Major interaction on record — check this product against your medications before combining. Based on 15 of 18 ingredients. Check your meds →
Dietary supplement

PTF Tropical Punch Ingredients & Drug Interactions

by Gamma Labs

PTF Tropical Punch label
See full label image
Powder 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 PTF Tropical Punch 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

PTF Tropical Punch is a dietary supplement by Gamma Labs with 18 active ingredients. Its ingredients are commonly taken for high cholesterol, vitamin b3 deficiency (pellagra), heart health support.Based on those ingredients, 1,611 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Bacopa Extract 20%, Pomegranate powder, Vitamin E. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against PTF Tropical Punch by Gamma Labs

Ask about any prescription or over-the-counter medication and we check it for interactions with PTF Tropical Punch by Gamma Labs — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of PTF Tropical Punch by Gamma Labs

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 Sep 3, 2026

What’s inside

Partial disclosure
Ingredient Transparency · database check
Partial

Most active ingredients list an amount, but at least one is hidden in a blend or missing.

Why this rating?
  • The label discloses an exact amount for 9 of its 18 active ingredients.
  • “N-Acetyl Tyrosine” is listed as a grouped ingredient — the label doesn't break down how much of each component you get.
  • “Antioxidant Complex” is a proprietary blend — the label gives one combined amount (200 mg) without saying how much of each component you get.
  • “Energy And Focus Complex” is a proprietary blend — the label gives one combined amount (465 mg) without saying how much of each component you get.

PTF Tropical Punch contains 18 ingredients, including 11 active compounds and several proprietary blends. The active ingredients include B vitamins (niacin, B6, B12), vitamin C and E, L-tyrosine, acetyl-L-carnitine, caffeine, vinpocetine, pomegranate powder, Mucuna pruriens (which naturally contains levodopa), bacopa extract, ATP, huperzine A, and acai powder.

The product also contains inactive ingredients like citric acid, natural and artificial flavors, silica, sucralose, acesulfame potassium, and FD&C Red #40.

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: enhance workouts and physical performance.
  • We looked for evidence on: Athletic performance, Attention, Attention deficit-hyperactivity disorder (ADHD), Age-related cognitive decline, Anxiety, Alzheimer disease — and 3 related terms.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Huperzine A is rated "Possibly Effective" for Alzheimer disease.
  • Also on file: Acetyl-l-carnitine is rated "Possibly Effective" for Age-related cognitive decline, Alzheimer disease.

The evidence for this product's ingredients is mixed. Niacin is likely effective for pellagra and possibly effective for HIV/AIDS-related dyslipidemia and metabolic syndrome.

Vitamin B6 is effective for sideroblastic anemia and B6 deficiency, and possibly effective for pregnancy-related nausea. Vitamin E is effective for E deficiency and possibly effective for Alzheimer disease.

Vitamin C is effective for C deficiency and possibly effective for several conditions. Acetyl-L-carnitine, L-tyrosine, caffeine, and bacopa have limited or insufficient evidence for most claimed uses—caffeine is likely effective for mental alertness and athletic performance, but L-tyrosine is rated possibly ineffective for athletic performance.

Vinpocetine, pomegranate, Mucuna pruriens, ATP, and huperzine A all show insufficient or unclear evidence for their marketed benefits. The product's overall effectiveness for energy and focus relies on ingredients with unproven or weak supporting data.

The evidence, ingredient by ingredient Niacin Vitamin B6 Vitamin E Vitamin C Sodium Vitamin B12 Acai Pomegranate

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 15 of the 16 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 16 of 16.
  • General safety write-ups exist for 16 of 16.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated at normal doses, but several carry real risks at high amounts. Niacin commonly causes flushing and gastrointestinal upset, and at pharmacologic doses can harm the liver.

Vitamin B6 at high doses (above 1,000 mg daily) can damage nerves with prolonged use. Vitamin E may increase bleeding risk, especially at doses above 400 IU daily.

Caffeine can cause anxiety, insomnia, and jitteriness; the product's safety at any given dose depends on your total daily caffeine intake. Acetyl-L-carnitine may cause agitation, headache, and dry mouth.

Mucuna pruriens contains levodopa and carries risks of serious dopamine-related effects. Vinpocetine is not recommended in pregnancy.

Bacopa, huperzine A, and ATP supplements lack established long-term safety data. Niacin, vitamin B6, vitamin E, and vitamin C safety notes advise caution or avoidance of high-dose supplements in pregnancy; acetyl-L-carnitine, L-tyrosine, vinpocetine, Mucuna pruriens, ATP, huperzine A, and bacopa lack sufficient pregnancy safety data.

Regarding lactation, vitamin B12 and pomegranate are likely safe, but most others have limited or no data.

Side effects, ingredient by ingredient Niacin Vitamin B6 Vitamin E Vitamin C Sodium Vitamin B12 Acai Pomegranate

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?
  • 16 of the 16 matched ingredients can interact with medications — Vinpocetine, Pomegranate, Bacopa, Huperzine A, Acetyl-l-carnitine, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; lithium; Parkinson's medications.
  • For scale: 1,612 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, double-check your medications against these drug types. Most serious: caffeine with ephedrine (Major risk of dangerous stimulant effects).

Major concerns also include Mucuna pruriens with blood pressure medication (methyldopa, guanethidine), MAOIs, and levodopa itself. Moderate interactions span blood thinners and warfarin (from niacin, vitamin E, acetyl-L-carnitine, vinpocetine, pomegranate), antihypertensive drugs (niacin, vitamin B6, sodium, pomegranate), diabetes medications (niacin, acai), thyroid hormones (acetyl-L-carnitine, L-tyrosine, bacopa), seizure medications (vitamin B6, caffeine, carbamazepine via pomegranate and ATP), statins (niacin), and numerous others.

If you're on any of these, run your exact medications through the checker before starting.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glancePartially disclosed formula with clinical evidence supporting its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

PTF Tropical Punch is a multi-ingredient product aimed at energy and focus, but its active ingredients have weak or insufficient evidence for most of these claims. More importantly, it carries substantial medication interactions—particularly with blood thinners, blood pressure drugs, seizure meds, diabetes drugs, and certain psychiatric medications—and includes caffeine plus Mucuna pruriens (levodopa), which pose real risks if you're on certain prescriptions.

If you take any regular medications, check them against this page's interaction checker before you start. Talk with your doctor or pharmacist about whether this product is right for you.

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

Assessment coverage: 16 of 18 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Oct 25, 2012.

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 PTF Tropical Punch, straight from the product label.

Brand Gamma Labs
Barcode (UPC) 794504646801
Net contents 10.8 oz.; 306 Gram(s)
Market status On market
Date entered into DSLD Oct 25, 2012
DSLD ID 12456
Product type Other Combinations
Supplement form Powder
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 PTF Tropical Punch by Gamma Labs, 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:
7.65 Gram(s)
Maximum serving Sizes:
15.3 Gram(s)
Servings per container
40
UPC/BARCODE
794504646801
IngredientAmount% DV
Calories5 {Calories}--
Total Carbohydrates0.5 g1%
Niacin10 mg50%
Vitamin B65 mg250%
Vitamin E12.5 IU42%
Acetyl L-Carnitine0 NP--
L-Tyrosine0 NP--
Vitamin C0.5 g1%
Sodium39 mg1%
Vitamin B12125 mcg2083%
Caffeine150 mg--
Vinpocetine0 NP--
Acai powder0 NP--
N-Acetyl Tyrosine0 NP--
Antioxidant Complex200 mg--
Pomegranate powder0 NP--
Mucuna pruriens0 NP--
Energy And Focus Complex465 mg--
ATP0 NP--
Huperzine 5%0 NP--
Strength And Endurance Complex3500 mg--
N.O.Pump Complex2025 mg--
Bacopa Extract 20%0 NP--

Other ingredients: Citric Acid, Natural and Artificial flavors, Silica, Sucralose, Acesulfame Potassium, FD&C Red #40

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.
Suggested/Recommended/Usage/Directions

Directions: Consume 30 minutes before you train. To assess tolerance, add one serving (1 scoop) to 5-6 ounces of cold water. After determining tolerance and desired effect, take one or two servings (1-2 scoops) 30 minutes before training. Stir or shake well before using.

Storage

Store at 15-30(0)C (59-86(0)F). Protect from heat, light and moisture.

Precautions

Do not purchase if seal is broken.

WARNING: This product is intended to enhance workouts. Do not exceed recommended dose.

Not intended for use by persons under the age of 18 or those with a medical condition.

Do not use if you have high blood pressure or heart problems or are contemplating becoming pregnant.

Consult your physician before using this product if you are pregnant or nursing, or taking any medication.

General

V-P-0111011B

General Statements

33% MORE

CLINICALLY SUPERIOR PRE-TRANING FORMULA

Gamma Labs Pre-Training Formula (PTF) Was Developed to Enhance: - Energy and Performance Levels - Mental Focus, Concentration & Reaction Time - Strength & Endurance Levels - Nitric Oxide Levels for Maximum Pumps

Great Taste Fast Results No Crash

No Matter What Your Fitness Level, Gamma Labs PTF Has You Covered!

QUESTIONS OR COMMENTS CALL Tel (877) GAMMAO-2 (426-6262)

Seals/Symbols

GOOD MANUFACTURING PRACTICE GMP Certified

Formulation

No Banned Substances, All 100% Approved Gluten-Free

FDA Disclaimer Statement

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

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

See for yourself

PTF Tropical Punch by Gamma Labs label

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

PTF Tropical Punch 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 PTF Tropical Punch by Gamma Labs

These are the 18 active ingredients this product is made of. Select any to open its full monograph.

Serving size7.65 Gram(s) Dosage formPowder Servings per container40 Amounts shown are per serving.

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

Niacin

Interacts with
727 drugs
10 mg per serving

Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescr...

Niacin monograph & interactions

Vitamin B6

Interacts with
210 drugs
5 mg per serving Form: Pyridoxine Hydrochloride

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is b...

Vitamin B6 monograph & interactions

Vitamin E

Interacts with
764 drugs
12.5 IU per serving Form: D-Alpha-Tocopheryl Acetate

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

Vitamin E monograph & interactions

Vitamin C

Interacts with
207 drugs
0.5 g per serving Form: Ascorbic Acid

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for im...

Vitamin C monograph & interactions

Sodium

Interacts with
205 drugs
39 mg per serving Form: Sodium Chloride

Sodium is an essential mineral and electrolyte your body needs to balance fluids, support nerves, and help muscles work. Most people in modern diets g...

Sodium monograph & interactions

Vitamin B12

Interacts with
20 drugs
125 mcg per serving Form: Methylcobalamin

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very h...

Vitamin B12 monograph & interactions

Antioxidant Complex

200 mg per serving

Energy And Focus Complex

465 mg per serving

Strength And Endurance Complex

3500 mg per serving Form: CarnoSyn, Creatine Monohydrate, Di Creatine Malate, Magnesium Creatine Chelate, Taurine

N.O.Pump Complex

2025 mg per serving Form: Arginine AKG, Citrulline Malate, Glycerol, Guanipro(TM) Guanidino Propionic Acid, Gynostemma Pentaphyllium Extract, L-Arginine, L-Arginine Malate, L-Norvaline

Other (inactive) ingredients: Citric Acid, Natural and Artificial flavors, Silica, Sucralose, Acesulfame Potassium, FD&C Red #40. These complete the product’s ingredient list but are not active constituents.

Interaction report

PTF Tropical Punch by Gamma Labs Drug Interactions

Want to check YOUR meds against PTF Tropical Punch?

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
1,611Drugs
27 Major 1,565 Moderate 19 Minor

Ingredients driving the most interactions

Bacopa Extract 20% 930
Pomegranate powder 922
Vitamin E 764
Niacin 727
Huperzine 5% 219

Individual Drug Interactions

The ingredients in PTF Tropical Punch interact with 1,611 drugs. Click any drug to see the details.

15 of the 18 ingredients in PTF Tropical Punch interact with drugs. Each result below shows which ingredient is responsible. Bacopa Extract 20% Pomegranate powder Vitamin E Niacin Huperzine 5% Vitamin B6 Vinpocetine Vitamin C Sodium Acetyl L-Carnitine Mucuna pruriens Acai powder ATP L-Tyrosine Vitamin B12

Each ingredient & the kinds of drugs it affects

For each ingredient in PTF Tropical Punch 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.

Bacopa Extract 20%8 drug types · 930 drugs

Anticholinergic Drugs

Theoretically, concurrent use might decrease the effectiveness of both agents.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs. Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.

Likelihood Possible Evidence D
Cevimeline (Evoxac)

Theoretically, bacopa might increase the effects and adverse effects of cevimeline.
In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes. However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels. Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.
In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes. It is not known whether this is clinically significant.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.
Research on the effect of bacopa extracts on CYP2C9 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C9, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.
Research on the effects of bacopa extracts on CYP3A4 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and competitively inhibit CYP3A4, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, bacopa might have additive effects when used with thyroid hormone.
Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40%.

Likelihood Possible Evidence D
Bacopa Extract 20% full monograph & interactions

Pomegranate powder9 drug types · 922 drugs

Ace Inhibitors (Aceis)

Theoretically, taking pomegranate with ACEIs might increase the risk of adverse effects.
Pomegranate juice is thought to have ACE inhibitor-like effects.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking pomegranate with antihypertensive drugs might increase the risk of hypotension.
Consuming pomegranate juice can modestly lower blood pressure.

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

Theoretically, pomegranate might increase levels of drugs metabolized by CYP2D6.
In vitro, pomegranate juice inhibits CYP2D6. However, the clinical significance of this potential interaction in humans is not known.

Likelihood Possible Evidence D
Rosuvastatin (Crestor)

Theoretically, taking pomegranate with rosuvastatin might increase the risk of adverse effects.
In one case, a patient taking rosuvastatin 5 mg every other day in combination with ezetimibe 10 mg daily developed rhabdomyolysis after drinking pomegranate juice 200 mL twice weekly for 3 weeks. This patient had a history of elevated creatine kinase levels while not receiving any statin treatment. This suggests a possible underlying myopathy and predisposition to rhabdomyolysis.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, pomegranate might increase warfarin levels and increase the risk of bleeding. Also, discontinuing regular consumption of pomegranate juice might decrease warfarin levels.
In one case report, a patient had a stable, therapeutic bleeding time, as measured by international normalized ratio (INR), while taking warfarin in combination with pomegranate juice 2-3 times per week. The patient became subtherapeutic within about 10 days after discontinuing pomegranate juice, which required a warfarin dose increase. In another case report, a patient with a stable INR for over one year presented with an INR of 14. The patient noted no changes to medications or diet but did report consuming around 3 liters of pomegranate juice over the previous week. The patient's INR stabilized upon moderation of pomegranate juice consumption. The mechanism of this potential interaction is unclear.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, taking pomegranate with carbamazepine might increase the risk of adverse effects, although research suggests this interaction is unlikely to be clinically significant.
Animal research shows that pomegranate juice may inhibit cytochrome P450 3A4 (CYP3A4) metabolism of carbamazepine and increase levels of carbamazepine by 1.5 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP3A4, but might not inhibit hepatic CYP3A4. However, some human research suggests that pomegranate does not significantly inhibit CYP3A4 drug metabolism in humans.

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

Theoretically, pomegranate might increase levels of drugs metabolized by CYP2C9.
Some animal and in vitro research shows that pomegranate juice inhibits intestinal, but not hepatic, CYP2C9 isoenzyme activity. However, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans.

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

Theoretically, pomegranate might increase levels of drugs metabolized by CYP3A4, but most research suggests this interaction is unlikely to be clinically significant.
Pomegranate contains several polyphenols that have individually been shown to inhibit CYP3A4. However, there is contradictory evidence about the effect of whole pomegranate juice on CYP3A4 activity. In vitro, pomegranate juice significantly inhibits the CYP3A4 enzyme, with comparable inhibition to grapefruit juice. In an animal model, pomegranate juice inhibits CYP3A4 metabolism of carbamazepine and increases levels of carbamazepine by 1.5 times; however, in human volunteers, drinking a single glass of pomegranate juice 240 mL or taking 200 mL daily for 2 weeks does not significantly affect levels of the CYP3A4 substrate midazolam after oral or intravenous administration. Another study in healthy volunteers shows that consuming pomegranate juice 300 mL three times daily for three days also does not significantly affect levels of simvastatin, a CYP3A4 substrate This suggests that pomegranate is unlikely to significantly affect levels of CYP3A4 substrates in humans.

Likelihood Unlikely Evidence B
Tolbutamide (Orinase)

Theoretically, pomegranate might increase levels of tolbutamide, although research suggests this interaction is unlikely to be clinically significant.
Animal research shows that pomegranate juice inhibits the cytochrome P450 2C9 (CYP2C9) metabolism of tolbutamide. Pomegranate juice increased tolbutamide levels by 1.2 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP2C9, but might not inhibit hepatic CYP2C9. Despite this evidence, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans. This interaction does not appear to be clinically significant in humans.

Likelihood Unlikely Evidence D
Pomegranate powder full monograph & interactions

Vitamin E8 drug types · 764 drugs

Alkylating Agents

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

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence B
Antitumor Antibiotics

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

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

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

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

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

Likelihood Possible Evidence D
Selumetinib (Koselugo)

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

Likelihood Possible Evidence D
Warfarin (Coumadin)

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

Likelihood Possible Evidence B
Niacin

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

Likelihood Possible Evidence A
Vitamin E full monograph & interactions

Niacin15 drug types · 727 drugs

Alcohol (Ethanol)

Concomitant use of alcohol and niacin might increase the risk of flushing and hepatotoxicity.
Alcohol can exacerbate the flushing and pruritus associated with niacin. Large doses of niacin might also exacerbate liver dysfunction associated with chronic alcohol use. A case report describes delirium and lactic acidosis in a patient taking niacin 3 grams daily who ingested 1 liter of wine. Advise patients to avoid large amounts of alcohol while taking niacin.

Likelihood Probable Evidence D
Allopurinol (Zyloprim)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as allopurinol.
Large doses of niacin can reduce urinary excretion of uric acid, potentially resulting in hyperuricemia. Doses of uricosurics such as allopurinol might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Anticoagulant/Antiplatelet Drugs

Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.
Several cases of clotting factor synthesis deficiency and coagulopathy have been reported in patients taking sustained-release niacin. Also, thrombocytopenia has been reported in patients treated with niacin or niacin plus lovastatin.

Likelihood Possible Evidence D
Antidiabetes Drugs

Niacin can increase blood glucose levels and may diminish the effects of antidiabetes drugs.
Niacin impairs glucose tolerance in a dose-dependent manner, probably by causing or aggravating insulin resistance and increasing hepatic production of glucose. In diabetes patients, niacin 4.5 grams daily for 5 weeks can increase plasma glucose by an average of 16% and glycated hemoglobin (HbA1c) by 21%. However, lower doses of 1.5 grams daily or less appear to have minimal effects on blood glucose. In some patients, glucose levels increase when niacin is started, but then return to baseline when a stable dose is reached. Up to 35% of patients with diabetes may need adjustments in hypoglycemic therapy when niacin is added.

Likelihood Probable Evidence B
Antihypertensive Drugs

Theoretically, niacin may increase the risk of hypotension when used with antihypertensive drugs.
The vasodilating effects of niacin can cause hypotension. Furthermore, some clinical evidence suggests that a one-hour infusion of niacin can reduce systolic, diastolic, and mean blood pressure in hypertensive patients. This effect is not observed in normotensive patients.

Likelihood Possible Evidence B
Bile Acid Sequestrants

Bile acid sequestrants can bind niacin and decrease absorption. Separate administration by 4-6 hours to avoid an interaction.
In vitro studies show that colestipol (Colestid) binds about 98% of available niacin and cholestyramine (Questran) binds 10% to 30%.

Likelihood Possible Evidence D
Gemfibrozil (Lopid)

Theoretically, concomitant use of niacin and gemfibrozil might increase the risk of myopathy in some patients.
A case of myopathy from concomitant use of niacin and gemfibrozil has been reported. Niacin alone has also been associated with cases of myopathy. Using gemfibrozil with niacin might further increase the risk of developing myopathy.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.
Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses. Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin.

Likelihood Possible Evidence D
Hmg-Coa Reductase Inhibitors ("Statins")

Theoretically, concomitant use of niacin and statins might increase the risk of myopathy and rhabdomyolysis in some patients.
Some case reports have raised concerns that niacin might increase the risk of myopathy and rhabdomyolysis when combined with statins. However, a significantly increased risk of myopathy has not been demonstrated in clinical trials, including those using an FDA-approved combination of lovastatin and niacin (Advicor).

Likelihood Possible Evidence D
Probenecid (Benemid)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as probenecid.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as probenecid might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Sulfinpyrazone (Anturane)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as sulfinpyrazone.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as sulfinpyrazone might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Thyroid Hormone

Theoretically, niacin might antagonize the therapeutic effects of thyroid hormones.
Clinical research and case reports suggests that taking niacin can reduce serum levels of thyroxine-binding globulin by up to 25% and moderately reduce levels of thyroxine (T4). Patients taking thyroid hormone for hypothyroidism might need dose adjustments when using niacin.

Likelihood Probable Evidence D
Transdermal Nicotine (Nicoderm)

Theoretically, concomitant use of niacin and transdermal nicotine might increase the risk of flushing and dizziness.
Niacin and nicotine can both cause flushing and dizziness.

Likelihood Possible Evidence D
Warfarin (Coumadin)

There is limited evidence that niacin may increase the anticoagulant effects of warfarin.
In a case report, a patient on warfarin developed an elevated international normalized ratio (INR) of 3.9 after taking niacin for two weeks. The patient's INR was previously stable, ranging between 2 and 3 in recent months, and no other medication changes were identified. The elevated INR returned to therapeutic range within 4 days following the discontinuation of niacin.

Likelihood Possible Evidence D
Aspirin

Large doses of aspirin might alter the clearance of niacin.
Aspirin is often used with niacin to reduce niacin-induced flushing. Doses of 80-975 mg aspirin have been used, but 325 mg appears to be optimal. Aspirin also seems to reduce the clearance of niacin by competing for glycine conjugation. Taking aspirin 1 gram seems to reduce niacin clearance by 45%. This is probably a dose-related effect and not clinically significant with the more common aspirin dose of 325 mg.

Likelihood Likely Evidence B
Niacin full monograph & interactions

Huperzine 5%2 drug types · 219 drugs

Anticholinergic Drugs

Theoretically, huperzine A might decrease the effects of anticholinergic drugs.
Huperzine A has acetylcholinesterase (AChE) inhibiting effects. In animal models, huperzine A reversed cognitive deficits induced by scopolamine, an anticholinergic drug.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, concurrent use of huperzine A with cholinergic drugs might increase the effects and side effects of these medications.
Huperzine A can inhibit acetylcholinesterase (AChE) and might cause cumulative effects if used with cholinergic drugs.

Likelihood Possible Evidence B
Huperzine 5% full monograph & interactions

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Levodopa

Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.

Likelihood Unlikely Evidence D
Vitamin B6 full monograph & interactions

Vinpocetine3 drug types · 208 drugs

Anticoagulant/Antiplatelet Drugs

Vinpocetine might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Clinical research shows that vinpocetine decreases red blood cell aggregation, as well as plasma and whole blood viscosity. This effect has been seen with intravenous vinpocetine 1 mg/kg and oral vinpocetine 30 mg daily. Vinpocetine also seems to have antiplatelet effects.

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

Theoretically, vinpocetine might increase levels of drugs metabolized by CYP2C9.
In vitro research shows that vinpocetine weakly inhibits CYP2C9. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Vinpocetine might modestly increase the risk of bleeding when taken with warfarin.
Clinical research shows that the combination of warfarin and vinpocetine leads to slight increases in prothrombin time and the area under the concentration curve for warfarin. However, these increases were small, and researchers suggest that this interaction is not likely to be clinically significant in most patients.

Likelihood Possible Evidence B
Vinpocetine full monograph & interactions

Vitamin C13 drug types · 207 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Aluminum

Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption. In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely. Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

Likelihood Probable Evidence B
Antitumor Antibiotics

Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Estrogens

Vitamin C might increase blood levels of estrogens.
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements. Monitor these patients for estrogen-related side effects.

Likelihood Probable Evidence B
Fluphenazine (Prolixin)

Theoretically, vitamin C might decrease levels of fluphenazine.
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started. The mechanism is not known, and there is no further data to confirm this interaction.

Likelihood Possible Evidence D
Indinavir (Crixivan)

Vitamin C can modestly reduce indinavir levels.
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Vitamin C can increase levothyroxine absorption.
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH.

Likelihood Probable Evidence B
Warfarin (Coumadin)

High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption. There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time. Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant. However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

High-dose vitamin C might slightly prolong the clearance of acetaminophen.
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases. This effect is not likely to be clinically significant.

Likelihood Probable Evidence B
Aspirin

Acidification of the urine by vitamin C might increase aspirin levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction is not clinically significant.

Likelihood Possible Evidence B
Choline Magnesium Trisalicylate (Trilisate)

Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Niacin

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

Likelihood Possible Evidence A
Salsalate (Disalcid)

Acidification of the urine by vitamin C might increase salsalate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Vitamin C full monograph & interactions

Sodium7 drug types · 205 drugs

Antihypertensive Drugs

Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.
High intake of dietary sodium can increase systolic and diastolic blood pressure. Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease.

Likelihood Probable Evidence A
Corticosteroids

Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.
Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone.

Likelihood Possible Evidence D
Didanosine (Videx)

Concomitant use of didanosine with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia.
Didanosine formulations contain a significant amount of sodium.

Likelihood Probable Evidence C
Lithium

Altering dietary intake of sodium might alter the levels and clinical effects of lithium.
High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion. Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate. Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L. Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

Likelihood Probable Evidence B
Sodium Phosphates

Theoretically, concomitant use of sodium phosphate with sodium supplements might increase the risk of hypernatremia.
Use of high doses (> 45 mL in 24 hours) of sodium phosphate, such as those used for bowel cleansing before surgery, can lead to serious electrolyte disturbances, including hypernatremia. The risk of hypernatremia is highest in the elderly and people with other risk factors for electrolyte disturbances.

Likelihood Possible Evidence D
Sodium-Containing Drugs

Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.
The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population. Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

Likelihood Possible Evidence D
Tolvaptan (Samsca)

Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.
Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia. Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

Likelihood Probable Evidence C
Sodium full monograph & interactions

Acetyl L-Carnitine4 drug types · 203 drugs

Acenocoumarol (Sintrom)

Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.
L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is similar to warfarin, but shorter-acting. There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product. It is unclear if such an interaction would also occur with acetyl-L-carnitine.

Likelihood Possible Evidence D
Serotonergic Drugs

Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.
Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.
L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells. Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism. It is unclear if such an interaction would occur with acetyl-L-carnitine.

Likelihood Probable Evidence B
Warfarin (Coumadin)

Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin.
L-carnitine, the parent compound of acetyl-L-carnitine, might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin. There is not enough information to know whether this interaction occurs with acetyl-L-carnitine and warfarin.

Likelihood Possible Evidence D
Acetyl L-Carnitine full monograph & interactions

Mucuna pruriens8 drug types · 193 drugs

Levodopa

Concomitant use can increase the risk of levodopa-related adverse effects.
Cowhage contains levodopa. Some cowhage products have been standardized to contain 75-400 mg of levodopa per dose.

Likelihood Likely Evidence D
Methyldopa (Aldomet)

Theoretically, concomitant use of cowhage and methyldopa might increase the risk of hypotension.
Cowhage contains levodopa. Use of levodopa with methyldopa might cause additive hypotension. In addition, methyldopa may inhibit peripheral decarboxylation of levodopa and increase levodopa levels in the central nervous system; avoid using.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use of cowhage and non-selective MAOIs might increase the risk of hypertensive crisis.
Cowhage contains levodopa. Use of levodopa with non-selective MAOIs might cause hypertensive crisis. However, this interaction has not been reported with MAO-B selective inhibitors such as selegiline.

Likelihood Probable Evidence D
Anesthesia

Theoretically, concomitant use of cowhage and anesthesia might increase the risk of arrhythmias.
Cowhage contains levodopa. Use of levodopa with cyclopropane or halogenated hydrocarbon anesthesia has led to arrhythmias. Other anesthetics have not been implicated. Use other anesthetics in patients taking cowhage or tell patients to stop taking cowhage at least 2 weeks before surgery.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, concomitant use of cowhage and antidiabetes drugs might increase the risk of hypoglycemia.
Animal research shows that cowhage might have hypoglycemic effects.

Likelihood Possible Evidence D
Antipsychotic Drugs

Theoretically, use of cowhage might decrease the clinical effects of antipsychotic drugs.
Cowhage contains levodopa. Use of levodopa might counteract the antidopaminergic effects of antipsychotic medications.

Likelihood Possible Evidence D
Guanethidine (Ismelin)

Theoretically, concomitant use of cowhage and guanethidine might increase the risk of hypotension.
Cowhage contains levodopa. Use of levodopa with guanethidine might cause additive hypotension; avoid using.

Likelihood Probable Evidence D
Tricyclic Antidepressants (Tcas)

Theoretically, use of TCAs might reduce the levels and clinical effects of cowhage.
Cowhage contains levodopa. Use of TCAs might reduce the absorption of levodopa. Some case reports describe patients that developed hypertension and dyskinesia when taking both levodopa and TCAs.

Likelihood Possible Evidence D
Mucuna pruriens full monograph & interactions

Acai powder1 drug type · 86 drugs

Antidiabetes Drugs

Theoretically, taking acai with antidiabetes drugs might interfere with glycemic control.
Preliminary clinical research in healthy adults has shown that taking acai may increase or decrease levels of fasting blood glucose.

Likelihood Possible Evidence D
Acai powder full monograph & interactions

ATP3 drug types · 47 drugs

Dipyridamole (Persantine)

Dipyridamole can increase the therapeutic and toxic effects of adenosine.
Dipyridamole decreases the metabolism of adenosine. Intravenous infusion of adenosine in patients who are taking dipyridamole can cause dizziness, bradycardia, and syncope. Dipyridamole should be discontinued for several days prior to a cardiac stress test using adenosine.

Likelihood Likely Evidence D
Carbamazepine (Tegretol)

Carbamazepine might increase the risk of heart block when used concomitantly with adenosine.
Carbamazepine and adenosine can both cause heart block. Giving them concurrently might produce an additive effect.

Likelihood Possible Evidence D
Methylxanthines

Methylxanthines are competitive antagonists of adenosine and can block its pharmacologic effects.
The methylxanthines, aminophylline, caffeine, and theophylline, can block the effects of adenosine by acting as competitive antagonists at adenosine cell surface receptors. It is recommended that methylxanthines be avoided for 24 hours prior to cardiac stress tests.

Likelihood Possible Evidence D
ATP full monograph & interactions

L-Tyrosine2 drug types · 21 drugs

Levodopa

Theoretically, tyrosine might decrease the effectiveness of levodopa.
Tyrosine and levodopa compete for absorption in the proximal duodenum by the large neutral amino acid (LNAA) transport system. Advise patients to separate doses of tyrosine and levodopa by at least 2 hours.

Likelihood Probable Evidence D
Thyroid Hormone

Theoretically, tyrosine might have additive effects with thyroid hormone medications.
Tyrosine is a precursor to thyroxine and might increase levels of thyroid hormones.

Likelihood Probable Evidence D
L-Tyrosine full monograph & interactions

Vitamin B121 drug type · 20 drugs

Metformin (Glucophage)

Metformin, a common medication used to manage type 2 diabetes, has been associated with lower vitamin B12 levels in some individuals. Prolonged use of metformin can interfere with the absorption of B12 in the digestive system, potentially leading to a deficiency in this essential vitamin.

Likelihood Possible Evidence A
Vitamin B12 full monograph & interactions
The maker

Brand information

Manufacturer and brand details for PTF Tropical Punch, from the product label.

Gamma Labs

See all Gamma Labs products
Name
Gamma Labs.
City
West Babylon
State
NY
ZipCode
11704
Pharmacist Counseling Corner

PTF Tropical Punch by Gamma Labs: Common Questions

Does PTF Tropical Punch by Gamma Labs interact with any medications?
Yes. Based on its ingredients, PTF Tropical Punch has a known interaction with 1,611 medications, including 27 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
PTF Tropical Punch contains 18 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 this product have caffeine, and how much?
Yes, caffeine is listed as an active ingredient. The product facts don't specify the exact dose per serving, so check the label or contact the manufacturer for the precise amount. This matters because caffeine interacts with several drugs and builds up if you consume other caffeinated products.
Is it safe to take this while I'm on blood pressure medication?
Multiple ingredients—niacin, vitamin B6, sodium, and pomegranate—may lower blood pressure, which could cause too much of a drop when combined with your medication. Additionally, Mucuna pruriens in this product is a serious concern with certain blood pressure drugs like methyldopa and guanethidine. Talk with your doctor or pharmacist before you start to make sure it's safe for your specific medication.
Can I take this while pregnant or breastfeeding?
Safety data is limited for most ingredients. Niacin, vitamin B6, and vitamin E advise caution with high-dose supplements in pregnancy; Mucuna pruriens and vinpocetine are not recommended in pregnancy. For breastfeeding, Mucuna pruriens and several others lack safety data. Talk with your doctor or pharmacist about whether it's appropriate for your situation.
What are the common side effects?
Caffeine can cause anxiety, insomnia, jitteriness, and nausea. Niacin often causes flushing (burning, tingling, redness of the face and neck) and gastrointestinal upset like nausea or heartburn. Acetyl-L-carnitine may cause agitation, headache, or dry mouth. Bacopa can cause nausea, headache, and diarrhea. If you develop serious side effects or ones that don't stop, talk with your doctor.
Does this product actually boost energy and focus?
Caffeine and L-tyrosine are likely effective for mental alertness and athletic performance, but most other ingredients lack strong evidence for energy or focus. Niacin, acetyl-L-carnitine, vitamin B6, and bacopa all show insufficient or weak supporting data for cognitive or energy benefits in the research we hold.
What if I'm taking warfarin or another blood thinner?
Multiple ingredients in this product—niacin, vitamin E, acetyl-L-carnitine, vinpocetine, and pomegranate—can increase bleeding risk when combined with blood thinners like warfarin. This is a serious concern. Do not start this product without checking with your doctor or pharmacist first.

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

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Go deeper

The Full Monographs Behind PTF Tropical Punch’s Ingredients

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

Herb & supplement monograph

Niacin

Interacts with 727 drugs

Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescription-strength niacin has been used to...

Read the full Niacin monograph → Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-rel...

Read the full Vitamin B6 monograph → Herb & supplement monograph

Vitamin E

Interacts with 764 drugs

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

Read the full Vitamin E monograph → Herb & supplement monograph

Vitamin C

Interacts with 207 drugs

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for immune function, collagen, and acts as an...

Read the full Vitamin C monograph → Herb & supplement monograph

Sodium

Interacts with 205 drugs

Sodium is an essential mineral and electrolyte your body needs to balance fluids, support nerves, and help muscles work. Most people in modern diets get more than enough—often too much—from...

Read the full Sodium monograph → Herb & supplement monograph

Vitamin B12

Interacts with 20 drugs

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very helpful for people who are deficient — su...

Read the full Vitamin B12 monograph → Herb & supplement monograph

Acai

Interacts with 86 drugs

Acai is a nutritious Amazonian berry rich in antioxidants and healthy fats, and it is fine to enjoy as a food. However, strong human evidence is lacking for the bold health claims often atta...

Read the full Acai monograph → Herb & supplement monograph

Pomegranate

Interacts with 922 drugs

Pomegranate is a nutrient-rich fruit that is high in antioxidants and is widely enjoyed as food and juice. Early research suggests it may support heart health and blood pressure, but the evi...

Read the full Pomegranate monograph → Herb & supplement monograph

Acetyl-l-carnitine

Interacts with 203 drugs

Acetyl-L-carnitine is a form of the amino acid carnitine that the body uses to help produce energy in cells. It is most studied for nerve pain and memory-related conditions, though the evide...

Read the full Acetyl-l-carnitine monograph → Herb & supplement monograph

Tyrosine

Interacts with 21 drugs

L-tyrosine is an amino acid your body uses to make brain chemicals like dopamine and norepinephrine. Some studies suggest it may help mental performance during short-term stress, sleep loss,...

Read the full Tyrosine monograph → Herb & supplement monograph

Vinpocetine

Interacts with 208 drugs

Vinpocetine is a lab-made compound based on a chemical from the periwinkle plant, and it is marketed mainly for memory and brain health. The evidence behind these uses is limited and not str...

Read the full Vinpocetine monograph → Herb & supplement monograph

Cowhage

Interacts with 193 drugs

Cowhage (Mucuna pruriens) is a tropical legume best known as a natural source of L-dopa, the compound the body turns into dopamine. It is most studied for Parkinson's disease symptoms and ma...

Read the full Cowhage monograph → Herb & supplement monograph

Adenosine

Interacts with 47 drugs

Adenosine is a natural building block your body uses for energy and cell signaling, and a prescription injectable version is used by doctors to treat certain fast heart rhythms. As an over-t...

Read the full Adenosine monograph → Herb & supplement monograph

Huperzine A

Interacts with 219 drugs

Huperzine A is a purified compound from a Chinese clubmoss that acts like a mild cholinesterase inhibitor, similar in mechanism to some prescription Alzheimer's drugs. Some small studies sug...

Read the full Huperzine A monograph → Herb & supplement monograph

Bacopa

Interacts with 930 drugs

Bacopa is an Ayurvedic herb most often used for memory and thinking. Some small studies suggest it may modestly help memory when taken regularly for several weeks, but the evidence is limite...

Read the full Bacopa monograph →
Sources

Sources & How We Checked

PTF Tropical Punch'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 646 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.

Niacin 66 references
  1. Garg R, Malinow MR, Pettinger M, et al. Niacin treatment increases plasma homocysteine levels. Am Heart J 1999;138:1082-7.
  2. Anon. Inositol hexaniacinate. Altern Med Rev 1998;3:222-3.
  3. Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32. PubMed
  4. Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group. Arch Intern Med 2000;160:1177-84. PubMed
  5. Gibbons LW, Gonzalez V, Gordon N, Grundy S. The prevalence of side effects with regular and sustained-release nicotinic acid. Am J Med 1995;99:378-85. PubMed
  6. Whelan AM, Price SO, Fowler SF, Hainer BL. The effect of aspirin on niacin-induced cutaneous reactions. J Fam Pract 1992;34:165-8.
  7. Jungnickel PW, Maloley PA, Vander Tuin EL, et al. Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions. J Gen Intern Med 1997;12:591-6. PubMed
  8. Capuzzi DM, Guyton JR, Morgan JM, et al. Efficacy and safety of an extended-release niacin (Niaspan): a long-term study. Am J Cardiol 1998;82:74-81;disc. 85U-6U. PubMed
  9. Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252-8. PubMed
  10. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271:672-7. DOI
  11. Knopp RH, Alagona P, Davidson M, et al. Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Metabolism 1998;47:1097-104. PubMed
  12. Knopp RH. Clinical profiles of plain versus sustained-release niacin (Niaspan) and the physiologic rationale for nighttime dosing. Am J Cardiol 1998;82:24U-28U;discussion 39U-41U. PubMed
  13. Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 1990;264:723-6. DOI
  14. Leighton RF, Gordon NF, Small GS, et al. Dental and gingival pain as side effects of niacin therapy. Chest 1998;114:1472-4. PubMed
  15. American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9. DOI
  16. Vega GL, Grundy SM. Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Arch Intern Med 1994;154:73-82. DOI
  17. Guyton JR, Goldberg AC, Kreisberg RA, et al. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol 1998;82:737-43.
  18. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  19. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  20. Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71. PubMed
  21. Rader JI, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992;92:77-81. PubMed
  22. Kahn SE, Beard JC, Schwartz MW, et al. Increased B-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. Diabetes 1989;38:562-8.
  23. Schwartz ML. Severe reversible hyperglycemia as a consequence of niacin therapy. Arch Int Med 1993;153:2050-2. DOI
  24. Raising HDL and Niacin Use. Pharmacist's Letter/Prescriber's Letter 2004;20(5):200504.
  25. McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705. PubMed
  26. Reaven P, Witztum JL. Lovastatin, nicotinic acid and rhabdomyolysis (letter). Ann Int Med 1988;109:597-8. PubMed
  27. Ito MK. Advances in the understanding and management of dyslipidemia: using niacin-based therapies. Am J Health-Syst Pharm 2003;60(suppl 2):s15-21. PubMed
  28. Schwab RA, Bachhuber BH. Delirium and lactic acidosis caused by ethanol and niacin coingestion. Am J Emerg Med 1991;9:363-5. PubMed
  29. Product information: Niaspan. Kos Pharmaceuticals. Cranbury, NJ. 2005. Available at www.niaspan.com/professional/content/pdfs/productinfo.pdf. (Accessed 3 March 2006).
  30. Ding RW, Kolbe K, Merz B, et al. Pharmacokinetics of nicotinic acid-salicylic acid interaction. Clin Pharmacol Ther 1989;46:642-7. PubMed
  31. NIH News. NIH stops clinical trial on combination cholesterol treatment. May 26, 2011. http://www.nih.gov/news/health/may2011/nhlbi-26.htm. (Accessed 3 June 2011).
  32. Dearing BD, Lavie CJ, Lohmann TP, Genton E. Niacin-induced clotting factor synthesis deficiency with coagulopathy. Arch Intern Med. 1992;152(4):861-3. DOI
  33. O'Brien T, Silverberg JD, Nguyen TT. Nicotinic acid-induced toxicity associated with cytopenia and decreased levels of thyroxine-binding globulin. Mayo Clin Proc. 1992;67(5):465-8. PubMed
  34. Gadegbeku CA, Dhandayuthapani A, Shrayyef MZ, Egan BM. Hemodynamic effects of nicotinic acid infusion in normotensive and hypertensive subjects. Am J Hypertens. 2003;16(1):67-71. PubMed
  35. Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health Syst Pharm. 1995;52(15):1639-45. PubMed
  36. Litin SC, Anderson CF. Nicotinic acid-associated myopathy: a report of three cases. Am J Med. 1989;86(4):481-3. PubMed
  37. Dunn RT, Ford MA, Rindone JP, Kwiecinski FA. Low-Dose Aspirin and Ibuprofen Reduce the Cutaneous Reactions Following Niacin Administration. Am J Ther. 1995;2(7):478-480. PubMed
  38. Cashin-Hemphill L, Spencer CA, Nicoloff JT, et al. Alterations in serum thyroid hormonal indices with colestipol-niacin therapy. Ann Intern Med. 1987;107(3):324-9. PubMed
  39. Drinka PJ. Alterations in thyroid and hepatic function tests associated with preparations of sustained-release niacin. Mayo Clin Proc. 1992;67(12):1206. PubMed
  40. Shakir KM, Kroll S, Aprill BS, Drake AJ 3rd, Eisold JF. Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state. Mayo Clin Proc. 1995;70(6):556-8. PubMed
  41. Etchason JA, Miller TD, Squires RW, et al. Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin. Mayo Clin Proc. 1991;66(1):23-8. PubMed
  42. Henkin Y, Johnson KC, Segrest JP. Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin. JAMA. 1990;264(2):241-3. DOI
  43. Henkin Y, Oberman A, Hurst DC, Segrest JP. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med. 1991;91(3):239-46. PubMed
  44. Brown BG, Bardsley J, Poulin D, et al. Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease. Am J Cardiol. 1997;80(2)
  45. Goldberg A, Alagona P Jr, Capuzzi DM, et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol. 2000;85(9):1100-5. PubMed
  46. Aronov DM, Keenan JM, Akhmedzhanov NM, et al. Clinical trial of wax-matrix sustained-release niacin in a Russian population with hypercholesterolemia. Arch Fam Med. 1996;5(10):567-75. PubMed
  47. Morgan JM, Capuzzi DM, Guyton JR, et al. Treatment Effect of Niaspan, a Controlled-release Niacin, in Patients With Hypercholesterolemia: A Placebo-controlled Trial. J Cardiovasc Pharmacol Ther. 1996;1(3):195-202. PubMed
  48. Andersson RG, Aberg G, Brattsand R, Ericsson E, Lundholm L. Studies on the mechanism of flush induced by nicotinic acid. Acta Pharmacol Toxicol (Copenh). 1977 Jul;41(1):1-10. PubMed
  49. Brown WV. Niacin for lipid disorders. Indications, effectiveness, and safety. Postgrad Med. 1995 Aug;98(2):185-9, 192-3. PubMed
  50. O'REILLY PO, CALLBECK MJ, HOFFER A. Sustained-release nicotinic acid (nicospan); effect on (1) cholesterol levels and (2) leukocytes. Can Med Assoc J. 1959;80(5):359-62.
  51. Gharavi AG, Diamond JA, Smith DA, Phillips RA. Niacin-induced myopathy. Am J Cardiol. 1994;74(8):841-2. PubMed
  52. Litin SC, Anderson CF. Nicotinic acid-associated myopathy: a report of three cases. Am J Med. 1989;86(4):481-3. PubMed
  53. Fraunfelder FW, Fraunfelder FT, Illingworth DR. Adverse ocular effects associated with niacin therapy. Br J Ophthalmol 1995;79:54-56. PubMed
  54. Ali EH, McJunkin B, Jubelirer S, Hood W. Niacin induced coagulopathy as a manifestation of occult liver injury. W V Med J. 2013 Jan-Feb;109(1):12-4
  55. Aramwit P, Srisawadwong R, Supasyndh O. Effectiveness and safety of extended-release nicotinic acid for reducing serum phosphorus in hemodialysis patients. J Nephrol. 2012 May-Jun;25(3):354-62. PubMed
  56. Bassan M. A case for immediate-release niacin. Heart Lung. 2012 Jan-Feb;41(1):95-8. PubMed
  57. Davidson MH, Rooney M, Pollock E, Drucker J, Choy Y. Effect of colesevelam and niacin on low-density lipoprotein cholesterol and glycemic control in subjects with dyslipidemia and impaired fasting glucose. J Clin Lipidol. 2013 Sep-Oct;7(5):423-32. PubMed
  58. Guyton JR, Fazio S, Adewale AJ, Jensen E, Tomassini JE, Shah A, Tershakovec AM. Effect of extended-release niacin on new-onset diabetes among hyperlipidemic patients treated with ezetimibe/simvastatin in a randomized controlled trial. Diabetes Care. 2012 PubMed
  59. Loebl T, Raskin S. A novel case report: acute manic psychotic episode after treatment with niacin. J Neuropsychiatry Clin Neurosci. 2013 Fall;25(4):E14. PubMed
  60. Teo KK, Goldstein LB, Chaitman BR, Grant S, Weintraub WS, Anderson DC, Sila CA, Cruz-Flores S, Padley RJ, Kostuk WJ, Boden WE; AIM-HIGH Investigators. Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the
  61. Goldie C, Taylor AJ, Nguyen P, McCoy C, Zhao XQ, Preiss D. Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomized controlled trials. Heart. 2016 Feb;102(3):198-203.
  62. Schandelmaier S, Briel M, Saccilotto R, Olu KK, Arpagaus A, Hemkens LG, Nordmann AJ. Niacin for primary and secondary prevention of cardiovascular events. Cochrane Database Syst Rev. 2017 Jun 14;6:CD009744. PubMed
  63. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018;71(22):2570-84. PubMed
  64. Song S, Lee CJ, Oh J, Park S, Kang SM, Lee SH. Effect of Niacin on Carotid Atherosclerosis in Patients at Low-Density Lipoprotein-Cholesterol Goal but High Lipoprotein (a) Level: a 2-Year Follow-Up Study. J Lipid Atheroscler. 2019;8(1):58-66. PubMed
  65. Kimura H, Umemori Y, Yuki D. Anaphylactic shock-like symptoms due to niacin overdose: A case report. J Dermatol 2022;49(8):e287-e288. PubMed
  66. Nawaz N, Mistretta T, Karime C, Lewis J, Wolf E. Cholestatic Drug-Induced Liver Injury in a Patient Taking High-Dose Niacin for Hyperlipidemia. J Investig Med High Impact Case Rep 2024;12:23247096231224349. PubMed

See these in context on the Niacin monograph →

Vitamin B6 32 references
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
  4. South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  6. Baxter P, Aicardi J. Neonatal seizures after pyridoxine use. Lancet 1999;354:2082-3. PubMed
  7. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
  8. Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
  9. Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
  10. Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
  11. Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
  12. Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
  13. Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
  14. Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
  15. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
  16. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  17. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  18. Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
  19. Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
  20. de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
  21. Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
  22. Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
  23. Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
  24. Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
  25. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  26. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  27. Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
  28. Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
  29. Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
  30. Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
  31. Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
  32. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed

See these in context on the Vitamin B6 monograph →

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

See these in context on the Vitamin E monograph →

Acetyl-l-carnitine 22 references
  1. Thal LJ, Carta A, Clarke WR, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's Disease. Neurology 1996;47:705-11. PubMed
  2. Sano M, Bell K, Cote L, et al. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's Disease. Arch Neurol 1992;49:1137-41. PubMed
  3. Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's Disease. Neurology 1991;41:1726-32. PubMed
  4. Brooks JO 3rd, Yesavage JA, Carta A, Bravi D. Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. Int Psychoger 1998;10:193-203. PubMed
  5. Pettegrew JW, Klunk WE, Panchalingam K, et al. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging 1995;16:1-4. PubMed
  6. Rai G, Wright G, Scott L, et al. Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia. Curr Med Res Opin 1990;11:638-47. PubMed
  7. Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Meta
  8. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol 2003;18:61-71.. PubMed
  9. Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.
  10. Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database Syst Rev 2003;2:CD003158.. PubMed
  11. Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385. PubMed
  12. De Grandis D, Minardi C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D 2002;3:223-31. PubMed
  13. 12761 Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 2004;1033:158-67. PubMed
  14. Sima AAF, Calvani M, Mehra M, et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: An analysis of two randomized, placebo-controlled trials. Diabetes Care 2005;28:89-94.
  15. Youle, M. and Osio, M. A double-blind, parallel-group, placebo-controlled, multicentre study of acetyl L-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV.Med. 2007;8(4):241-250.
  16. Brennan BP, Jensen JE, Hudson JI, Coit CE, Beaulieu A, Pope HG Jr, Renshaw PF, Cohen BM. A placebo-controlled trial of acetyl-L-carnitine and a-lipoic acid in the treatment of bipolar depression. J Clin Psychopharmacol. 2013 Oct;33(5):627-35.
  17. Ledinek AH, Sajko MC, Rot U. Evaluating the effects of amantadin, modafinil and acetyl-L-carnitine on fatigue in multiple sclerosis--result of a pilot randomized, blind study. Clin Neurol Neurosurg. 2013 Dec;115 Suppl 1:S86-9. PubMed
  18. Martinotti G, Andreoli S, Reina D, Di Nicola M, Ortolani I, Tedeschi D, Fanella F, Pozzi G, Iannoni E, D'Iddio S, Prof LJ. Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects. Prog Neuropsychop PubMed
  19. Baek SM, Zheng R, Seo EJ, Hwang DY, Kim BH. Pharmacokinetic comparisons of two acetyl-L-carnitine formulations in healthy Korean volunteers. Int J Clin Pharmacol Ther. 2015;53(11):980-6. PubMed
  20. Goodison G, Overeem K, de Monte V, Siskind D. Mania associated with self-prescribed acetyl-l-carnitine in a man with bipolar I disorder. Australas Psychiatry. 2017;25(1):13-4.
  21. Bruno A, Pandolfo G, Crucitti M, Lorusso S, Zoccali RA, Muscatello MR. Acetyl-L-Carnitine Augmentation of Clozapine in Partial-Responder Schizophrenia: A 12-Week, Open-Label Uncontrolled Preliminary Study. Clin Neuropharmacol. 2016;39(6):277-80. PubMed
  22. Veronese N, Stubbs B, Solmi M, Ajnakina O, Carvalho AF, Maggi S. Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis. Psychosom Med. 2018;80(2):154-9. PubMed

See these in context on the Acetyl-l-carnitine monograph →

Tyrosine 4 references
  1. Meyer JS, Welch KM, Deshmukh VD, et al. Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease. J Amer Geriat Soc 1977;25:289-98.
  2. DiPiro JT, Talbert RL, Yee GC, et al; eds. Pharmacotherapy: A pathophysiologic approach. 4th ed. Stamford, CT: Appleton & Lange, 1999.
  3. Wood DR, Reimherr FW, Wender PH. Amino acid precursors for the treatment of attention deficit disorder, residual type. Psychopharmacol Bull 1985;21:146-9.
  4. van Spronsen FJ, van Rijn M, Bekhof J. Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets. Am J Clin Nutr 2001;73:153-7. PubMed

See these in context on the Tyrosine monograph →

Vitamin C 51 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
  3. Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
  4. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  5. Dwyer JH, Merz NB, Shirocre AM, et al. Progression of early atherosclerosis and intake of vitamin C and vitamin E from supplements and food. The Los Angeles Atherosclerosis Study. 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevent
  6. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. PubMed
  7. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  8. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  9. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  10. Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21. PubMed
  11. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  12. Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671. DOI
  13. Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479. DOI
  14. Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166. DOI
  15. Traxer O, Huet B, Poindexter J, et al. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003;170:397-401.. PubMed
  16. Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.
  17. Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601. PubMed
  18. Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7. PubMed
  19. Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413. DOI
  20. Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31. PubMed
  21. Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008. DOI
  22. Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35. PubMed
  23. Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70. PubMed
  24. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  25. Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7. PubMed
  26. Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6. PubMed
  27. Lee DH, Folsom AR, Harnack L, et al. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr 2004;80:1194-200. PubMed
  28. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15:3225-32. PubMed
  29. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  30. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  31. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  32. Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.
  33. Gruenwald, J., Graubaum, H. J., Busch, R., and Bentley, C. Safety and tolerance of ester-C compared with regular ascorbic acid. Adv.Ther. 2006;23(1):171-178.
  34. Rahimi, R., Nikfar, S., Rezaie, A., and Abdollahi, M. A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens.Pregnancy. 2009;28(4):417-434. PubMed
  35. Einerson, B., Nathorn, C., Kitiyakara, C., Sirada, M., and Thamlikitkul, V. The efficacy of ascorbic acid in suboptimal responsive anemic hemodialysis patients receiving erythropoietin: a meta-analysis. J Med.Assoc.Thai. 2011;94 Suppl 1:S134-S146.
  36. Li, G., Li, L., Yu, C., and Chen, L. Effect of vitamins C and E supplementation on Helicobacter pylori eradication: a meta-analysis. Br.J Nutr 2011;106(11):1632-1637.
  37. Chen X, Shen L, Gu X, et al. High-dose supplementation with vitamin C--induced pediatric urolithiasis: the first case report in a child and literature review. Urology. 2014;84(4):922-4. PubMed
  38. Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6. PubMed
  39. Yaich S, Chaabouni Y, Charfeddine K, et al. Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014;25(1):113-6. PubMed
  40. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  41. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004072. PubMed
  42. Seo MS, Kim JK, Shim JY. High-dose vitamin C promotes regression of multiple pulmonary metastases originating from hepatocellular carcinoma. Yonsei Med J. 2015;56(5):1449-52. PubMed
  43. Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403. PubMed
  44. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic acid supplements and kidney stones incidence among men and women: a systematic review and meta-analysis. Urol J. 2019;16(2):115-120.
  45. Thomas S, Patel D, Bittel B, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2 PubMed
  46. Giffen MA, McLemore JL. Hyperoxalosis Secondary to Intravenous Vitamin C Administration as a Non-Allopathic Treatment for Cancer. Acad Forensic Pathol 2019;9(1-2):118-126. PubMed
  47. Maike A, Sturgill D, Gallan A. Oxalate Nephropathy in a Renal Transplant Recipient After Receiving High Dose Ascorbic Acid. Am J Med Sci 2021. PubMed
  48. Shen ZY, Chen YR, Wang MC, Chang SS. High-dose vitamin C-induced acute oxalate nephropathy in a renal transplant recipient: a case report and literature review. Asian J Surg 2022. PubMed
  49. Yanase F, Spano S, Maeda A, et al. Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial. Crit Care 2023;27(1):371. PubMed
  50. Sharma Y, Sumanadasa S, Shahi R, et al. Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis. Sci Rep 2024;14(1):11846. PubMed
  51. Pejcic AV, Petrovic NZ, Djordjic MD, Milosavljevic MN. Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis. Balkan Med J 2024;41(4):248-260. PubMed

See these in context on the Vitamin C monograph →

Sodium 38 references
  1. Garabedian-Ruffalo SM, Ruffalo RL. Drug and nutrient interactions. Am Fam Physician 1986;33:165-74.
  2. Food and Drug Administration Science Background: Safety of Sodium Phosphates Oral Solution. September 17, 2001. Available at: http://www.fda.gov/cder/drug/safety/sodiumphospate.htm
  3. Coton T, Mallaret C, Coilliot C, Carre D, Guisset M. Severe acute ulcerated gastritis induced by salt. Presse Med 2009;38(3):499-500. PubMed
  4. Frings-Meuthen P, Buehlmeier J, Baecker N, et al. High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses. J Appl Physiol 2011;111(2):537-542. PubMed
  5. Frings-Meuthen P, Baecker N, Heer M. Low-grade metabolic acidosis may be the cause of sodium chloride-induced exaggerated bone resorption. J Bone Miner Res 2008;23(4):517-524. PubMed
  6. Alam S, Johnson AG. A meta-analysis of randomised controlled trials (RCT) among healthy normotensive and essential hypertensive elderly patients to determine the effect of high salt (NaCl) diet of blood pressure. J Hum Hypertens 1999;13(6):367-74.
  7. Boudville N, Ward S, Benaroia M, House AA. Increased sodium intake correlates with greater use of antihypertensive agents by subjects with chronic kidney disease. Am J Hypertens 2005;18(10):1300-5. PubMed
  8. Bennett WM. Drug interactions and consequences of sodium restriction. Am J Clin Nutr 1997;65(2 Suppl):678S-681S. PubMed
  9. Okusa MD, Crystal LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med 1994;97(4):383-9. PubMed
  10. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for water, potassium, sodium, chloride, and sulfate. Washington, DC: National Academy Press, 2005. Available at: http://www.nap.edu/openbook.php?record_id=10925. DOI
  11. D'Elia L, Rossi G, Ippolito R, Cappuccio FP, Strazzullo P. Habitual salt intake and risk of gastric cancer: a meta-analysis of prospective studies. Clin Nutr 2012;31(4):489-98. PubMed
  12. Goldsmith SR. Hyponatremia in heart failure: time for a trial. J Card Fail 2013;19(6):398-400. PubMed
  13. Willocks L, Brettle R, Keen J, Valentine C, Pinching AJ. Formulations of didanosine (ddI) and salt overload. Lancet 1992;339(8786):190.
  14. Chen L, Zhang Z, Chen W, Whelton PK, Appel LJ. Lower Sodium Intake and Risk of Headaches: Results From the Trial of Nonpharmacologic Interventions in the Elderly. Am J Public Health. 2016;106(7):1270-5. PubMed
  15. Cook NR, Appel LJ, Whelton PK. Lower levels of sodium intake and reduced cardiovascular risk. Circulation. 2014;129(9):981-9. PubMed
  16. Cook NR, Appel LJ, Whelton PK. Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention. J Am Coll Cardiol. 2016;68(15):1609-1617. PubMed
  17. Mente A, O'Donnell M, Rangarajan S, et al. Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies. Lancet. 2016;388(10043):465-75. PubMed
  18. Moosavian SP, Haghighatdoost F, Surkan PJ, Azadbakht L. Salt and obesity: a systematic review and meta-analysis of observational studies. Int J Food Sci Nutr. 2017;68(3):265-277. PubMed
  19. O'Donnell M, Mente A, Rangarajan S, et al. Urinary sodium and potassium excretion, mortality, and cardiovascular events. N Engl J Med. 2014;371(7):612-23. DOI
  20. Poggio R, Gutierrez L, Matta MG, Elorriaga N, Irazola V, Rubinstein A. Daily sodium consumption and CVD mortality in the general population: systematic review and meta-analysis of prospective studies. Public Health Nutr. 2015;18(4):695-704. PubMed
  21. Stallings VA, Harrison M, Oria M; Committee to Review the Dietary Reference Intakes for Sodium and Potassium, Food and Nutrition Board, Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine. Washington (DC): National Acad
  22. Mahtani KR, Heneghan C, Onakpoya I, et al. Reduced Salt Intake for Heart Failure: A Systematic Review. JAMA Intern Med. 2018 Dec 1;178(12):1693-1700. PubMed
  23. Yancy CW. Sodium Restriction in Heart Failure: Too Much Uncertainty-Do the Trials. JAMA Intern Med. 2018 Dec 1;178(12):1700-1701. PubMed
  24. He FJ, Campbell NRC, Ma Y, MacGregor GA, Cogswell ME, Cook NR. Errors in estimating usual sodium intake by the Kawasaki formula alter its relationship with mortality: implications for public health. Int J Epidemiol. 2018;47(6):1784-1795. PubMed
  25. Murthy K, Ondrey GJ, Malkani N, et al. THE EFFECTS OF HYPONATREMIA ON BONE DENSITY AND FRACTURES: A SYSTEMATIC REVIEW AND META-ANALYSIS. Endocr Pract. 2019;25(4):366-378. PubMed
  26. Messerli FH, Hofstetter L, Syrogiannouli L, et al. Sodium intake, life expectancy, and all-cause mortality. Eur Heart J 2021;42(21):2103-2112. PubMed
  27. Graudal NA, Hubeck-Graudal T, Jurgens G. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride. Cochrane Database Syst Rev 2020;12(12):CD004022. PubMed
  28. Giatti S, Santos RB, Aielo AN, et al. Association of sodium with obstructive sleep apnea. The ELSA-Brasil study. Ann Am Thorac Soc 2021;18(3):502-510. PubMed
  29. Nan X, Lu H, Wu J, et al. The interactive association between sodium intake, alcohol consumption and hypertension among elderly in northern China: a cross-sectional study. BMC Geriatr 2021;21(1):135. PubMed
  30. Kyozuka H, Fukusda T, Murata T, et al. Impact of preconception sodium intake on hypertensive disorders of pregnancy: The Japan Environment and Children's study. Pregnancy Hypertens 2021;23:66-72. PubMed
  31. Zhao L, Ogden CL, Yang Q, et al. Association of usual sodium intake with obesity among US children and adolescents, NHANES 2009-2016. Obesity (Silver Spring) 2021;29(3):587-594. PubMed
  32. Ma Y, He FJ, Sun Q, et al. 24-Hour urinary sodium and potassium excretion and cardiovascular risk. N Engl J Med 2022;386(3):252-263. PubMed
  33. Liu J, Yang X, Zhang P, et al. Association of urinary sodium excretion and left ventricular hypertrophy in people with type 2 diabetes mellitus: A cross-sectional study. Front Endocrinol (Lausanne) 2021;12:728493. PubMed
  34. Filippini T, Malavolti M, Whelton PK, Vinceti M. Sodium intake and risk of hypertension: A systematic review and dose-response meta-analysis of observational cohort studies. Curr Hypertens Rep 2022;24(5):133-144. PubMed
  35. Wang DD, Li Y, Nguyen XT, et al. Dietary sodium and potassium intake and risk of non-fatal cardiovascular diseases: The million veteran program. Nutrients 2022;14(5):1121. PubMed
  36. Kwak JH, Park CH, Eun CS, et al. The associations of dietary intake of high sodium and low zinc with gastric cancer mortality: A prospective cohort study in Korea. Nutr Cancer 2022;74(10):3501-3508. PubMed
  37. George S, Maiti R, Mishra BR, Jena M, Mohapatra D. Effect of regulated add-on sodium chloride intake on stabilization of serum lithium concentration in bipolar disorder: A randomized controlled trial. Bipolar Disord 2023;25(1):66-75. PubMed
  38. Zhou TL, Schütten MTJ, Kroon AA, et al. Urinary Sodium Excretion and Salt Intake Are Not Associated With Blood Pressure Variability in a White General Population. J Am Heart Assoc 2023;12(1):e026578. PubMed

See these in context on the Sodium monograph →

Vitamin B12 30 references
  1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  2. Hartman TJ, Woodson K, Stolzenberg-Solomon R, et al. Association of the B-vitamins pyridoxal 5'-phosphate (B6), B12, and folate with lung cancer risk in older men. Am J Epidemiol 2001;153:688-94.. DOI
  3. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  4. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673-81. PubMed
  5. Collin, S. M., Metcalfe, C., Refsum, H., Lewis, S. J., Zuccolo, L., Smith, G. D., Chen, L., Harris, R., Davis, M., Marsden, G., Johnston, C., Lane, J. A., Ebbing, M., Bonaa, K. H., Nygard, O., Ueland, P. M., Grau, M. V., Baron, J. A., Donovan, J. L., Nea
  6. Geissbuhler, P., Mermillod, B., and Rapin, C. H. Elevated serum vitamin B12 levels associated with CRP as a predictive factor of mortality in palliative care cancer patients: a prospective study over five years. J.Pain Symptom.Manage. 2000;20(2):93-103. PubMed
  7. Salles, N., Herrmann, F., Sakbani, K., Rapin, C. H., and Sieber, C. High vitamin B12 level: a strong predictor of mortality in elderly inpatients. J Am Geriatr.Soc 2005;53(5):917-918.
  8. Looker, H. C., Fagot-Campagna, A., Gunter, E. W., Pfeiffer, C. M., Sievers, M. L., Bennett, P. H., Nelson, R. G., Hanson, R. L., and Knowler, W. C. Homocysteine and vitamin B(12) concentrations and mortality rates in type 2 diabetes. Diabetes Metab Res R
  9. Uhl, W., Nolting, A., Golor, G., Rost, K. L., and Kovar, A. Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study. Clin Toxicol (Phila) 2006;44 Suppl 1:17-28. PubMed
  10. Borron, S. W., Baud, F. J., Barriot, P., Imbert, M., and Bismuth, C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg.Med 2007;49(6):794-801, 801. PubMed
  11. Borron, S. W., Baud, F. J., Megarbane, B., and Bismuth, C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg.Med 2007;25(5):551-558. PubMed
  12. Lewis, J. G. Gout, Steatorrhoea, and Megaloblastic Anaemia. Ann Rheum.Dis 1962;21(3):284-286. PubMed
  13. Tal, S., Shavit, Y., Stern, F., and Malnick, S. Association between vitamin B12 levels and mortality in hospitalized older adults. J Am Geriatr.Soc 2010;58(3):523-526. PubMed
  14. Baztan, J. J., Gavidia, J. J., Gomez-Pavon, J., Esteve, A., and Ruiperez, I. High vitamin B12 levels and in-hospital mortality. J Am Geriatr.Soc 2010;58(11):2237-2238. PubMed
  15. Omboni, E., Checchini, M., and Longoni, F. [Hypopotassemia and megaloblastic anemia. Presentation of a case]. Minerva Med 8-31-1987;78(16):1255-1257.
  16. Aalfs As, Scholvinck LH, Horvath B. Acneiform eruption in a 5-year old due to vitamin B12 supplementation. Eur J Dermatol 2013;23(5):726-7. PubMed
  17. Balta I, Ozuguz P. Vitamin B12-induced acneiform eruption. Cutan Ocul Toxicol 2014;33(2):94-5. PubMed
  18. Carman KB, Belgemen T, Yis U. Involuntary movements misdiagnosed as seizure during vitamin B12 treatment. Pediatr Emerg Care 2013;29(11):1223-4. PubMed
  19. Djuric V, Bogic M, Popadic AP, et al. Anaphylactic reaction to hydroxycobalamin with tolerance to cyanocobalamin. Ann Allergy Asthma Immunol 2012;108(3):207-8. PubMed
  20. Kartel O, Gulec M, Demirel F, et al. Vitamin B12 allergy and successful desensitization with cyanocobalamin: A case report. Allergol Immunopath (Madr) 2012;40(5):324-5.
  21. Patiroglu T, Unal E, Yildirim S. Infantile tremor syndrome associated with cobalamin therapy: A case report. Clin Neurol Neurosurg 2013;115(9):1903-5. PubMed
  22. Schulte S, Barkema LW, Kardaun SH. Long-lasting atypical acneiform eruption with prominent comedones induced by hydroxocobalamin (vitamin B12). J Dtsch Dermatol Ges 2014;12(6):502-3.
  23. Zanus C, Alberini E, Costa P, et al. Involuntary movements after correction of vitamin B12 deficiency: A video-case report. Epileptic Disord 2012;14(2):174-80. PubMed
  24. Fanidi A, Carreras-Torres R, Larose TL, et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019 Sep 15;145(6):1499-1503. PubMed
  25. Fujita Y, Mizukami T, Maya Y, et al. Vitamin B12 allergy manifesting as lymphomatoid contact dermatitis. Eur J Dermatol. 2020;30(3):304-305. PubMed
  26. Dépret F, Hoffmann C, Daoud L, et al. Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study. Crit Care. 2019;23(1):421. PubMed
  27. Khairan P, Sobue T, Eshak ES, et al. Association of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer: the Japan Public Health Center-based (JPHC) prospective study. BMC Cancer 2021;21(1):982. PubMed
  28. Evans J, Pandya A, Ding Y, Qunibi WY. Hydroxocobalamin-Induced Oxalate Nephropathy in a Patient With Smoke Inhalation. Kidney Int Rep 2021;6(8):2228-2231. PubMed
  29. Lacombe V, Chabrun F, Lacout C, et al. Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer. Sci Rep 2021;11(1):13361. PubMed
  30. Pegalajar-García MD, Cebolla-Verdugo M, Prados-Carmona Á, Llamas-Segura C, Navarro-Triviño FJ. Systemic allergic dermatitis to cobalt present in cyanocobalamin supplementation. Contact Dermatitis 2023;89(3):203-205. PubMed

See these in context on the Vitamin B12 monograph →

Caffeine 236 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  8. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  9. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  10. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  11. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  12. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  13. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  14. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  15. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed
  16. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  17. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. PubMed
  18. Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. PubMed
  19. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  20. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  21. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  22. Tobias JD. Caffeine in the treatment of apnea associated with respiratory syncytial virus infection in neonates and infants. South Med J 2000;93:297-304. DOI
  23. Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. PubMed
  24. Lloyd T, Johnson-Rollings N, Eggli DF, et al. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr 2000;19:256-61. PubMed
  25. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  26. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  27. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  28. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  29. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  30. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 1996:144:642-4. PubMed
  31. Avisar R, Avisar E, Weinberger D. Effect of coffee consumption on intraocular pressure. Ann Pharmacother 2002;36:992-5.. PubMed
  32. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. PubMed
  33. Horner NK, Lampe JW. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness. J Am Diet Assoc 2000;100:1368-80. PubMed
  34. Bracken MB, Triche EW, Belanger K, et al. Association of maternal caffeine consumption with decrements in fetal growth. Am J Epidemiol 2003;157:456-66.. PubMed
  35. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  36. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  37. Dreher HM. The effect of caffeine reduction on sleep quality and well-being in persons with HIV. J Psychosom Res 2003;54:191-8.. PubMed
  38. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  39. Schechter MD, Timmons GD. Objectively measured hyperactivity--II. Caffeine and amphetamine effects. J Clin Pharmacol 1985;25:276-80.. PubMed
  40. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI
  41. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  42. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  43. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  44. May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982;31:656-61. PubMed
  45. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. PubMed
  46. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  47. Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. DOI
  48. Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. PubMed
  49. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  50. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  51. Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. PubMed
  52. Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7.
  53. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
  54. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  55. Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. PubMed
  56. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004;176:1-29. PubMed
  57. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  58. Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. DOI
  59. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  60. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  61. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8. PubMed
  62. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  63. Shet, M. S., McPhaul, M., Fisher, C. W., Stallings, N. R., and Estabrook, R. W. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997;25(11):1298-1303.
  64. Staib, A. H., Stille, W., Dietlein, G., Shah, P. M., Harder, S., Mieke, S., and Beer, C. Interaction between quinolones and caffeine. Drugs 1987;34 Suppl 1:170-174. PubMed
  65. Stille, W., Harder, S., Mieke, S., Beer, C., Shah, P. M., Frech, K., and Staib, A. H. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J.Antimicrob.Chemother. 1987;20(5):729-734. PubMed
  66. Fuhr, U., Strobl, G., Manaut, F., Anders, E. M., Sorgel, F., Lopez-de-Brinas, E., Chu, D. T., Pernet, A. G., Mahr, G., Sanz, F., and . Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isof
  67. Kot, M. and Daniel, W. A. Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes. Pharmacol Rep. 2009;61(6):1216-1220. PubMed
  68. Gasior, M., Borowicz, K., Buszewicz, G., Kleinrok, Z., and Czuczwar, S. J. Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia 1996;37(3 PubMed
  69. Jankiewicz, K., Chroscinska-Krawczyk, M., Blaszczyk, B., and Czuczwar, S. J. [Caffeine and antiepileptic drugs: experimental and clinical data]. Przegl.Lek. 2007;64(11):965-967.
  70. Luszczki, J. J., Zuchora, M., Sawicka, K. M., Kozinska, J., and Czuczwar, S. J. Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures i
  71. Chroscinska-Krawczyk, M., Jargiello-Baszak, M., Walek, M., Tylus, B., and Czuczwar, S. J. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol.Rep. 2011;63(1):12-18. PubMed
  72. Vaz, J., Kulkarni, C., David, J., and Joseph, T. Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. Indian J.Exp.Biol. 1998;36(1):112-114.
  73. Gasior, M., Swiader, M., Przybylko, M., Borowicz, K., Turski, W. A., Kleinrok, Z., and Czuczwar, S. J. Felbamate demonstrates low propensity for interaction with methylxanthines and Ca2+ channel modulators against experimental seizures in mice. Eur.J Phar PubMed
  74. Balogh, A., Klinger, G., Henschel, L., Borner, A., Vollanth, R., and Kuhnz, W. Influence of ethinylestradiol-containing combination oral contraceptives with gestodene or levonorgestrel on caffeine elimination. Eur.J.Clin.Pharmacol. 1995;48(2):161-166. PubMed
  75. Mohiuddin, M., Azam, A. T., Amran, M. S., and Hossain, M. A. In vive effects of gliclazide and metformin on the plasma concentration of caffeine in healthy rats. Pak.J Biol Sci 5-1-2009;12(9):734-737.
  76. Mays, D. C., Camisa, C., Cheney, P., Pacula, C. M., Nawoot, S., and Gerber, N. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin.Pharmacol.Ther. 1987;42(6):621-626. PubMed
  77. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  78. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.
  79. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  80. Bailey, D. N., Weibert, R. T., Naylor, A. J., and Shaw, R. F. A study of salicylate and caffeine excretion in the breast milk of two nursing mothers. J.Anal.Toxicol. 1982;6(2):64-68. PubMed
  81. Griffiths, R. R. and Chausmer, A. L. Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Nihon Shinkei Seishin Yakurigaku Zasshi 2000;20(
  82. Karacan, I., Thornby, J. I., Anch, M., Booth, G. H., Williams, R. L., and Salis, P. J. Dose-related sleep disturbances induced by coffee and caffeine. Clin Pharmacol Ther 1976;20(6):682-689. PubMed
  83. Quirce, G. S., Freire, P., Fernandez, R. M., Davila, I., and Losada, E. Urticaria from caffeine. J.Allergy Clin Immunol. 1991;88(4):680-681. PubMed
  84. Hughes, J. R., Higgins, S. T., Bickel, W. K., Hunt, W. K., Fenwick, J. W., Gulliver, S. B., and Mireault, G. C. Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Arch.Gen.Psychiatry 1991;48(7):611-617. PubMed
  85. Adams, B. A. and Brubaker, R. F. Caffeine has no clinically significant effect on aqueous humor flow in the normal human eye. Ophthalmology 1990;97(8):1030-1031. PubMed
  86. Davis, R. H. Does caffeine ingestion affect intraocular pressure?. Ophthalmology 1989;96(11):1680-1681. PubMed
  87. Higginbotham, E. J., Kilimanjaro, H. A., Wilensky, J. T., Batenhorst, R. L., and Hermann, D. The effect of caffeine on intraocular pressure in glaucoma patients. Ophthalmology 1989;96(5):624-626.
  88. Wrenn, K. D. and Oschner, I. Rhabdomyolysis induced by a caffeine overdose. Ann.Emerg.Med. 1989;18(1):94-97. PubMed
  89. Pola, J., Subiza, J., Armentia, A., Zapata, C., Hinojosa, M., Losada, E., and Valdivieso, R. Urticaria caused by caffeine. Ann.Allergy 1988;60(3):207-208.
  90. Lane, J. D. and Williams, R. B., Jr. Cardiovascular effects of caffeine and stress in regular coffee drinkers. Psychophysiology 1987;24(2):157-164. PubMed
  91. Shirlow, M. J. and Mathers, C. D. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. Int.J.Epidemiol. 1985;14(2):239-248. PubMed
  92. Stillner, V., Popkin, M. K., and Pierce, C. M. Caffeine-induced delirium during prolonged competitive stress. Am.J.Psychiatry 1978;135(7):855-856. PubMed
  93. Levy, M. and Zylber-Katz, E. Caffeine metabolism and coffee-attributed sleep disturbances. Clin Pharmacol Ther 1983;33(6):770-775. PubMed
  94. Brown, S. L., Salive, M. E., Pahor, M., Foley, D. J., Corti, M. C., Langlois, J. A., Wallace, R. B., and Harris, T. B. Occult caffeine as a source of sleep problems in an older population. J.Am.Geriatr.Soc. 1995;43(8):860-864. PubMed
  95. Sung, B. H., Whitsett, T. L., Lovallo, W. R., al'Absi, M., Pincomb, G. A., and Wilson, M. F. Prolonged increase in blood pressure by a single oral dose of caffeine in mildly hypertensive men. Am.J Hypertens. 1994;7(8):755-758. PubMed
  96. Caballero, T., Garcia-Ara, C., Pascual, C., Diaz-Pena, J. M., and Ojeda, A. Urticaria induced by caffeine. J.Investig.Allergol.Clin Immunol. 1993;3(3):160-162.
  97. Smits, P., Temme, L., and Thien, T. The cardiovascular interaction between caffeine and nicotine in humans. Clin Pharmacol Ther 1993;54(2):194-204. PubMed
  98. Garrett, B. E. and Griffiths, R. R. Physical dependence increases the relative reinforcing effects of caffeine versus placebo. Psychopharmacology (Berl) 1998;139(3):195-202. PubMed
  99. Lane, J. D. and Phillips-Bute, B. G. Caffeine deprivation affects vigilance performance and mood. Physiol Behav. 1998;65(1):171-175. PubMed
  100. Boekema, P. J., Samsom, M., van Berge Henegouwen, G. P., and Smout, A. J. Coffee and gastrointestinal function: facts and fiction. A review. Scand J Gastroenterol.Suppl 1999;230:35-39. PubMed
  101. Terry, P., Lagergren, J., Wolk, A., and Nyren, O. Reflux-inducing dietary factors and risk of adenocarcinoma of the esophagus and gastric cardia. Nutr Cancer 2000;38(2):186-191.
  102. Pollak, C. P. and Bright, D. Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth-graders. Pediatrics 2003;111(1):42-46. PubMed
  103. DiBaise, J. K. A randomized, double-blind comparison of two different coffee-roasting processes on development of heartburn and dyspepsia in coffee-sensitive individuals. Dig.Dis.Sci 2003;48(4):652-656. PubMed
  104. Wang, J. H., Luo, J. Y., Dong, L., Gong, J., and Tong, M. Epidemiology of gastroesophageal reflux disease: a general population-based study in Xi'an of Northwest China. World J Gastroenterol. 6-1-2004;10(11):1647-1651. PubMed
  105. Naliboff, B. D., Mayer, M., Fass, R., Fitzgerald, L. Z., Chang, L., Bolus, R., and Mayer, E. A. The effect of life stress on symptoms of heartburn. Psychosom.Med 2004;66(3):426-434. PubMed
  106. Massey, L. K. and Sutton, R. A. Acute caffeine effects on urine composition and calcium kidney stone risk in calcium stone formers. J.Urol. 2004;172(2):555-558. PubMed
  107. Tavani, A. and La, Vecchia C. Coffee, decaffeinated coffee, tea and cancer of the colon and rectum: a review of epidemiological studies, 1990-2003. Cancer Causes Control 2004;15(8):743-757. PubMed
  108. Noordzij, M., Uiterwaal, C. S., Arends, L. R., Kok, F. J., Grobbee, D. E., and Geleijnse, J. M. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens. 2005;23(5):921-928. PubMed
  109. Chandrasekaran, S., Rochtchina, E., and Mitchell, P. Effects of caffeine on intraocular pressure: the Blue Mountains Eye Study. J Glaucoma. 2005;14(6):504-507. PubMed
  110. Morgan, J. C. and Sethi, K. D. Drug-induced tremors. Lancet Neurol. 2005;4(12):866-876. PubMed
  111. Doan, B. K., Hickey, P. A., Lieberman, H. R., and Fischer, J. R. Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Aviat.Space Environ Med 2006;77(10):1034-1040.
  112. Whalen, D. J., Silk, J. S., Semel, M., Forbes, E. E., Ryan, N. D., Axelson, D. A., Birmaher, B., and Dahl, R. E. Caffeine consumption, sleep, and affect in the natural environments of depressed youth and healthy controls. J Pediatr.Psychol. 2008;33(4):35 PubMed
  113. MacKenzie, T., Comi, R., Sluss, P., Keisari, R., Manwar, S., Kim, J., Larson, R., and Baron, J. A. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-1698. PubMed
  114. Mort, J. R. and Kruse, H. R. Timing of blood pressure measurement related to caffeine consumption. Ann Pharmacother. 2008;42(1):105-110.
  115. Ganmaa, D., Willett, W. C., Li, T. Y., Feskanich, D., van Dam, R. M., Lopez-Garcia, E., Hunter, D. J., and Holmes, M. D. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer 5-1-2008;122(9):2071-2076. PubMed
  116. Killgore, W. D., Rupp, T. L., Grugle, N. L., Reichardt, R. M., Lipizzi, E. L., and Balkin, T. J. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness. J Sleep Res 2008;17(3):3 PubMed
  117. Ozsungur, S., Brenner, D., and El-Sohemy, A. Fourteen well-described caffeine withdrawal symptoms factor into three clusters. Psychopharmacology (Berl) 2009;201(4):541-548. PubMed
  118. Ishitani, K., Lin, J., Manson, J. E., Buring, J. E., and Zhang, S. M. Caffeine consumption and the risk of breast cancer in a large prospective cohort of women. Arch Intern Med 10-13-2008;168(18):2022-2031. PubMed
  119. Tunnicliffe, J. M., Erdman, K. A., Reimer, R. A., Lun, V., and Shearer, J. Consumption of dietary caffeine and coffee in physically active populations: physiological interactions. Appl Physiol Nutr Metab 2008;33(6):1301-1310. PubMed
  120. Sin, C. W., Ho, J. S., and Chung, J. W. Systematic review on the effectiveness of caffeine abstinence on the quality of sleep. J Clin Nurs. 2009;18(1):13-21. PubMed
  121. Lopez-Garcia, E., Rodriguez-Artalejo, F., Rexrode, K. M., Logroscino, G., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of stroke in women. Circulation 3-3-2009;119(8):1116-1123. PubMed
  122. Zhang, W., Lopez-Garcia, E., Li, T. Y., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of cardiovascular diseases and all-cause mortality among men with type 2 diabetes. Diabetes Care 2009;32(6):1043-1045. PubMed
  123. Killgore, W. D., Kahn-Greene, E. T., Grugle, N. L., Killgore, D. B., and Balkin, T. J. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 2-1-2009;32(2):205-216. PubMed
  124. Natale, F., Cirillo, C., Di Marco, G. M., di Vetta, L. S., Aronne, L., Siciliano, A., Mocerino, R., Tedesco, M. A., Golino, P., and Calabro, R. When chewing gum is more than just a bad habit. Lancet 5-30-2009;373(9678):1918. PubMed
  125. Calamaro, C. J., Mason, T. B., and Ratcliffe, S. J. Adolescents living the 24/7 lifestyle: effects of caffeine and technology on sleep duration and daytime functioning. Pediatrics 2009;123(6):e1005-e1010. PubMed
  126. Koran, L. M., Aboujaoude, E., and Gamel, N. N. Double-blind study of dextroamphetamine versus caffeine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2009;70(11):1530-1535. PubMed
  127. Luebbe, A. M. and Bell, D. J. Mountain Dew or mountain don't?: a pilot investigation of caffeine use parameters and relations to depression and anxiety symptoms in 5th- and 10th-grade students. J Sch Health 2009;79(8):380-387.
  128. Skouroliakou, M., Bacopoulou, F., and Markantonis, S. L. Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial. J Paediatr.Child Health 2009;45(10):587-592. PubMed
  129. Urade, Y. [Molecular mechanisms of insomnia]. Nippon Rinsho 2009;67(8):1489-1493.
  130. Montandon, G., Horner, R. L., Kinkead, R., and Bairam, A. Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats. J Physiol 11-15-2009;587(Pt 22):5493-5507. PubMed
  131. Addicott, M. A. and Laurienti, P. J. A comparison of the effects of caffeine following abstinence and normal caffeine use. Psychopharmacology (Berl) 2009;207(3):423-431. PubMed
  132. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433. PubMed
  133. Moisey, L. L., Robinson, L. E., and Graham, T. E. Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males. Br.J Nutr. 2010;103(6):833-841. PubMed
  134. Chroscinska-Krawczyk, M., Ratnaraj, N., Patsalos, P. N., and Czuczwar, S. J. Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep. 2009;61(5):819 PubMed
  135. Attwood, A., Terry, P., and Higgs, S. Conditioned effects of caffeine on performance in humans. Physiol Behav 3-3-2010;99(3):286-293. PubMed
  136. Skinner, T. L., Jenkins, D. G., Coombes, J. S., Taaffe, D. R., and Leveritt, M. D. Dose response of caffeine on 2000-m rowing performance. Med Sci Sports Exerc. 2010;42(3):571-576. PubMed
  137. Holick, C. N., Smith, S. G., Giovannucci, E., and Michaud, D. S. Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies. Cancer Epidemiol.Biomarkers Prev 2010;19(1):39-47. PubMed
  138. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  139. Buscemi, S., Verga, S., Batsis, J. A., Donatelli, M., Tranchina, M. R., Belmonte, S., Mattina, A., Re, A., and Cerasola, G. Acute effects of coffee on endothelial function in healthy subjects. Eur.J Clin Nutr. 2010;64(5):483-489. PubMed
  140. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  141. Greenwood, D. C., Alwan, N., Boylan, S., Cade, J. E., Charvill, J., Chipps, K. C., Cooke, M. S., Dolby, V. A., Hay, A. W., Kassam, S., Kirk, S. F., Konje, J. C., Potdar, N., Shires, S., Simpson, N., Taub, N., Thomas, J. D., Walker, J., White, K. L., and
  142. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  143. Brick, C. A., Seely, D. L., and Palermo, T. M. Association between sleep hygiene and sleep quality in medical students. Behav Sleep Med 2010;8(2):113-121. PubMed
  144. Digdon, N. L. Circadian preference and college students' beliefs about sleep education. Chronobiol.Int 2010;27(2):297-317. PubMed
  145. Boos, C. J., White, S. H., Bland, S. A., and McAllister, P. D. Dietary supplements and military operations: caution is advised. J R.Army Med Corps 2010;156(1):41-43. PubMed
  146. Casiglia, E., Bongiovi, S., Paleari, C. D., Petucco, S., Boni, M., Colangeli, G., Penzo, M., and Pessina, A. C. Haemodynamic effects of coffee and caffeine in normal volunteers: a placebo-controlled clinical study. J.Intern.Med. 1991;229(6):501-504. PubMed
  147. Aguggia, M. and Saracco, M. G. Pathophysiology of migraine chronification. Neurol.Sci 2010;31 Suppl 1:S15-S17. PubMed
  148. Torelli, P. and Manzoni, G. C. Fasting headache. Curr Pain Headache Rep. 2010;14(4):284-291.
  149. Farag, N. H., Whitsett, T. L., McKey, B. S., Wilson, M. F., Vincent, A. S., Everson-Rose, S. A., and Lovallo, W. R. Caffeine and blood pressure response: sex, age, and hormonal status. J Womens Health (Larchmt.) 2010;19(6):1171-1176. PubMed
  150. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  151. Suen, L. K., Tam, W. W., and Hon, K. L. Association of sleep hygiene-related factors and sleep quality among university students in Hong Kong. Hong.Kong.Med.J 2010;16(3):180-185.
  152. Stafford, L. D., Wright, C., and Yeomans, M. R. The drink remains the same: implicit positive associations in high but not moderate or non-caffeine users. Psychol.Addict.Behav. 2010;24(2):274-281. PubMed
  153. Conen, D., Chiuve, S. E., Everett, B. M., Zhang, S. M., Buring, J. E., and Albert, C. M. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr 2010;92(3):509-514. PubMed
  154. Freire, R. C., Perna, G., and Nardi, A. E. Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment. Harv.Rev.Psychiatry 2010;18(4):220-229. PubMed
  155. Reis, J. P., Loria, C. M., Steffen, L. M., Zhou, X., van, Horn L., Siscovick, D. S., Jacobs, D. R., Jr., and Carr, J. J. Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study. A PubMed
  156. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  157. Kujawa-Hadrys, M., Tosik, D., and Bartel, H. Changes in thickness of each layer of developing chicken cornea after administration of caffeine. Folia Histochem.Cytobiol. 2010;48(2):273-277. PubMed
  158. Boggs, D. A., Palmer, J. R., Stampfer, M. J., Spiegelman, D., Adams-Campbell, L. L., and Rosenberg, L. Tea and coffee intake in relation to risk of breast cancer in the Black Women's Health Study. Cancer Causes Control 2010;21(11):1941-1948. PubMed
  159. Li, S., Zhu, S., Jin, X., Yan, C., Wu, S., Jiang, F., and Shen, X. Risk factors associated with short sleep duration among Chinese school-aged children. Sleep Med. 2010;11(9):907-916. PubMed
  160. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  161. Knight, J. M., Avery, E. F., Janssen, I., and Powell, L. H. Cortisol and depressive symptoms in a population-based cohort of midlife women. Psychosom.Med. 2010;72(9):855-861. PubMed
  162. Porkka-Heiskanen, T. Methylxanthines and sleep. Handb.Exp.Pharmacol 2011;(200):331-348. PubMed
  163. Mostofsky, E., Schlaug, G., Mukamal, K. J., Rosamond, W. D., and Mittleman, M. A. Coffee and acute ischemic stroke onset: the Stroke Onset Study. Neurology 11-2-2010;75(18):1583-1588. PubMed
  164. Orozco-Gregorio, H., Mota-Rojas, D., Bonilla-Jaime, H., Trujillo-Ortega, M. E., Becerril-Herrera, M., Hernandez-Gonzalez, R., and Villanueva-Garcia, D. Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia PubMed
  165. Li, G. Z., Zhang, N., Du, P., Yang, Y., Wu, S. L., Xiao, Y. X., Jin, R., Liu, L., Shen, H., and Dai, Y. Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms: a Chinese multi-center study. Chin Med
  166. Duvnjak-Zaknich, D. M., Dawson, B. T., Wallman, K. E., and Henry, G. Effect of caffeine on reactive agility time when fresh and fatigued. Med.Sci.Sports Exerc. 2011;43(8):1523-1530. PubMed
  167. Astorino, T. A., Martin, B. J., Schachtsiek, L., Wong, K., and Ng, K. Minimal effect of acute caffeine ingestion on intense resistance training performance. J Strength.Cond.Res 2011;25(6):1752-1758. PubMed
  168. Kivity, S., Ben Aharon, Y., Man, A., and Topilsky, M. The effect of caffeine on exercise-induced bronchoconstriction. Chest 1990;97(5):1083-1085. PubMed
  169. Lubin, F. and Ron, E. Consumption of methylxanthine-containing beverages and the risk of breast cancer. Cancer Lett. 1990;53(2-3):81-90. PubMed
  170. Smits, P., Lenders, J. W., and Thien, T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin.Pharmacol.Ther. 1990;48(4):410-418. PubMed
  171. Rossignol, A. M. and Bonnlander, H. Caffeine-containing beverages, total fluid consumption, and premenstrual syndrome. Am.J.Public Health 1990;80(9):1106-1110. PubMed
  172. Birkett, N. J. and Logan, A. G. Caffeine-containing beverages and the prevalence of hypertension. J Hypertens.Suppl 1988;6(4):S620-S622. PubMed
  173. Fraumeni, J. F., Jr., Scotto, J., and Dunham, L. J. Coffee-drinking and bladder cancer. Lancet 11-27-1971;2(7735):1204. PubMed
  174. Greden, J. F. Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry 1974;131(10):1089-1092. PubMed
  175. Whitsett, T. L., Manion, C. V., and Christensen, H. D. Cardiovascular effects of coffee and caffeine. Am.J.Cardiol. 3-15-1984;53(7):918-922. PubMed
  176. Firestone, P., Poitras-Wright, H., and Douglas, V. The effects of caffeine on hyperactive children. J.Learn.Disabil. 1978;11(3):133-141. PubMed
  177. Thomas, F. B., Steinbaugh, J. T., Fromkes, J. J., Mekhjian, H. S., and Caldwell, J. H. Inhibitory effect of coffee on lower esophageal sphincter pressure. Gastroenterology 1980;79(6):1262-1266. DOI
  178. Linn, S., Schoenbaum, S. C., Monson, R. R., Rosner, B., Stubblefield, P. G., and Ryan, K. J. No association between coffee consumption and adverse outcomes of pregnancy. N.Engl.J Med 1-21-1982;306(3):141-145. PubMed
  179. Cohen, S. Pathogenesis of coffee-induced gastrointestinal symptoms. N.Engl.J Med 7-17-1980;303(3):122-124. PubMed
  180. Feldman, M. and Barnett, C. Relationships between the acidity and osmolality of popular beverages and reported postprandial heartburn. Gastroenterology 1995;108(1):125-131. PubMed
  181. Quinlan, P., Lane, J., and Aspinall, L. Effects of hot tea, coffee and water ingestion on physiological responses and mood: the role of caffeine, water and beverage type. Psychopharmacology (Berl) 1997;134(2):164-173. PubMed
  182. Youngstedt, S. D., O'Connor, P. J., Crabbe, J. B., and Dishman, R. K. Acute exercise reduces caffeine-induced anxiogenesis. Med.Sci Sports Exerc. 1998;30(5):740-745. PubMed
  183. Kaminsky, L. A., Martin, C. A., and Whaley, M. H. Caffeine consumption habits do not influence the exercise blood pressure response following caffeine ingestion. J.Sports Med.Phys.Fitness 1998;38(1):53-58.
  184. McManamy, M. C. and Schube, P. G. Caffeine intoxication: report of a case the symptoms of which amounted to a psychosis. New England Journal of Medicine 1936;215:616-620. DOI
  185. Richter, J. E., Katz, P. O., and Waring, J. P. Gastroesophageal Reflux Disease. IFFGD 2000;
  186. Hsu, C., Harden, R. N., and Houle, T. Nicotine and caffeine intake in complex regional pain syndrome. Journal of Back and Musculoskeletal Rehabilitation 2002;16(1):33-38. PubMed
  187. Luebbe, A. M. Child and Adolescent Anxiety Sensitivity, Perceived Subjective Effects of Caffeine and Caffeine Consumption. J Caffeine Res 2011;1(4):213-218. DOI
  188. Li-Neng, Y., Greenstadt, L., and Shapiro, D. Effects of caffeine on blood pressure:A cross-cultural comparison. Psychophysiology 1983;20
  189. Fotherby, M. D., Ghandi, C., Haigh, R. A., Macdonald, T. A., and Potter, J. F. Sustained caffeine use has no pressor effect in the elderly. Cardiology in the Elderly 1994;2(6):499-503.
  190. Basurto Ona X, Uriona Tuma SM, Martínez García L, Solà I, Bonfill Cosp X. Drug therapy for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2013 28;2:CD001792. doi: 10.1002/14651858.CD001792.pub3. Review. PubMed
  191. Beaudoin MS, Allen B, Mazzetti G, Sullivan PJ, Graham TE. Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women. Appl Physiol Nutr Metab. 2013;38(2):140-7. doi: 10.1139/apnm-2012-0201. Epub 2012 9. PubMed
  192. Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J. Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart. 2013;99(19):1383-9. doi: 10.1136/heartjnl-2013-303950. Re PubMed
  193. Chen L, Bell EM, Browne ML, Druschel CM, Romitti PA, Schmidt RJ, Burns TL, Moslehi R, Olney RS; National Birth Defects Prevention Study. Maternal caffeine consumption and risk of congenital limb deficiencies. Birth Defects Res A Clin Mol Teratol. 2012 De PubMed
  194. Chen LW, Wu Y, Neelakantan N, Chong MF, Pan A, van Dam RM. Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis. BMC Med. 2014 19;12:174. doi: 10.1186/s12916-014-0174-6 PubMed
  195. Cheng M, Hu Z, Lu X, Huang J, Gu D. Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies. Can J Cardiol. 2014 Apr;30(4):448-54. doi: 10.1016/j.cjca.2013.12.026. Epub 2014 2. Review. PubMed
  196. Chiaffarino F, Bravi F, Cipriani S, Parazzini F, Ricci E, Viganò P, La Vecchia C. Coffee and caffeine intake and risk of endometriosis: a meta-analysis. Eur J Nutr. 2014 Oct;53(7):1573-9. doi: 10.1007/s00394-014-0662-7. Epub 2014 31. PubMed
  197. Greenwood DC, Thatcher NJ, Ye J, Garrard L, Keogh G, King LG, Cade JE. Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis. Eur J Epidemiol. 2014;29(10):725-34. doi: 10.1007/s10654-014-9944-x. PubMed
  198. Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies. Gynecol Oncol. 2013 Jun;129(3):620-9. doi: 10.1016/j.ygyno.2013.03.014. Epub 2013 25. Review. PubMed
  199. Lee SM, Choi NK, Lee BC, Cho KH, Yoon BW, Park BJ. Caffeine-containing medicines increase the risk of hemorrhagic stroke. Stroke. 2013 Aug;44(8):2139-43. doi: 10.1161/STROKEAHA.111.674077. Epub 2013 6. PubMed
  200. Sanikini H, Dik VK, Siersema PD, Bhoo-Pathy N, Uiterwaal CS, Peeters PH, González CA, Zamora-Ros R, Overvad K, Tjønneland A, Roswall N, Boutron-Ruault MC, Fagherazzi G, Racine A, Kühn T, Katzke V, Boeing H, Trichopoulou A, Trichopoulos D, Lagiou P, Palli
  201. Simonin C, Duru C, Salleron J, Hincker P, Charles P, Delval A, Youssov K, Burnouf S, Azulay JP, Verny C, Scherer C, Tranchant C, Goizet C, Debruxelles S, Defebvre L, Sablonnière B, Romon-Rousseaux M, Buée L, Destée A, Godefroy O, Dürr A, Landwehrmeyer B;
  202. Szpak A, Allen D. A case of acute suicidality following excessive caffeine intake. J Psychopharmacol. 2012 Nov;26(11):1502-10. doi: 10.1177/0269881112442788. Epub 2012 2. PubMed
  203. van der Hoeven N, Visser I, Schene A, van den Born BJ. Severe hypertension related to caffeinated coffee and tranylcypromine: a case report. Ann Intern Med. 2014 May 6;160(9):657-8. doi: 10.7326/L14-5009-8. No abstract available. PubMed
  204. Dixit S, Stein PK, Dewland TA, Dukes JW, Vittinghoff E, Heckbert SR, Marcus GM. Consumption of Caffeinated Products and Cardiac Ectopy. J Am Heart Assoc. 2016 26;5(1). pii: e002503. doi: 10.1161/JAHA.115.002503. PubMed
  205. Sheppard SG. A preliminary investigation of ibogaine: case reports and recommendations for further study. J Subst Abuse Treat. 1994 Jul-Aug;11(4):379-85. PubMed
  206. Zuchinali P, Riberio PA, Pimentel M, da Rosa PR, Zimerman LI, Rohde LE. Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies. Europace 2016 Feb;18(2):257-66. PubMed
  207. Rhee J, Kim R, Kim Y, et al. Maternal caffeine consumption during pregnancy and risk of low birth weight: a dose-response meta-analysis of observational studies. PLoS One. 2015 Jul 20;10(7):e0132334. PubMed
  208. Zuchinali P, Souza GC, Pimentel M, et al. Short-term effects of high-dose caffeine on cardiac arrhythmias in patients with heart failure: a randomized clinical trial. JAMA Intern Med. 2016 Dec 1;176(12):1752-59. PubMed
  209. Lystrup RM, Leggit JC. Caffeine toxicity due to supplement use in caffeine - naïve individual: a cautionary tale. Mil Med. 2015 Aug;180(8):e936-40. PubMed
  210. Magdalan J, Zawadzki M, Skowronek R, et al. Nonfatal and fata intoxications with pure caffeine - report of three different cases. Forensic Sci Med Pathol. 2017 Sep;13(3):355-58.
  211. Trexler ET, Smith-Ryan AE, Roelofs EJ, Hirsch KR, Persky AM, Mock AG. Effects of coffee and caffeine anhydrous intake during creatine loading. J Strength Cond Res. 2016 May;30(5):1438-46. PubMed
  212. Lagier D, Nee L, Guieu R, et al. Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: a randomized controlled clinical trial. Eur J Anaesthesiol. 2018 Apr 26. [Epub ahead of DOI
  213. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  214. Wang HR, Woo YS, Bahk WM. Caffeine-induced psychiatric manifestations: a review. Int Clin Psychopharmacol. 2015 Jul;30(4):179-82. PubMed
  215. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648. PubMed
  216. Vliegenthart R, Miedema M, Hutten GJ, van Kaam AH, Onland W. High versus standard dose caffeine for apnoea: a systematic review. Arch Dis Child Fetal Neonatal Ed 2018;103(6):F523-9. doi: 10.1136/archdischild-2017-313556. PubMed
  217. Modzelewska D, Bellocco R, Elfvin A, et al. Caffeine exposure during pregnancy, small for gestational age birth and neonatal outcome - results from the Norwegian Mother and Child Cohort Study. BMC Pregnancy Childbirth. 2019;19(1):80. PubMed
  218. Shen JG, Brooks MB, Cincotta J, Manjourides JD. Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: A systematic review and meta-analysis. J Sci Med Sport. 2019;22(2):232-238. PubMed
  219. Berglundh S, Vollrath M, Brants&aelig;ter 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 →

Vinpocetine 27 references
  1. Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol 1991;6:31-43. PubMed
  2. Balestreri R, Fontana L, Astengo F. A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. J Am Geriatr Soc 1987;35:425-30. PubMed
  3. Akopov SE, Gabrielian ES. Effects of aspirin, dipyridamole, nifedipine and cavinton which act on platelet aggregation induced by different aggregating agents alone and in combination. Eur J Clin Pharmacol 1992;42:257-9. PubMed
  4. Kidd PM. A review of nutrients and botanicals in the integrative management of cognitive dysfunction. Altern Med Rev 1999;4:144-61..
  5. Wollschlaeger B. Efficacy of vinpocetine in the management of cognitive impairment and memory loss. JANA 2001;4:25-30.
  6. Hitzenberger G, Sommer W, Grandt R. Influence of vinpocetine on warfarin-induced inhibition of coagulation. Int J Clin Pharmacol Ther Toxicol 1990;28:323-8..
  7. Dekoninck, W. J., Jocquet, P., Jacquy, J., and Henriet, M. Comparative study of the clinical effects of vincamine + glycerol versus glycerol + placebo in the acute phase of stroke. Arzneimittelforschung. 1978;28(9):1654-1657.
  8. Fischhof, P. K., Moslinger-Gehmayr, R., Herrmann, W. M., Friedmann, A., and Russmann, D. L. Therapeutic efficacy of vincamine in dementia. Neuropsychobiology 1996;34(1):29-35. PubMed
  9. Feher, G., Koltai, K., Kesmarky, G., Horvath, B., Toth, K., Komoly, S., and Szapary, L. Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases. Phytomedicine. 2009;16(2-3):111-117. PubMed
  10. Kuzuya, F. Effects of vinpocetine on platelet aggregability and erythrocyte deformability. Ther Hung. 1985;33(1):22-34.
  11. Kovacs, L. Cavinton in the treatment of acute stroke. Ther Hung. 1985;33(1):50-57.
  12. Osawa, M. and Maruyama, S. Effects of TCV-3B (vinpocetine) on blood viscosity in ischemic cerebrovascular diseases. Ther.Hung. 1985;33(1):7-12.
  13. Ebi, O. Open-labeled phase III clinical trials with vinpocetine in Japan. Ther.Hung. 1985;33(1):41-49.
  14. Richichi, I., Valsecchi, O., Falcone, C., Sofi, A., and Zanini, L. [A case of "torsade de pointe" during vincamine therapy]. Minerva Cardioangiol. 1978;26(3):197-200.
  15. Dany, F., Merle, L., Goudoud, J. C., Liozon, F., Blanc, P., Bouvot, J. C., Nicot, G., and Dangoumau, J. [Cardiac toxicity of vincamine: a seven cases report of ventricular arrhythmias by parenteral administration of vincamine (author's transl)]. Therapie
  16. Fenzl, E., Apecechea, M., Schaltenbr, R., and Fridel, R. Long term study concerning tolerance and efficacy of vinpocetine in elderly patients suffering from a mild to moderate organic psychosyndrome. Senile dementia: early detection 1986;580-585.
  17. Peruzza, M. and DeJacobis, M. A double-blind placebo controlled evaluation of the efficacy and safety of vinpocetine in the treatment of patients with chronic vascular or degenerative senile cerebral dysfunction. ADV THER 1986;3(4):201-209.
  18. Manconi, E., Binaghi, F., and Pitzus, F. A double-blind clinical trial of vinpocetine in the treatment of cerebral insufficiency of vascular and degenerative origin. CURR THER RES, CLIN EXP 1986;40(4):702-709.
  19. Blaha, L., Erzigkeit, H. L., Adamczyk, L. A., Freytag, L. S., and Schaltenbrand, R. Clinical evidence of the effectiveness of vinpocetine in the treatment of organic psychosyndrome. Human Psychopharmacology: Clinical & Experimental 1989;4(2):103-111. DOI
  20. Shimizu, Y., Saitoh, K., Nakayama, M., Suto, K., Daikohara, R., and Nemoto, T. Agranulocytosis induced by vinpocetine. Medicine On-line 2011;
  21. Kong L, Song C, Ye L, et al. The Effect of Vinpocetine on Human Cytochrome P450 Isoenzymes by Using a Cocktail Method. Evid Based Complement Alternat Med. 2016;2016:5017135. PubMed
  22. Vinpocetine in Dietary Supplements. FDA Food/Dietary Supplements/Products & Ingredients. Available at: http://www.fda.gov/Food/DietarySupplements/ProductsIngredients/ucm518478.htm. Accessed 6 September 2016.
  23. Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine. FDA Food/Dietary Supplements/Products & Ingredients. Available at: https://www.fda.gov/news-events/press-announcements/statement-
  24. Zhang W, Huang Y, Li Y, et al. Efficacy and safety of vinpocetine as part of treatment for acute cerebral infarction: A randomized, open-label, controlled, multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) trial. Clin Drug Investig 2016; PubMed
  25. National Toxicology Program. NTP technical report on the prenatal development toxicity studies of vinpocetine (CAS No. 42971-09-5) in Sprague Dawley Rats and New Zealand White Rabbits (Gavage Studies). Research Triangle Park, NC: National Toxicology Progr
  26. Gutiérrez-Farfán I, Reyes-Legorreta C, Solís-Olguín M, Alatorre-Miguel E, Verduzco-Mendoza A, Durand-Rivera A. Evaluation of vinpocetine as a therapy in patients with sensorineural hearing loss: a phase II, open-label, single-center study. J Pharmacol Sci PubMed
  27. Hu X, Guo K, Li J, et al. Postoperative ecchymoma of eyelid after botulinum toxin injection for hemifacial spasm: a case report. Front Neurol 2023;14:1171303. PubMed

See these in context on the Vinpocetine monograph →

Acai 2 references
  1. Udani JK, Singh BB, Singh VJ, Barrett ML. Effects of acai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: a pilot study. Nutr J 2011;10:45.
  2. de Liz S, Cardoso AL, Copetti CLK, et al. Açaí (Euterpe oleracea Mart.) and juçara (Euterpe edulis Mart.) juices improved HDL-c levels and antioxidant defense of healthy adults in a 4-week randomized cross-over study. Clin Nutr. 2020;39(12):3629-3636. PubMed

See these in context on the Acai monograph →

Pomegranate 27 references
  1. Igea JM, Cuesta J, Cuevas M, et al. Adverse reaction to pomegranate ingestion. Allergy 1991;46:472-4. DOI
  2. Gaig P, Bartolome B, Lleonart R, et al. Allergy to pomegranate (Punica granatum). Allergy 1999;54:287-8.
  3. Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis 2001;158:195-8. PubMed
  4. Valsecchi R, Reseghetti A, Leghissa P, et al. Immediate contact hypersensitivity to pomegranate. Contact Dermatitis 1998;38:44-5. PubMed
  5. Esmaillzadeh A, Tahbaz F, Gaieni I, et al. Concentrated pomegranate juice improves lipid profiles in diabetic patients with hyperlipidemia. J Med Food 2004;7:305-8. PubMed
  6. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr 2004;23:423-33. DOI
  7. Hidaka M, Okumura M, Fujita K, et al. Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metab Dispos 2005;33:644-8. PubMed
  8. Loren DJ, Seeram NP, Schulman RN, Holtzman DM. Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury. Pediatr Res 2005;57:858-64. PubMed
  9. Kim ND, Mehta R, Yu W, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat 2002;71:203-17. PubMed
  10. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol 2006;98:705-6. PubMed
  11. Farkas D, Oleson LE, Zhao Y, et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol 2007;47:286-94. PubMed
  12. Yeo C, Shon J, Liu K, et al. The effects of pomegranate juice on the pharmacokinetics of simvastatin in healthy Korean subjects (PI-63). Clin Pharmacol Ther 2006;79:23.
  13. Farkas D, Greenblatt DJ. Influence of fruit juices on drug disposition: discrepancies between in vitro and clinical studies. Expert Opin Drug Metab Toxicol 2008;4:381-93.
  14. Nagata M, Hidaka M, Sekiya H, et al. Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats. Drug Metab Dispos 2007;35:302-5. PubMed
  15. Komperda KE. Potential interaction between pomegranate juice and warfarin. Pharmacotherapy 2009;29:1002-6. PubMed
  16. Gangemi S, Mistrello G, Roncarolo D, et al. Pomegranate-dependent exercise-induced anaphylaxis. J Investig Allergol Clin Immunol 2008;18:491-2.
  17. Misaka S, Nakamura R, Uchida S, et al. Effect of 2 weeks' consumption of pomegranate juice on the pharmacokinetics of a single dose of midazolam: an open-label, randomized, single-center, 2-period crossover study in healthy Japanese volunteers. Clin Ther PubMed
  18. Jarvis S, Li C, Bogle RG. Possible interaction between pomegranate juice and warfarin. Emerg Med J 2010;27:74-5. PubMed
  19. Esmaillzadeh, A., Tahbaz, F., Gaieni, I., Alavi-Majd, H., and Azadbakht, L. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. Int J Vitam.Nutr Res 2006;76(3):147-151. PubMed
  20. Forest, C. P., Padma-Nathan, H., and Liker, H. R. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study PubMed
  21. Wright, H. and Pipkin F. B. Pomegranates (Punica granatum), kiwifruit (Actinidia deliciosa) and blood pressure: a pilot study. Proceedings of the Nutrition Society 2008;67(8):1.
  22. Sohrab G, Sotoodeh G, Siasi F, et al. Effect of pomegranate juice consumption on blood pressure in type 2 diabetic patients. Iranian Journal of Endocrinology and Metabolism 2008;9:399-405, 470.
  23. Enrique E, Utz M, De Mateo JA, et al. Allergy to lipid transfer proteins: cross-reactivity among pomegranate, hazelnut, and peanut. Ann Allergy Asthma Immunol 2006;96(1):122-3. PubMed
  24. Hanley MJ, Masse G, Harmatz JS, et al. Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: divergence from in vitro results. Clin Pharmacol Ther 2012;92(5):651-7. PubMed
  25. Paller CJ, Ye X, Wozniak PJ, et al. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis 2013;16(1):50-5. PubMed
  26. Park SJ, Yeo CW, Shim EJ, et al. Pomegranate juice does not affect the disposition of simvastatin in healthy subjects. Eur J Drug Metab Pharmacokinet 2016;41(4):339-44. PubMed
  27. Ross MM, Cherkerzian S, Mikulis ND, et al. A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR. Sci Rep. 2021;11(1):3569. PubMed

See these in context on the Pomegranate monograph →

Cowhage 12 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  3. Anon. Epidemiological notes and reports: Mucuna pruriens-associated pruritus--New Jersey. MMWR Morb Mortal Wkly Rep 1985;34:732-3.
  4. HP-200 in Parkinson's Disease study group. An alternative medicine treatment for Parkinson's disease: Results of a multicenter clinical trial. J Alt Comp Med 1995;1:249-55. DOI
  5. Infante ME, Perez AM, Simao MR, et al. Outbreak of acute toxic psychosis attributed to Mucuna pruriens. Lancet 1990;336:1129. PubMed
  6. Vaidya AB, Rajagopalan TG, Mankodi NA, et al. Treatment of Parkinson's disease with the cowhage plant-Mucuna pruriens Bak. Neurol India 1978;26:171-6.
  7. Vadivel V, Janardhanan K. Nutritional and anti-nutritional composition of velvet bean: an under-utilized food legume in south India. Int J Food Sci Nutr 2000;51:279-87. PubMed
  8. Akhtar MS, Qureshi AQ, Iqbal J. Antidiabetic evaluation of Mucuna pruriens, Linn seeds. J Pak Med Assoc 1990;40:147-50.
  9. Prakash, D., Niranjan, A., and Tewari, S. K. Some nutritional properties of the seeds of three Mucuna species. Int.J.Food Sci.Nutr. 2001;52(1):79-82.
  10. Vadivel, V. and Janardhanan, K. Nutritional and antinutritional characteristics of seven South Indian wild legumes. Plant Foods Hum.Nutr 2005;60(2):69-75. PubMed
  11. Creapure (Creatine Monohydrate). Toxicological Datasheet. Degussa BioActives. Available at: https://www.fda.gov/ohrms/DOCKETS/.../95s-0316-rpt0154-54-Ref-50-vol112.pdf.
  12. Pulikkalpura H, Kurup R, Mathew PJ, Baby S. Levodopa in Mucuna pruriens and its degradation. Sci Rep 2015;5:11078. PubMed

See these in context on the Cowhage monograph →

Adenosine 10 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Agteresch HJ, Dagnelie PC, van den Berg JW, Wilson JH. Adenosine triphosphate: established and potential clinical applications. Drugs 1999;58:211-32.. PubMed
  3. Agteresch HJ, Dagnelie PC, van der Gaast A, et al. Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer. J Natl Cancer Inst 2000;92:321-8.. PubMed
  4. Haskell CM, Wong M, Williams A, Lee LY. Phase I trial of extracellular adenosine 5'-triphosphate in patients with advanced cancer. Med Pediatr Oncol 1996;27:165-73.. DOI
  5. Haskell CM, Mendoza E, Pisters KM, et al. Phase II study of intravenous adenosine 5'-triphosphate in patients with previously untreated stage IIIB and stage IV non-small cell lung cancer. Invest New Drugs 1998;16:81-5.. PubMed
  6. Eisenach JC, Curry R, Hood DD. Dose response of intrathecal adenosine in experimental pain and allodynia. Anesthesiology 2002;97:938-42.. PubMed
  7. Agteresch HJ, Dagnelie PC, Rietveld T, et al. Pharmacokinetics of intravenous ATP in cancer patients. Eur J Clin Pharmacol 2000;56:49-55.. PubMed
  8. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  9. Litmann L, Anderson JD, Monroe MH. Adenosine and Aggrenox: A hazardous combination. Ann Intern Med 2002;137:E-76. PubMed
  10. Faghihi G, Iraji F, Rajaee Harandi M, et al. Comparison of the efficacy of topical minoxidil 5% and adenosine 0.75% solutions on male androgenic alopecia and measuring patient satisfaction rate. Acta Dermatovenerol Croat 2013;21(3):155-9.

See these in context on the Adenosine monograph →

Huperzine A 13 references
  1. Skolnick AA. Old Chinese herbal medicine used for fever yields possible new Alzheimer Disease therapy. JAMA 1997;277:776. DOI
  2. Ye JW, Cai JX, Wang LM, Tang XC. Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment. J Pharmacol Exp Ther 1999;288:814-9.. DOI
  3. Wang T, Tang XC. Reversal of scopolamine-induced deficits in radial maze performance by (-)-huperzine A: comparison with E2020 and tacrine. Eur J Pharmacol 1998;349:137-42. PubMed
  4. Xu SS, Gao ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao 1995;16:391-5.
  5. Zhang RW, Tang XC, Han YY, et al. [Drug evaluation of huperzine A in the treatment of senile memory disorders]. Chung Kuo Yao Li Hsueh Pao 1991;12:250-2.
  6. Xu SS, Cai ZY, Qu ZW, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao 1999;20:486-90.
  7. Felgenhauer N, Zilker T, Worek F, Eyer P. Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss. J Toxicol Clin Toxicol 2000;38:803-8.. PubMed
  8. Zhang, Z., Wang, X., Chen, Q., Shu, L., Wang, J., and Shan, G. [Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial]. Zhonghua Yi Xue Za Zhi 7-25-2002;82
  9. Cheng, D. H., Ren, H., and Tang, X. C. Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport 12-20-1996;8(1):97-101. PubMed
  10. Wang BS, Wang H, Wei ZH, Song YY, Zhang L, Chen HZ. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis. J Neural Transm (Vienna) 2009;116(4):457-65. PubMed
  11. Xu ZQ, Liang XM, Juan-Wu, Zhang YF, Zhu CX, Jiang XJ. Treatment with Huperzine A improves cognition in vascular dementia patients. Cell Biochem Biophys 2012;62(1):55-8. PubMed
  12. Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One 2013;8(9):e74916. PubMed
  13. Xing SH, Zhu CX, Zhang R, An L. Huperzine a in the treatment of Alzheimer's disease and vascular dementia: a meta-analysis. Evid Based Complement Alternat Med 2014;2014:363985. PubMed

See these in context on the Huperzine A monograph →

Bacopa 12 references
  1. Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology 2001;156:481-4..
  2. Yadav SK, Jain AK, Tripathi SN, Gupta JP. Irritable bowel syndrome: therapeutic evaluation of indigenous drugs. Indian J Med Res 1989;90:496-503..
  3. Morgan A, Stevens J. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med 2010;16:753-9.
  4. Kar, A., Panda, S., and Bharti, S. Relative efficacy of three medicinal plant extracts in the alteration of thyroid hormone concentrations in male mice. J Ethnopharmacol. 2002;81(2):281-285. PubMed
  5. Mukherjee, G. D. and Dey, C. D. Clinical trial on Brahmi. I. J.Exp.Med.Sci. 1966;10(1):5-11.
  6. Kar A, Pandit S, Mukherjee K, Bahadur S, Mukherjee PK. Safety assessment of selected medicinal food plants used in Ayurveda through CYP450 enzyme inhibition study. J Sci Food Agric 2017;97(1):333-40. doi: 10.1002/jsfa.7739. PubMed
  7. Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, et al. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol 2014;151(1):528-35. PubMed
  8. Ramasamy S, Kiew LV, Chung LY. Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents. Molecules 2014;19(2):2588-601. PubMed
  9. Prabhakar S, Vishnu VY, Modi M, et al. Efficacy of Bacopa monnieri (Brahmi) and donepezil in Alzheimer's disease and mild cognitive impairment: a randomized double-blind parallel phase 2b study. Ann Indian Acad Neurol 2020;23(6):767-73. PubMed
  10. Acquarulo B, Tandon P, Macica CM. Suspected cholinergic toxicity due to cevimeline hydrochloride and Bacopa monnieri interaction: a case report. J Med Case Rep 2022;16(1):253. PubMed
  11. Keegan AP, Stough C, Paris D, et al. Bacopa monnieri supplementation has no effect on serum brain-derived neurotrophic factor levels but beneficially modulates nuclear factor kappa B and cyclic AMP response element-binding protein levels in healthy elderl
  12. Yaworski AM, Blyumin M, Chang T, Mammen AL, Greene M. Necrotizing myopathy with elevated anti-HMGCR antibodies following exposure to the supplement Bacopa. Muscle Nerve 2023;67(2):E1-E3.

See these in context on the Bacopa monograph →

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

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