety and increased noradrenergic function in humans: effects of diazepam and clonidine. Life Sci. 7-4-1983;33(1):19-29. PubMed
  42. Knoll, L. D., Benson, R. C., Jr., Bilhartz, D. L., Minich, P. J., and Furlow, W. L. A randomized crossover study using yohimbine and isoxsuprine versus pentoxifylline in the management of vasculogenic impotence. J Urol. 1996;155(1):144-146. DOI
  43. Betz, J. M., White, K. D., and der Marderosian, A. H. Gas chromatographic determination of yohimbine in commercial yohimbe products. J AOAC Int 1995;78(5):1189-1194. DOI
  44. Bagheri, H., Chale, J. J., Guyen, L. N., Tran, M. A., Berlan, M., and Montastruc, J. L. Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist. Fundam.Clin Pharmacol 1995;9(3):248-254.
  45. Kennedy, S. H., Gnam, W., Ralevski, E., and Brown, G. M. Melatonin responses to clonidine and yohimbine challenges. J Psychiatry Neurosci. 1995;20(4):297-304.
  46. Musso, N. R., Vergassola, C., Pende, A., and Lotti, G. Yohimbine effects on blood pressure and plasma catecholamines in human hypertension. Am J Hypertens. 1995;8(6):565-571. PubMed
  47. Morgan, C. A., III, Southwick, S. M., Grillon, C., Davis, M., Krystal, J. H., and Charney, D. S. Yohimbine-facilitated acoustic startle reflex in humans. Psychopharmacology (Berl) 1993;110(3):342-346. PubMed
  48. Adler, L. E., Hoffer, L., Nagamoto, H. T., Waldo, M. C., Kisley, M. A., and Giffith, J. M. Yohimbine impairs P50 auditory sensory gating in normal subjects. Neuropsychopharmacology 1994;10(4):249-257. PubMed
  49. Biaggioni, I., Robertson, R. M., and Robertson, D. Manipulation of norepinephrine metabolism with yohimbine in the treatment of autonomic failure. J Clin Pharmacol. 1994;34(5):418-423. PubMed
  50. Kenney, W. L., Zappe, D. H., Tankersley, C. G., and Derr, J. A. Effect of systemic yohimbine on the control of skin blood flow during local heating and dynamic exercise. Am J Physiol 1994;266(2 Pt 2):H371-H376. PubMed
  51. Friesen, K., Palatnick, W., and Tenenbein, M. Benign course after massive ingestion of yohimbine. J Emerg.Med 1993;11(3):287-288. PubMed
  52. Bierer, L. M., Aisen, P. S., Davidson, M., Ryan, T. M., Stern, R. G., Schmeidler, J., and Davis, K. L. A pilot study of oral physostigmine plus yohimbine in patients with Alzheimer disease. Alzheimer Dis.Assoc.Disord. 1993;7(2):98-104. PubMed
  53. Mann, K., Klingler, T., Noe, S., Roschke, J., Muller, S., and Benkert, O. Effects of yohimbine on sexual experiences and nocturnal penile tumescence and rigidity in erectile dysfunction. Arch.Sex Behav. 1996;25(1):1-16. PubMed
  54. Rowland, D. L., Kallan, K., and Slob, A. K. Yohimbine, erectile capacity, and sexual response in men. Arch Sex Behav 1997;26(1):49-62.
  55. Bremner, J. D., Innis, R. B., Ng, C. K., Staib, L. H., Salomon, R. M., Bronen, R. A., Duncan, J., Southwick, S. M., Krystal, J. H., Rich, D., Zubal, G., Dey, H., Soufer, R., and Charney, D. S. Positron emission tomography measurement of cerebral metaboli
  56. Riley AJ, Goodman R, Kellett JM, and et al. Double blind trial of yohimbine hydrochloride in the treatment of erection inadequacy. Sexual Marital Ther 1989;4(1):17-26. DOI
  57. Cohen PA, Wang YH, Maller G, DeSouza R, Khan IA. Pharmaceutical quantities of yohimbine found in dietary supplements in the USA. Drug Test Anal. 2015 Sep 22. PubMed
  58. Ruck B, Shih RD, Marcus SM. Hypertensive crisis from herbal treatment of impotence. Am J Emerg Med. 1999;17:317-318. PubMed
  59. Wylie KR. Yohimbine and sinusitis. Br J Psychiatry. 1996;169(3):384-5. PubMed
  60. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  61. Mueller-Schoell A, Michelet R, Weinelt F, Kloft C, Mikus G. CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications. Arch Toxicol. 2021. PubMed
  62. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
  63. Schmauss M, Laakmann G, Dieterle D. Effects of alpha 2-receptor blockade in addition to tricyclic antidepressants in therapy-resistant depression. J Clin Psychopharmacol. 1988;8(2):108-11.
  64. 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
  65. Hodapp B, Haggerty A, Feldman R, Timpe J. Intracranial hemorrhage after a single dose of Yohimbine in a chronic user of clonidine. Am J Emerg Med 2022;62:145. PubMed
  66. Vay M, Meyer MJ, Blank A, et al. Oral yohimbine as a new probe drug to predict CYP2D6 activity: results of a fixed-sequence phase I trial. Clin Pharmacokinet. 2020;59(7):927-939. PubMed

See these in context on the Yohimbe monograph →

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

See these in context on the Theacrine monograph →

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

See these in context on the Hordenine monograph →

Sulbutiamine 4 references
  1. Shah S. Adjuvant role of vitamin B analogue (sulbutiamine) with anti-infective treatment in infection associated asthenia. J Assoc Physicians India. 2003;51:891-5.
  2. Loo H, Poirier M, Ollat H, et al. [Effects of subutiamine (Arcalion 200) on psycho-behavioral inhibition in major depressive episodes]. Encephale. 2000;26(2):70-5.
  3. Kiew K, Wan Mohamad W, Ridzuan A, et al. Effects of sulbutiamine on diabetic polyneuropathy: an open randomized controlled study in type 2 diabetics. Malays J Med Sci. 2002;9(1):21-7.
  4. Sevim S, Kaleagasi H, Tasdelen B. Sulbutiamine shows promising results in reducing fatigue in patients with multiple sclerosis. Mult Scler Relat Disord. 2017;16:40-43. PubMed

See these in context on the Sulbutiamine monograph →

Lotus 5 references
  1. Yu, J. and Hu, W. S. [Effects of neferine on platelet aggregation in rabbits]. Yao Xue.Xue.Bao. 1997;32(1):1-4.
  2. Yang, J. and Zhou, K. NMR spectroscopic analysis of neferine and isoliensinine. Magn Reson.Chem 2004;42(11):994-997. PubMed
  3. Mukherjee, P. K., Saha, K., Balasubramanian, R., Pal, M., and Saha, B. P. Studies on psychopharmacological effects of Nelumbo nucifera Gaertn. rhizome extract. J Ethnopharmacol. 1996;54(2-3):63-67. PubMed
  4. Mukherjee, P. K., Saha, K., Pal, M., and Saha, B. P. Effect of Nelumbo nucifera rhizome extract on blood sugar level in rats. J Ethnopharmacol. 1997;58(3):207-213. PubMed
  5. Hiraguchi Y, Tokuda R, Gen M, et al. Identification of a novel food allergen in lotus root. Allergol Int. 2018;67(1):141-143. PubMed

See these in context on the Lotus monograph →

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

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