Major interaction on record — check this product against your medications before combining. Check your meds →
Dietary supplement

Brain Ingredients & Drug Interactions

by iwi

Softgel Capsule Category: Botanical With Nutrients
Most serious interaction: Major
The interaction bottom line Most serious interaction: Major

Brain is a dietary supplement by iwi with 6 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 957 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Coffee bean extract, Algae Oil, Chlorophyll. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Brain by iwi

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

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 11 of its 11 active ingredients.
  • “Omega-3 Fatty Acids” is listed as a grouped ingredient — the label gives one combined amount (358 mg) without saying how much of each component you get.
  • “Algae Oil” is listed as a grouped ingredient — the label gives one combined amount (950 mg) without saying how much of each component you get.
  • “Total Omega Fatty Acids” is listed as a grouped ingredient — the label gives one combined amount (391 mg) without saying how much of each component you get.

iwi Brain is a softgel with 11 ingredients, most of them fatty acids sourced from algae. The active components include omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid), omega-6 and omega-9 fatty acids, omega-7 fatty acids, and polar lipids — all from the algae oil base.

It also contains phosphatidylserine (a phospholipid that may support brain function), chlorophyll, vitamin B6, and green coffee bean extract (which contains caffeine). The inactive ingredients are the softgel shell itself and other excipients.

Does it work?

Moderate 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
Moderate

Some clinical evidence supports this product's ingredients for its stated purpose, but it isn't conclusive.

Why this rating?
  • The label markets this product for: cognitive benefits and brain health.
  • We looked for evidence on: Age-related cognitive decline, Alzheimer disease, Attention deficit-hyperactivity disorder (ADHD), Cognitive function, Dementia, Memory — and 3 related terms.
  • The strongest evidence on file: Phosphatidylserine is rated "Possibly Effective" for Age-related cognitive decline (Natural Medicines).
  • Also on file: Phosphatidylserine is rated "Possibly Effective" for Alzheimer disease.
  • Also on file: Vitamin B6 is rated "Possibly Ineffective" for Age-related cognitive decline, Alzheimer disease.

The evidence for these ingredients is mixed. Phosphatidylserine is possibly effective for age-related cognitive decline and Alzheimer disease.

Green coffee bean extract is likely effective for mental alertness and possibly effective for Parkinson disease, heart failure, diabetes, and overall mortality. Omega-6 fatty acids, however, are rated possibly ineffective for high cholesterol, heart disease, and several other conditions.

The evidence for chlorophyll's effectiveness is not established — it's rated insufficient for wound healing, herpes, shingles, and skin cancer. Omega-3 and omega-9 fatty acids, omega-7, and phosphatidylserine's effects on cognitive function or ADHD remain insufficiently studied in our data.

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

Vitamin B6 is well tolerated at normal dietary amounts and standard supplement doses, but high doses over time can cause nerve damage (sensory neuropathy), particularly at intakes above 1,000 mg daily. Common side effects at any dose include headache, nausea, abdominal pain, and vomiting.

Chlorophyll is generally well tolerated in short-term use, though thorough safety data are limited. It can cause photosensitization (sun sensitivity) and rarely pseudoporphyria (blistering) with oral intake.

Phosphatidylserine is generally well tolerated, with occasional reports of flatulence, nausea, headache, and insomnia (more likely at higher doses). Green coffee bean extract — as a caffeine source — is well tolerated in moderate amounts but can cause agitation, anxiety, insomnia, chest pain, and heart palpitations, especially at higher intakes.

Omega-6 fatty acids from diet are fine, but supplement safety is not well established, and a high ratio of omega-6 to omega-3 in the diet may increase cardiovascular risk.

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

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

Why this rating?
  • 4 of the 5 matched ingredients can interact with medications — Chlorophyll, Vitamin B6, Coffee, Phosphatidylserine.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications; lithium; Parkinson's medications.
  • For scale: 957 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 iwi Brain, check with your pharmacist or doctor if you take ephedrine (Major risk with the caffeine in green coffee bean extract — avoid combining them). Also double-check if you're on blood pressure medications, seizure drugs (phenobarbital, phenytoin), amiodarone, methotrexate, anticholinergic or cholinergic drugs, or any of these medications: cimetidine, disulfiram, dipyridamole, clozapine, lamotrigine, pentobarbital, fluvoxamine, or levodopa (without carbidopa).

No interactions are documented for the other fatty acids in the product.

Check your own medication Run your meds through the checker above

The bottom line

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

iwi Brain may appeal to someone looking for algae-based omega fatty acids and brain-support ingredients like phosphatidylserine. However, if you take any prescription medication — especially blood pressure drugs, seizure medications, heart rhythm drugs, psychiatric medications, or lamotrigine — you need to check your specific list with our tool before starting, because the green coffee bean extract and vitamin B6 in this product can interact significantly.

Talk to your pharmacist about whether this product fits your regimen.

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

Assessment coverage: 5 of 11 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated May 22, 2021.

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 Brain, straight from the product label.

Brand iwi
Net contents 60 Softgel(s)
Market status On market
Date entered into DSLD May 22, 2021
DSLD ID 247653
Product type Botanical With Nutrients
Supplement form Softgel Capsule
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Vegan, Vegetarian, Adult (18 - 50 Years), Gluten Free, Dairy Free, Sugar 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 Brain by iwi, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Softgel(s)
Maximum serving Sizes:
2 Softgel(s)
Servings per container
30
IngredientAmount% DV
Calories5 Calorie(s)--
Omega-3 Fatty Acids358 mg--
Eicosapentaenoic Acid50 mg--
Vitamin B625 mg1470%
Docosahexaenoic Acid300 mg--
Cholesterol7 mg2%
Total Fat1 Gram(s)1%
Chlorophyll3 mg--
Omega-6 Fatty Acids10 mg--
Omega-9 Fatty Acids5 mg--
Other Omega-3 Fatty Acids8 mg--
Algae Oil950 mg--
Total Omega Fatty Acids391 mg--
Omega-7 Fatty Acids18 mg--
Polar Lipids30 mg--
Phosphatidylserine50 mg--
Green Coffee bean extract25 mg--

Other ingredients: Softgel Shell, Excipients

Tap any ingredient to jump to its full detail below.

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

Better living begins within

Not only do we avoid harming the ocean and the life in it, we also give back 1% of our net sales to Ocean Unite. iwi is good for every living thing. Learn more at: iwilife.com Oceanunite.org

Recyclable Made from recycled bottles

Focus Memory Mood Performance

Ocean Unite

Formula

iwi's patented Almega PL is the world's only source of Omega-3 that has 50% better absorption than fish or krill oil and offers huge cognitive benefits.

Omega-3 + PS and Green Coffee Bean

Seals/Symbols

Non GMO Certified by NSF

Formulation

Non GMO Certified by NSF Gluten free

Vegan

50% more absorption Sustainably sourced plant-based Made from algae

Contains no: sugar, gelatin, nuts, wheat, yeast, pollen, dairy, hidden additives or artificial flavors or colors.

Sustainably farmed in the USA, iwi algae is cultivated in the desert with saltwater and powered by the sun.

FDA Statement of Identity

Dietary Supplement

Suggested/Recommended/Usage/Directions

Directions: Take 2 softgels daily.

Precautions

Keep out of the reach of children.

Do not use if safety seal is broken or missing.

Storage

Store in a cool, dry place.

FDA Disclaimer Statement

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

See for yourself

Brain by iwi label

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

What’s inside

The Ingredients in Brain by iwi

These are the 6 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Softgel(s) Dosage formSoftgel Capsule Servings per container30 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.

Vitamin B6

Interacts with
210 drugs
25 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

Chlorophyll

Interacts with
337 drugs
3 mg per serving

Chlorophyll is the green pigment found in plants and algae, and supplements often use a stable form called chlorophyllin. It is most studied for reduc...

Chlorophyll monograph & interactions

Algae Oil

Interacts with
375 drugs
950 mg per serving

Algal oil is a plant-based source of the omega-3 fats DHA and (in some products) EPA, making it a popular alternative to fish oil for vegetarians, veg...

Algae Oil monograph & interactions
  • › Omega-6 Fatty Acids
  • › Omega-9 Fatty Acids
  • › Total Omega Fatty Acids
  • › Omega-7 Fatty Acids

Polar Lipids

30 mg per serving

Phosphatidylserine

Interacts with
219 drugs
50 mg per serving Form: Sunflower Lecithin

Phosphatidylserine is a natural fat-like compound found in cell membranes, especially in the brain, and it is sold mainly to support memory and thinki...

Phosphatidylserine monograph & interactions

Green Coffee bean extract

Interacts with
591 drugs
25 mg per serving Form: Chlorogenic Acid

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

Green Coffee bean extract monograph & interactions

Other (inactive) ingredients: Softgel Shell, Excipients. These complete the product’s ingredient list but are not active constituents.

Interaction report

Brain by iwi Drug Interactions

Want to check YOUR meds against Brain?

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
957Drugs
8 Major 937 Moderate 12 Minor

Ingredients driving the most interactions

Algae Oil 375

Each ingredient & the kinds of drugs it affects

For each ingredient in Brain with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Green Coffee bean extract33 drug types · 591 drugs

Ephedrine

Theoretically, concomitant use might increase the risk of stimulant adverse effects.
Coffee contains caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death. Tell patients to avoid taking caffeine with ephedrine and other stimulants.

Likelihood Probable Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Alendronate (Fosamax)

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

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

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

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

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

Likelihood Probable Evidence D
Cimetidine (Tagamet)

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

Likelihood Likely Evidence B
Clozapine (Clozaril)

Theoretically, coffee might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Coffee contains caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine.

Likelihood Possible Evidence B
Contraceptive Drugs

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in coffee.
Coffee contains caffeine. Oral contraceptive drugs can decrease caffeine clearance by 40% to 65%.

Likelihood Probable Evidence B
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, concomitant use might increase the risk of hypokalemia.
Coffee contains caffeine. Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump. Diuretics can also cause lower potassium levels.

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence B
Lamotrigine (Lamictal)

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

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

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

Likelihood Possible Evidence B
Lithium

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

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

Theoretically, coffee might reduce the effects of pentobarbital.
Coffee contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenylpropanolamine

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

Likelihood Probable Evidence B
Pioglitazone (Actos)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Stimulant Drugs

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

Likelihood Probable Evidence C
Theophylline

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

Likelihood Probable Evidence B

Algae Oil3 drug types · 375 drugs

Antidiabetes Drugs

Theoretically, taking algal oil with antidiabetes drugs might interfere with the effects of antidiabetes drugs and reduce their effects.
Most algal oil contains docosahexaenoic acid (DHA). Clinical research in people with type 2 diabetes, including those taking antidiabetes drugs, shows that taking DHA 4 grams daily for 6 weeks increases fasting blood glucose levels by about 18 mg/dL when compared with taking olive oil.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking algal oil with antihypertensive drugs might increase the risk of hypotension.
Algal oil usually contains docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). There is evidence that fish oil, which also contains DHA and EPA, can modestly lower blood pressure and might have additive effects in patients treated with antihypertensive drugs.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, algal oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
The risk of interaction is highest for algal oil containing high amounts (> 2 grams daily) of eicosapentaenoic acid (EPA), or EPA and docosahexaenoic acid (DHA). High doses of EPA or oils containing EPA and DHA can reduce platelet aggregation in humans. However, most algal oil contains very little EPA and larger amounts of DHA. While some conflicting evidence exist, most research shows that DHA alone does not affect blood clotting.

Likelihood Unlikely Evidence D

Chlorophyll2 drug types · 337 drugs

Methotrexate (Trexall, Others)

Theoretically, chlorophyll may reduce the clearance of methotrexate.
In one case report, a 54-year-old male developed delayed clearance of intravenous high-dose methotrexate with concomitant use of chlorophyll. When chlorophyll was stopped 2 days prior to methotrexate treatment, methotrexate clearance was unaffected.

Likelihood Possible Evidence B
Photosensitizing Drugs

Theoretically, concomitant use of chlorophyll with photosensitizing drugs may have additive effects.
Chlorophyll has been reported to cause photosensitization. In two case reports, pseudoporphyria developed after oral intake of chlorophyll. Theoretically, concomitant use with other photosensitizing drugs may exacerbate this effect.

Likelihood Probable Evidence B

Phosphatidylserine2 drug types · 219 drugs

Anticholinergic Drugs

Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.
Phosphatidylserine is thought to increase acetylcholine levels, which could theoretically interfere with the activity of anticholinergic agents.

Likelihood Possible Evidence B
Cholinergic Drugs

Theoretically, phosphatidylserine might have additive effects with cholinergic drugs.
Phosphatidylserine is thought to increase acetylcholine levels, which could theoretically lead to additive cholinergic effects when used with cholinergic drugs.

Likelihood Possible Evidence B

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
The maker

Brand information

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

iwi

See all iwi products
Name
iwi
City
Houston
State
TX
ZipCode
77056
Web Address
iwilife.com
Pharmacist Counseling Corner

Brain by iwi: Common Questions

Does Brain by iwi interact with any medications?
Yes. Based on its ingredients, Brain has a known interaction with 957 medications, including 8 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Brain contains 6 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.
Is iwi Brain safe during pregnancy?
The safety data we hold for chlorophyll and phosphatidylserine advise against use in pregnancy due to insufficient information. Omega-6 fatty acids are rated possibly unsafe in pregnancy. We don't have pregnancy safety data on file for the other ingredients. Talk with your doctor or pharmacist about what's safe for you specifically.
Can I take this while breastfeeding?
Chlorophyll and phosphatidylserine safety during breastfeeding is unknown, so avoidance is recommended unless your doctor advises otherwise. Green coffee bean extract contains caffeine, which passes into breast milk — the data suggests keeping intake low and watching your baby for fussiness or sleep problems. We don't have breastfeeding data for the other ingredients; ask your doctor.
Does green coffee bean extract in this product contain caffeine?
Yes. Green coffee bean extract is made from coffee and contains caffeine. At higher intakes, caffeine can cause jitteriness, anxiety, insomnia, chest pain, and heart palpitations. If you're sensitive to caffeine or take medications affected by it, this ingredient matters.
What does phosphatidylserine do in this product?
Phosphatidylserine is possibly effective for age-related cognitive decline and Alzheimer disease. It's thought to support brain cell function, though the evidence is not conclusive for other uses like ADHD or general cognitive improvement.
Will the omega fatty acids in this product lower my cholesterol?
Omega-6 fatty acids — one of the main components here — are rated possibly ineffective for high cholesterol. The effectiveness of the other omega fatty acids in this formula for cholesterol or heart health is not established in our data. Your doctor can tell you whether an omega supplement makes sense for your situation.
What are the side effects I might notice?
Vitamin B6 may cause headache, nausea, abdominal pain, or vomiting. Phosphatidylserine can cause flatulence, nausea, headache, or insomnia (especially at higher doses). Green coffee bean extract's caffeine can trigger agitation, anxiety, insomnia, or heart palpitations. Chlorophyll may cause sun sensitivity. Most people tolerate these ingredients without problems at normal doses.

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

Not sure if Brain is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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

Brain label
Go deeper

The Full Monographs Behind Brain’s Ingredients

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

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

Chlorophyll

Interacts with 337 drugs

Chlorophyll is the green pigment found in plants and algae, and supplements often use a stable form called chlorophyllin. It is most studied for reducing body and fecal odor and as a topical...

Read the full Chlorophyll monograph →
Herb & supplement monograph

Algal Oil

Interacts with 375 drugs

Algal oil is a plant-based source of the omega-3 fats DHA and (in some products) EPA, making it a popular alternative to fish oil for vegetarians, vegans, and people who dislike fish. There...

Read the full Algal Oil monograph →
Herb & supplement monograph

Omega-6 Fatty Acids

Omega-6 fatty acids are essential fats your body needs but cannot make on its own, and most people get plenty from everyday foods like vegetable oils, nuts, and seeds. Supplements such as ev...

Read the full Omega-6 Fatty Acids monograph →
Herb & supplement monograph

Phosphatidylserine

Interacts with 219 drugs

Phosphatidylserine is a natural fat-like compound found in cell membranes, especially in the brain, and it is sold mainly to support memory and thinking. Some research suggests possible bene...

Read the full Phosphatidylserine monograph →
Herb & supplement monograph

Coffee

Interacts with 591 drugs

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

Read the full Coffee monograph →
Sources

Sources & How We Checked

Brain'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 333 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.

Docosahexaenoic Acid (dha) 49 references
  1. Akedo I, Ishikawa H, Nakamura T, et al. Three cases with familial adenomatous polyposis diagnosed as having malignant lesions in the course of a long-term trial using docosahexanoic acid (DHA)-concentrated fish oil capsules (abstract). Jpn J Clin Oncol PubMed
  2. Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res 1998;1:105-12.
  3. Grimsgaard S, Bonaa KH, Hansen JB, Nordoy A. Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr 1997;66:649-59.
  4. Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911-8.
  5. Sacks FM, Hebert P, Appel LJ, et al. Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the trials of hypertension prevention. J Hypertens 1994;12:209-13.
  6. Vandongen R, Mori TA, Burke V, et al. Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. Hypertension 1993;22:371-9. PubMed
  7. FDA. Center for Food Safety and Applied Nutrition. Letter regarding dietary supplement health claim for omega-3 fatty acids and coronary heart disease. Available at: http://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-Rpt0272-38-Appendix-D-Reference
  8. Pedersen HS, Mulvad G, Seidelin KN, et al. N-3 fatty acids as a risk factor for haemorrhagic stroke. Lancet 1999;353:812-3. PubMed
  9. Ito Y, Suzuki K, Imai H, et al. Effects of polyunsaturated fatty acids on atrophic gastritis in a Japanese population. Cancer Lett 2001;163:171-8. PubMed
  10. Kris-Ehterton PM, Harris WS, Appel LJ, et al. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002;106:2747-57. PubMed
  11. Woodman RJ, Mori TA, Burke V, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 2002;76:1007-15.. PubMed
  12. Marangell LB, Martinez JM, Zboyan HA, et al. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry 2003;160:996-8.. PubMed
  13. Leng GC, Smith FB, Fowkes FG, et al. Relationship between plasma essential fatty acids and smoking, serum lipids, blood pressure and haemostatic and rheological factors. Prostaglandins Leukot Essent Fatty Acids 1994;51:101-8. PubMed
  14. Nelson GJ, Schmidt PS, Bartolini GL, et al. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 1997;32:1129-36. PubMed
  15. Wheaton DH, Hoffman DR, Locke KG, et al. Biological safety assessment of docosahexaenoic acid supplementation in a randomized clinical trial for X-linked retinitis pigmentosa. Arch Ophthalmol 2003;121:1269-78. PubMed
  16. Malcolm CA, McCulloch DL, Montgomery C, et al. Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants: a double blind, prospective, randomised trial. Arch Dis Child Fetal Neonatal Ed 2003;88: DOI
  17. Sanjurjo P, Ruiz-Sanz JI, Jimeno P, et al. Supplementation with docosahexaenoic acid in the last trimester of pregnancy: maternal-fetal biochemical findings. J Perinat Med 2004;32:132-6.
  18. Montgomery C, Speake BK, Cameron A, et al. Maternal docosahexaenoic acid supplementation and fetal accretion. Br J Nutr 2003;90:135-45. DOI
  19. Lauritzen L, Hoppe C, Straarup EM, Michaelsen KF. Maternal fish oil supplementation in lactation and growth during the first 2.5 years of life. Pediatr Res 2005;58:235-42. PubMed
  20. Hawkes JS, Bryan DL, Makrides M, et al. A randomized trial of supplementation with docosahexaenoic acid-rich tuna oil and its effects on the human milk cytokines interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha. Am J Clin Nutr 2002;75:75
  21. Uauy R, Hoffman DR, Mena P, et al. Term infant studies of DHA and ARA supplementation on neurodevelopment: Results of randomized controlled trials. J Pediatr 2003;143:S17-25. PubMed
  22. Decsi, T., Campoy, C., and Koletzko, B. Effect of N-3 polyunsaturated fatty acid supplementation in pregnancy: the Nuheal trial. Adv.Exp Med Biol 2005;569:109-113. PubMed
  23. Mori, T. A., Bao, D. Q., Burke, V., Puddey, I. B., and Beilin, L. J. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 1999;34(2):253-260. PubMed
  24. Otto, S. J., van Houwelingen, A. C., and Hornstra, G. The effect of supplementation with docosahexaenoic and arachidonic acid derived from single cell oils on plasma and erythrocyte fatty acids of pregnant women in the second trimester. Prostaglandins Le PubMed
  25. Helland, I. B., Saugstad, O. D., Smith, L., Saarem, K., Solvoll, K., Ganes, T., and Drevon, C. A. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics 2001;108(5):E82. PubMed
  26. Nestel, P., Shige, H., Pomeroy, S., Cehun, M., Abbey, M., and Raederstorff, D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am.J.Clin.Nutr. 2002;76(2):326-330. PubMed
  27. Woodman, R. J., Mori, T. A., Burke, V., Puddey, I. B., Barden, A., Watts, G. F., and Beilin, L. J. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients PubMed
  28. Jensen, C. L., Voigt, R. G., Prager, T. C., Zou, Y. L., Fraley, J. K., Rozelle, J. C., Turcich, M. R., Llorente, A. M., Anderson, R. E., and Heird, W. C. Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed
  29. Theobald, H. E., Goodall, A. H., Sattar, N., Talbot, D. C., Chowienczyk, P. J., and Sanders, T. A. Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women. J Nutr 2007;137(4):973-978.
  30. Mischoulon D, Best-Popescu C, Laposata M, et al. A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder. Eur Neuropsychopharmacol. 2008;18(9):639-645. PubMed
  31. Birch EE, Carlson SE, Hoffman DR, et al. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexa
  32. Carlson SE, Colombo J, Gajewski BJ, Gustafson KM, Mundy D, Yeast J, Georgieff MK, Markley LA, Kerling EH, Shaddy DJ. DHA supplementation and pregnancy outcomes. Am J Clin Nutr. 2013 Apr;97(4):808-15. PubMed
  33. Escamilla-Nuñez MC, Barraza-Villarreal A, Hernández-Cadena L, Navarro-Olivos E, Sly PD, Romieu I. Omega-3 fatty acid supplementation during pregnancy and respiratory symptoms in children. Chest. 2014 Aug;146(2):373-82. PubMed
  34. Fu YQ, Zheng JS, Yang B, Li D. Effect of individual omega-3 fatty acids on the risk of prostate cancer: a systematic review and dose-response meta-analysis of prospective cohort studies. J Epidemiol. 2015;25(4):261-74. PubMed
  35. Imhoff-Kunsch B, Stein AD, Villalpando S, Martorell R, Ramakrishnan U. Docosahexaenoic acid supplementation from mid-pregnancy to parturition influenced breast milk fatty acid concentrations at 1 month postpartum in Mexican women. J Nutr. 2011 Feb;141(2): PubMed
  36. Judge MP, Cong X, Harel O, Courville AB, Lammi-Keefe CJ. Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: an early neurodevelopmental measure. Early Hum Dev. 2012 Jul;88(7):531-7. PubMed
  37. Mulder KA, King DJ, Innis SM. Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy. PLoS One. 2014 Jan 10;9(1):e83764. PubMed
  38. Richardson AJ, Burton JR, Sewell RP, Spreckelsen TF, Montgomery P. Docosahexaenoic acid for reading, cognition and behavior in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study). PLoS One. 2012;7(9):e43909. PubMed
  39. Drugs in Pregnancy and Lactation 2012;25(4);3-4
  40. FDA announces qualified health claims for omega-3 fatty acids. Available at: https://www.fda.gov/Food/LabelingNutrition/ucm072756.htm. Accessed April 15 2019.
  41. Breastfeeding and the use of human milk. Section on Breastfeeding. Pediatrics. 2012;129(3):e827-41. PubMed
  42. Zhang Z, Fulgoni VL, Kris-Etherton PM, Mitmesser SH. Dietary Intakes of EPA and DHA Omega-3 Fatty Acids among US Childbearing-Age and Pregnant Women: An Analysis of NHANES 2001-2014. Nutrients. 2018;10(4). PubMed
  43. Montgomery P, Spreckelsen TF, Burton A, Burton JR, Richardson AJ. Docosahexaenoic acid for reading, working memory and behavior in UK children aged 7-9: A randomized controlled trial for replication (the DOLAB II study). PLoS One. 2018;13(2):e0192909. PubMed
  44. Marc I, Piedboeuf B, Lacaze-Masmonteil T, et al. Effect of maternal docosahexaenoic acid supplementation on bronchopulmonary dysplasia-free survival in breastfed preterm infants: A randomized clinical trial. JAMA. 2020;324(2):157-167. PubMed
  45. Fougère H, Bilodeau JF, Lavoie PM, et al. Docosahexaenoic acid-rich algae oil supplementation on breast milk fatty acid profile of mothers who delivered prematurely: a randomized clinical trial. Sci Rep 2021;11(1):21492. PubMed
  46. Garmendia ML, Casanello P, Flores M, Kusanovic JP, Uauy R. The effects of a combined intervention (docosahexaenoic acid supplementation and home-based dietary counseling) on metabolic control in obese and overweight pregnant women: the MIGHT study. Am J O PubMed
  47. Christifano DN, Gustafson KM, Carlson SE, et al. Maternal docosahexaenoic acid exposure needed to achieve maternal-newborn EQ. Nutrients 2022;14(16):3300. PubMed
  48. Vizzari G, Morniroli D, Alessandretti F, et al. Comparative analysis of docosahexaenoic acid (DHA) content in mother's milk of term and preterm mothers. Nutrients 2022;14(21):4595. PubMed
  49. Yang Y, Li G, Li F, et al. Impact of DHA from algal oil on the breast milk DHA levels of lactating women: A randomized controlled trial in China. Nutrients 2022;14(16):3410. PubMed

See these in context on the Docosahexaenoic Acid (dha) 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 →

Chlorophyll 5 references
  1. Mathews-Roth MM. Carotenoids in erythropoietic protoporphyria and other photosensitivity diseases. Ann N Y Acad Sci, 1993; 691:127-38. PubMed
  2. Belen'kii, G. B. and Krikun, B. L. [Treatment of herpes simplex and herpes zoster by chlorophyll preparations]. Sov.Med. 1971;34(1):151-152.
  3. Brooks SL, Sanders J, Seymour JF, Mellor JD. A case of delayed methotrexate clearance following administration of a complementary medication containing chlorophyll. J Oncol Pharm Pract. 2014 Jun;20(3):225-8. PubMed
  4. Rossi E, Borchard K, Cole JM. Pseudoporphyria following self-medication with chlorophyll. Australas J Dermatol. 2015 Feb;56(1):47-8. PubMed
  5. Zhao CY, Frew JW, Muhaidat J, et al. Chlorophyll-induced pseudoporphyria with ongoing photosensitivity after cessation - a case series of four patients. J Eur Acad Dermatol Venereol 2016;30(7):1239-42. PubMed

See these in context on the Chlorophyll monograph →

Omega-6 Fatty Acids 20 references
  1. Godley PA. Essential fatty acid consumption and risk of breast cancer. Breast Cancer Res Treat 1995;35:91-5. PubMed
  2. Newcomer LM, King IB, Wicklund KG, Stanford JL. The association of fatty acids with prostate cancer risk. Prostate 2001;47:262-8. DOI
  3. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate. Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academy Press, 2005. Available at: http://www.nap.edu/books/03 DOI
  4. Colter, A. L., Cutler, C., and Meckling, K. A. Fatty acid status and behavioural symptoms of attention deficit hyperactivity disorder in adolescents: a case-control study. Nutr J 2008;7:8. PubMed
  5. Yamada, T., Strong, J. P., Ishii, T., Ueno, T., Koyama, M., Wagayama, H., Shimizu, A., Sakai, T., Malcom, G. T., and Guzman, M. A. Atherosclerosis and omega-3 fatty acids in the populations of a fishing village and a farming village in Japan. Atheroscler
  6. Conklin, S. M., Manuck, S. B., Yao, J. K., Flory, J. D., Hibbeln, J. R., and Muldoon, M. F. High omega-6 and low omega-3 fatty acids are associated with depressive symptoms and neuroticism. Psychosom.Med. 2007;69(9):932-934.
  7. Richardson, A. J., Cyhlarova, E., and Ross, M. A. Omega-3 and omega-6 fatty acid concentrations in red blood cell membranes relate to schizotypal traits in healthy adults. Prostaglandins Leukot.Essent.Fatty Acids 2003;69(6):461-466. PubMed
  8. Assies, J., Lok, A., Bockting, C. L., Weverling, G. J., Lieverse, R., Visser, I., Abeling, N. G., Duran, M., and Schene, A. H. Fatty acids and homocysteine levels in patients with recurrent depression: an explorative pilot study. Prostaglandins Leukot.Es PubMed
  9. Chiplonkar, S. A., Agte, V. V., Tarwadi, K. V., Paknikar, K. M., and Diwate, U. P. Micronutrient deficiencies as predisposing factors for hypertension in lacto-vegetarian Indian adults. J Am Coll.Nutr 2004;23(3):239-247. PubMed
  10. Mamalakis, G., Kiriakakis, M., Tsibinos, G., Hatzis, C., Flouri, S., Mantzoros, C., and Kafatos, A. Depression and serum adiponectin and adipose omega-3 and omega-6 fatty acids in adolescents. Pharmacol.Biochem.Behav. 2006;85(2):474-479. PubMed
  11. Okuyama, H., Ichikawa, Y., Sun, Y., Hamazaki, T., and Lands, W. E. Cancers common in the USA are stimulated by omega 6 fatty acids and large amounts of animal fats, but suppressed by omega 3 fatty acids and cholesterol. World Rev Nutr Diet. 2007;96:143-1
  12. Martinez-Ramirez, M. J., Palma, S., Martinez-Gonzalez, M. A., Delgado-Martinez, A. D., de la Fuente, C., and Delgado-Rodriguez, M. Dietary fat intake and the risk of osteoporotic fractures in the elderly. Eur.J Clin Nutr 2007;61(9):1114-1120. PubMed
  13. Sonestedt, E., Gullberg, B., and Wirfalt, E. Both food habit change in the past and obesity status may influence the association between dietary factors and postmenopausal breast cancer. Public Health Nutr 2007;10(8):769-779. PubMed
  14. Simopoulos, A. P. The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease. Asia Pac.J Clin Nutr 2008;17 Suppl 1:131-134.
  15. Harris, W. S., Mozaffarian, D., Rimm, E., Kris-Etherton, P., Rudel, L. L., Appel, L. J., Engler, M. M., Engler, M. B., and Sacks, F. Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition DOI
  16. Godley, P. A., Campbell, M. K., Gallagher, P., Martinson, F. E., Mohler, J. L., and Sandler, R. S. Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma. Cancer Epidemiol.Biomarkers Prev. 1996;5(11):889-895.
  17. Lee E, Kim H, Kim H, Ha EH, Chang N. Association of maternal omega-6 fatty acid intake with infant birth outcomes: Korean Mothers and Children's Environmental Health (MOCEH). Nutr J 2018;17(1):47. PubMed
  18. Pawelczyk T, Trafalska E, Pawelczyk A, Kotlicka-Antczak M. Differences in omega-3 and omega-6 polyunsaturated fatty acid consumption in people at ultra-high risk of psychosis, first-episode schizophrenia, and in healthy controls. Early Interv Psychiatry 2
  19. Gardner KG, Gebretsadik T, Hartman TJ, et al. Prenatal omega-3 and omega-6 polyunsaturated fatty acids and childhood atopic dermatitis. J Allergy Clin Immunol Pract. 2020;8(3):937-944. PubMed
  20. Luo J, Ge H, Sun J, Hao K, Yao W, Zhang D. Associations of dietary ?-3, ?-6 fatty acids consumption with sleep disorders and sleep duration among adults. Nutrients 2021;13(5):1475. PubMed

See these in context on the Omega-6 Fatty Acids monograph →

Algal Oil 43 references
  1. Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res 1998;1:105-12.
  2. Grimsgaard S, Bonaa KH, Hansen JB, Nordoy A. Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr 1997;66:649-59.
  3. Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911-8.
  4. Sacks FM, Hebert P, Appel LJ, et al. Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the trials of hypertension prevention. J Hypertens 1994;12:209-13.
  5. Vandongen R, Mori TA, Burke V, et al. Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. Hypertension 1993;22:371-9. PubMed
  6. FDA. Center for Food Safety and Applied Nutrition. Letter regarding dietary supplement health claim for omega-3 fatty acids and coronary heart disease. Available at: http://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-Rpt0272-38-Appendix-D-Reference
  7. Leaf A. On the reanalysis of the GISSI-Prevenzione. Circulation 2002;105:1874-5. PubMed
  8. Connor WE. n-3 Fatty acids from fish and fish oil: panacea or nostrum? Am J Clin Nutr 2001;74;415-6. PubMed
  9. Calder PC. N-3 polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutr Res 2001;21:309-41. DOI
  10. Pedersen HS, Mulvad G, Seidelin KN, et al. N-3 fatty acids as a risk factor for haemorrhagic stroke. Lancet 1999;353:812-3. PubMed
  11. Terano T, Hirai A, Hamazaki T, et al. Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects. Atherosclerosis 1983;46:321-31.. PubMed
  12. Kris-Ehterton PM, Harris WS, Appel LJ, et al. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002;106:2747-57. PubMed
  13. Woodman RJ, Mori TA, Burke V, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 2002;76:1007-15.. PubMed
  14. Marangell LB, Martinez JM, Zboyan HA, et al. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry 2003;160:996-8.. PubMed
  15. Leng GC, Smith FB, Fowkes FG, et al. Relationship between plasma essential fatty acids and smoking, serum lipids, blood pressure and haemostatic and rheological factors. Prostaglandins Leukot Essent Fatty Acids 1994;51:101-8. PubMed
  16. Nelson GJ, Schmidt PS, Bartolini GL, et al. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 1997;32:1129-36. PubMed
  17. Wheaton DH, Hoffman DR, Locke KG, et al. Biological safety assessment of docosahexaenoic acid supplementation in a randomized clinical trial for X-linked retinitis pigmentosa. Arch Ophthalmol 2003;121:1269-78. PubMed
  18. Svaneborg N, Kristensen SD, Hansen LM, et al. The acute and short-time effect of supplementation with the combination of n-3 fatty acids and acetylsalicylic acid on platelet function and plasma lipids. Thromb Res 2002;105:311-6. PubMed
  19. Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;369:1090-8. PubMed
  20. von Houwelingen R, Nordøy A, van der Beek E, et al. Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males. Am J Clin Nutr. 1987 Sep;46(3):424-36. PubMed
  21. Goodnight SH Jr, Harris WS, Connor WE. The effects of dietary omega 3 fatty acids on platelet composition and function in man: a prospective, controlled study. Blood. 1981 Nov;58(5):880-5. DOI
  22. Mori, T. A., Bao, D. Q., Burke, V., Puddey, I. B., and Beilin, L. J. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 1999;34(2):253-260. PubMed
  23. Nestel, P., Shige, H., Pomeroy, S., Cehun, M., Abbey, M., and Raederstorff, D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am.J.Clin.Nutr. 2002;76(2):326-330. PubMed
  24. Woodman, R. J., Mori, T. A., Burke, V., Puddey, I. B., Barden, A., Watts, G. F., and Beilin, L. J. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients PubMed
  25. Theobald, H. E., Goodall, A. H., Sattar, N., Talbot, D. C., Chowienczyk, P. J., and Sanders, T. A. Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women. J Nutr 2007;137(4):973-978.
  26. Mischoulon D, Best-Popescu C, Laposata M, et al. A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder. Eur Neuropsychopharmacol. 2008;18(9):639-645. PubMed
  27. Arterburn, L. M., Oken, H. A., Bailey, Hall E., Hamersley, J., Kuratko, C. N., and Hoffman, J. P. Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid. J Am Diet Assoc 2008;108(7):1204-1209. PubMed
  28. Zucker, M. L., Bilyeu, D. S., Helmkamp, G. M., Harris, W. S., and Dujovne, C. A. Effects of dietary fish oil on platelet function and plasma lipids in hyperlipoproteinemic and normal subjects. Atherosclerosis 1988;73(1):13-22. PubMed
  29. Bernstein AM, Ding EL, Willett WC, Rimm EB. A meta-analysis shows that docosahexaenoic acid from algal oil reduces serum triglycerides and increases HDL-cholesterol and LDL-cholesterol in persons without coronary heart disease. J Nutr. 2012;142(1):99-104.
  30. Carlson SE, Colombo J, Gajewski BJ, Gustafson KM, Mundy D, Yeast J, Georgieff MK, Markley LA, Kerling EH, Shaddy DJ. DHA supplementation and pregnancy outcomes. Am J Clin Nutr. 2013 Apr;97(4):808-15. PubMed
  31. Fu YQ, Zheng JS, Yang B, Li D. Effect of individual omega-3 fatty acids on the risk of prostate cancer: a systematic review and dose-response meta-analysis of prospective cohort studies. J Epidemiol. 2015;25(4):261-74. PubMed
  32. Imhoff-Kunsch B, Stein AD, Villalpando S, Martorell R, Ramakrishnan U. Docosahexaenoic acid supplementation from mid-pregnancy to parturition influenced breast milk fatty acid concentrations at 1 month postpartum in Mexican women. J Nutr. 2011 Feb;141(2): PubMed
  33. Mulder KA, King DJ, Innis SM. Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy. PLoS One. 2014 Jan 10;9(1):e83764. PubMed
  34. Richardson AJ, Burton JR, Sewell RP, Spreckelsen TF, Montgomery P. Docosahexaenoic acid for reading, cognition and behavior in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study). PLoS One. 2012;7(9):e43909. PubMed
  35. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardi PubMed
  36. FDA announces qualified health claims for omega-3 fatty acids. Available at: https://www.fda.gov/Food/LabelingNutrition/ucm072756.htm. Accessed April 15 2019.
  37. Breastfeeding and the use of human milk. Section on Breastfeeding. Pediatrics. 2012;129(3):e827-41. PubMed
  38. Zhang Z, Fulgoni VL, Kris-Etherton PM, Mitmesser SH. Dietary Intakes of EPA and DHA Omega-3 Fatty Acids among US Childbearing-Age and Pregnant Women: An Analysis of NHANES 2001-2014. Nutrients. 2018;10(4). PubMed
  39. Montgomery P, Spreckelsen TF, Burton A, Burton JR, Richardson AJ. Docosahexaenoic acid for reading, working memory and behavior in UK children aged 7-9: A randomized controlled trial for replication (the DOLAB II study). PLoS One. 2018;13(2):e0192909. PubMed
  40. Rao A, Briskey D, Nalley JO, Ganuza E. Omega-3 eicosapentaenoic acid (EPA) rich extract from the microalga Nannochloropsis decreases cholesterol in healthy individuals: A double-blind, randomized, placebo-controlled, three-month supplementation study. Nut PubMed
  41. Marc I, Piedboeuf B, Lacaze-Masmonteil T, et al. Effect of maternal docosahexaenoic acid supplementation on bronchopulmonary dysplasia-free survival in breastfed preterm infants: A randomized clinical trial. JAMA. 2020;324(2):157-167. PubMed
  42. Fougère H, Bilodeau JF, Lavoie PM, et al. Docosahexaenoic acid-rich algae oil supplementation on breast milk fatty acid profile of mothers who delivered prematurely: a randomized clinical trial. Sci Rep 2021;11(1):21492. PubMed
  43. Yang Y, Li G, Li F, et al. Impact of DHA from algal oil on the breast milk DHA levels of lactating women: A randomized controlled trial in China. Nutrients 2022;14(16):3410. PubMed

See these in context on the Algal Oil monograph →

Phosphatidylserine 9 references
  1. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull 1992;28:61-6.
  2. Pepping J. Phosphatidylserine. Am J Health-Syst Pharm 1999;56:2038,2043-4.
  3. Kidd PM. Phosphatidylserine; Membrane nutrient for memory. A clinical and mechanistic assessment. Altern Med Rev 1996;1:70-84.
  4. Kim HY, Akbar M, Lau A, et al. Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3). Role of phosphatidylserine in antiapoptotic effect. J Biol Chem 2000;275:35215-23.. PubMed
  5. Zanotti A, Valzelli L, Toffano G. Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. Psychopharmacology (Berl) 1989;99:316-21.. PubMed
  6. Schreiber S, Kampf-Sherf O, Gorfine M, et al. An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37:302-7.
  7. Pepping, J. Phosphatidylserine. Am J Health Syst.Pharm. 10-15-1999;56(20):2038, 2043-2038, 2044.
  8. Monteverde, A., Gnemmi, P., Rossi, F., Monteverde, A., and Finali, G. C. Selegiline in the treatment of mild to moderate Alzheimer-type dementia. Clin.Ther 1990;12(4):315-322.
  9. Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geri PubMed

See these in context on the Phosphatidylserine monograph →

Coffee 175 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricylic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984;73:1056-8. PubMed
  8. Kulhanek F, Linde OK, Meisenberg G. Precipitation of antipsychotic drugs in interaction with coffee or tea. Lancet 1979;2:1130.
  9. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  10. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  11. Grubben MJ, Boers GH, Blom HJ, et al. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. Am J Clin Nutr 2000;71:480-4. PubMed
  12. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  13. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  14. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  15. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  16. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  17. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  18. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed
  19. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  20. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. PubMed
  21. Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. PubMed
  22. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  23. Margolin KA, Green MR. Polymicrobial enteric septicemia from coffee enemas. West J Med 1984;140:460.
  24. Urgert R, Vliet TV, Zock PL, et al. Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers. Am J Clin Nutr 2000;72:1107-10. PubMed
  25. Green S. A critique of the rationale for cancer treatment with coffee enemas and diet. JAMA 1992;268:3224-7. DOI
  26. Shils ME, Herman MG. Unproved dietary claims in the treatment of patients with cancer. Bull N Y Acad Med 1982;58:323-39.
  27. Boozer CN, Nasser JA, Heymsfield SB, et al. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001;25:316-24. PubMed
  28. Bak AA, Grobbee DE. The effect of serum cholesterol levels of coffee brewed by filtering or boiling. N Engl J Med 1989;321:1432-7.
  29. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  30. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  31. Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. PubMed
  32. Lloyd T, Johnson-Rollings N, Eggli DF, et al. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr 2000;19:256-61. PubMed
  33. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  34. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  35. Heliovaara M, Aho K, Knekt P, et al. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann Rheum Dis 2000;59:631-5. PubMed
  36. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  37. Brown BT. Treating cancer with coffee enemas and diet. JAMA 1993;269:1635-6. DOI
  38. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  39. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  40. Samarrae WA, Truswell AS. Short-term effect of coffee on blood fibrinolytic activity in healthy adults. Atherosclerosis 1977;26:255-60. PubMed
  41. Klag MJ, Wang NY, Meoni LA, et al. Coffee intake and risk of hypertension: The John Hopkins precursors study. Arch Intern Med 2002;162:657-62. DOI
  42. Brenner H, Rothenbacher D, Bode G, Adler G. Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study. BMJ 1997;315:1489-92.
  43. Jee SH, He J, Appel LJ, et al. Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 2001:153:353-62. PubMed
  44. Michaud DS, Giovannucci E, Willett WC, et al. Coffee and alcohol consumption and risk of pancreatic cancer in two prospective United States cohorts. Cancer Epidemiol Biomarkers Prev 2001;10:429-37.
  45. Tavani A, Pregnolato A, La Vecchia C, et al. Coffee consumption and the risk of breast cancer. Eur J Cancer Prev 1998;7:77-82.
  46. Tavani A, La Vecchia C. Coffee and cancer: a review of epidemiological studies, 1990-1999. Eur J Cancer Prev 2000;9:241-56.
  47. Hartman TJ, Tangrea JA, Pietinen P, et al. Tea and coffee consumption and risk of colon and rectal cancer in middle-aged Finnish men. Nutr Cancer 1998;31:41-8. PubMed
  48. Anon. Filtering the news about coffee. University of California, Berkeley Wellness Letter 2001:17:1-2.
  49. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 1996:144:642-4. PubMed
  50. Jacobsen BK, Heuch I. Coffee, K-ras mutations and pancreatic cancer: a heterogeneous aetiology or an artefact? J Epidemiol Community Health 2000;54:654-5.
  51. Porta M, Malats N, Alguacil J, et al. Coffee, pancreatic cancer, and K-ras mutations: updating the research agenda. J Epidemiol Community Health 2000;54:656-9.
  52. Kuper HE, Mucci LA, Trichopoulos D. Coffee, pancreatic cancer, and the question of causation. J Epidemiol Community Health 2000;54:650-1.
  53. Urgert R, Meyboom S, Kuilman M, et al. Comparison of effect of cafetiere and filtered coffee on serum concentrations of liver aminotransferases and lipids: six month randomised controlled trial. BMJ 1996;313:1362-6.. DOI
  54. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. PubMed
  55. Horner NK, Lampe JW. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness. J Am Diet Assoc 2000;100:1368-80. PubMed
  56. Bracken MB, Triche EW, Belanger K, et al. Association of maternal caffeine consumption with decrements in fetal growth. Am J Epidemiol 2003;157:456-66.. PubMed
  57. Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003;289:1537-45.. PubMed
  58. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  59. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  60. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  61. Wisborg K, Kesmodel U, Bech BH, et al. Maternal consumption of coffee during pregnancy and stillbirth and infant death in first year of life: prospective study. BMJ 2003;326:420.. PubMed
  62. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI
  63. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  64. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  65. Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J Nutr 2003;133:3228-32. PubMed
  66. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  67. Food and Nutrition Board, Institute of Medicine. Nutrition during lactation. Washington, DC: National Academy Press, 1991. Available at: http://books.nap.edu/books/0309043913/html.
  68. Gertz BJ, Holland SD, Kline WF, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther 1995;58:288-98. PubMed
  69. May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982;31:656-61. PubMed
  70. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. PubMed
  71. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  72. Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. DOI
  73. Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. PubMed
  74. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  75. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  76. Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. PubMed
  77. Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7.
  78. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
  79. Holmgren P, Norden-Pettersson L, Ahlner J. Caffeine fatalities--four case reports. Forensic Sci Int 2004;139:71-3. PubMed
  80. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  81. Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. PubMed
  82. Sato J, Nakata H, Owada E, et al. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol 1993;44:295-8. PubMed
  83. Baker JA, McCann SE, Reid ME, et al. Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers. Nutr Cancer 2005;52:15-21. PubMed
  84. Benowitz NL, Osterloh J, Goldschlager N, et al. Massive catecholamine release from caffeine poisoning. JAMA 1982;248:1097-8. DOI
  85. Leson CL, McGuigan MA, Bryson SM. Caffeine overdose in an adolescent male. J Toxicol Clin Toxicol 1988;26:407-15. PubMed
  86. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004;176:1-29. PubMed
  87. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  88. Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. DOI
  89. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  90. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  91. Lopez-Garcia E, van Dam RM, Willett WC, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 2006;113:2045-53. PubMed
  92. Baylin A, Hernandez-Diaz S, Kabagambe EK, et al. Transient exposure to coffee as a trigger of a first nonfatal myocardial infarction. Epidemiology 2006;17:506-11. PubMed
  93. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8. PubMed
  94. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  95. Benvenga S. Bartolone L, Pappalardo MA, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid 2008;18:293-301. PubMed
  96. Stille, W., Harder, S., Mieke, S., Beer, C., Shah, P. M., Frech, K., and Staib, A. H. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J.Antimicrob.Chemother. 1987;20(5):729-734. PubMed
  97. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  98. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.
  99. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  100. Azcona O, Barbanoi MJ, Torrent J, Jane F. Evaluation of the central effects of alcohol and caffeine interaction. Br J Clin Pharmacol 1995;40:393-400. PubMed
  101. Harder S, Staib AH, Beer C, et al. 4-quinolones inhibit biotransformation of caffeine. Eur J Clin Pharmacol 1988;35:651-6. PubMed
  102. Zhang LL, Zhang JR, Guo K, et al. Effects of fluoroquinolones on CYP4501A and 3A in male broilers. Res Vet Sci 2011;90:99-105. PubMed
  103. Cesana M, Broccali G, Imbimbo BP, Crema A. Effect of single doses of rufloxacin on the disposition of theophylline and caffeine after single administration. Int J Clin Pharmacol Ther Toxicol 1991:29:133-8.
  104. Broughton LJ, Rogers HJ. Decreased systemic clearance of caffeine due to cimetidine. Br J Clin Pharmacol 1981;12:155-9. PubMed
  105. Smits P, Straatman C, Pijpers E, Thien T. Dose-dependent inhibition of the hemodynamic response to dipyridamole by caffeine. Clin Pharmacol Ther 1991;50:529-37. PubMed
  106. Zelenitsky SA, Norman A, Nix DE. The effects of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. J Infect Dis Pharmacother 1995;1:1-11.
  107. Joeres R, Richter E. Mexiletine and caffeine elimination. N Engl J Med 1987;317:117. PubMed
  108. Jonkman JH, Sollie FA, Sauter R, Steinijans VW. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther 1991;49:248-55. PubMed
  109. Smits, P., Temme, L., and Thien, T. The cardiovascular interaction between caffeine and nicotine in humans. Clin Pharmacol Ther 1993;54(2):194-204. PubMed
  110. MacKenzie, T., Comi, R., Sluss, P., Keisari, R., Manwar, S., Kim, J., Larson, R., and Baron, J. A. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-1698. PubMed
  111. Lopez-Garcia, E., Rodriguez-Artalejo, F., Rexrode, K. M., Logroscino, G., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of stroke in women. Circulation 3-3-2009;119(8):1116-1123. PubMed
  112. Zhang, W., Lopez-Garcia, E., Li, T. Y., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of cardiovascular diseases and all-cause mortality among men with type 2 diabetes. Diabetes Care 2009;32(6):1043-1045. PubMed
  113. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433. PubMed
  114. Moisey, L. L., Robinson, L. E., and Graham, T. E. Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males. Br.J Nutr. 2010;103(6):833-841. PubMed
  115. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  116. Buscemi, S., Verga, S., Batsis, J. A., Donatelli, M., Tranchina, M. R., Belmonte, S., Mattina, A., Re, A., and Cerasola, G. Acute effects of coffee on endothelial function in healthy subjects. Eur.J Clin Nutr. 2010;64(5):483-489. PubMed
  117. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  118. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  119. Banko, L. T., Haq, S. A., Rainaldi, D. A., Klem, I., Siegler, J., Fogel, J., Sacchi, T. J., and Heitner, J. F. Incidence of caffeine in serum of patients undergoing dipyridamole myocardial perfusion stress test by an intensive versus routine caffeine his
  120. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  121. Conen, D., Chiuve, S. E., Everett, B. M., Zhang, S. M., Buring, J. E., and Albert, C. M. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr 2010;92(3):509-514. PubMed
  122. Reis, J. P., Loria, C. M., Steffen, L. M., Zhou, X., van, Horn L., Siscovick, D. S., Jacobs, D. R., Jr., and Carr, J. J. Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study. A PubMed
  123. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  124. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  125. Mostofsky, E., Schlaug, G., Mukamal, K. J., Rosamond, W. D., and Mittleman, M. A. Coffee and acute ischemic stroke onset: the Stroke Onset Study. Neurology 11-2-2010;75(18):1583-1588. PubMed
  126. Orozco-Gregorio, H., Mota-Rojas, D., Bonilla-Jaime, H., Trujillo-Ortega, M. E., Becerril-Herrera, M., Hernandez-Gonzalez, R., and Villanueva-Garcia, D. Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia PubMed
  127. Li, G. Z., Zhang, N., Du, P., Yang, Y., Wu, S. L., Xiao, Y. X., Jin, R., Liu, L., Shen, H., and Dai, Y. Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms: a Chinese multi-center study. Chin Med
  128. Smits, P., Lenders, J. W., and Thien, T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin.Pharmacol.Ther. 1990;48(4):410-418. PubMed
  129. Rossignol, A. M. and Bonnlander, H. Caffeine-containing beverages, total fluid consumption, and premenstrual syndrome. Am.J.Public Health 1990;80(9):1106-1110. PubMed
  130. Jeppesen, U., Loft, S., Poulsen, H. E., and Brsen, K. A fluvoxamine-caffeine interaction study. Pharmacogenetics 1996;6(3):213-222. PubMed
  131. Smits, P., Corstens, F. H., Aengevaeren, W. R., Wackers, F. J., and Thien, T. False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion. J Nucl.Med. 1991;32(8):1538-1541. DOI
  132. Wang Y, Yu X, Wu Y, Zhang D. Coffee and tea consumption and risk of lung cancer: a dose-response analysis of observational studies. Lung Cancer. 2012;78(2):169-70. PubMed
  133. Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J. Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart. 2013;99(19):1383-9. doi: 10.1136/heartjnl-2013-303950. Re PubMed
  134. Cheng M, Hu Z, Lu X, Huang J, Gu D. Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies. Can J Cardiol. 2014 Apr;30(4):448-54. doi: 10.1016/j.cjca.2013.12.026. Epub 2014 2. Review. PubMed
  135. Chiaffarino F, Bravi F, Cipriani S, Parazzini F, Ricci E, Viganò P, La Vecchia C. Coffee and caffeine intake and risk of endometriosis: a meta-analysis. Eur J Nutr. 2014 Oct;53(7):1573-9. doi: 10.1007/s00394-014-0662-7. Epub 2014 31. PubMed
  136. Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies. Gynecol Oncol. 2013 Jun;129(3):620-9. doi: 10.1016/j.ygyno.2013.03.014. Epub 2013 25. Review. PubMed
  137. Sanikini H, Dik VK, Siersema PD, Bhoo-Pathy N, Uiterwaal CS, Peeters PH, González CA, Zamora-Ros R, Overvad K, Tjønneland A, Roswall N, Boutron-Ruault MC, Fagherazzi G, Racine A, Kühn T, Katzke V, Boeing H, Trichopoulou A, Trichopoulos D, Lagiou P, Palli
  138. van der Hoeven N, Visser I, Schene A, van den Born BJ. Severe hypertension related to caffeinated coffee and tranylcypromine: a case report. Ann Intern Med. 2014 May 6;160(9):657-8. doi: 10.7326/L14-5009-8. No abstract available. PubMed
  139. Dixit S, Stein PK, Dewland TA, Dukes JW, Vittinghoff E, Heckbert SR, Marcus GM. Consumption of Caffeinated Products and Cardiac Ectopy. J Am Heart Assoc. 2016 26;5(1). pii: e002503. doi: 10.1161/JAHA.115.002503. PubMed
  140. Turati F, Galeone C, Talamini R, et al. Coffee, decaffeinated coffee, tea, and pancreatic cancer risk: a pooled-analysis of two Italian case-control studies. Eur J Cancer Prev 2011;20(4):287-92. PubMed
  141. Zuchinali P, Riberio PA, Pimentel M, da Rosa PR, Zimerman LI, Rohde LE. Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies. Europace 2016 Feb;18(2):257-66. PubMed
  142. Acosta RD, Cash BD. Clinical effects of colonic cleansing for general health promotion: a systematic review. Am J Gastroenterol. 2009;104(11):2830-6. PubMed
  143. Kunitake Y, Mizoguchi Y, Sogawa R, et al. Effect of excessive coffee consumption on the clinical course of a patient with bipolar disorder: a case report and literature review. Clin Neuropharmacol. 2017 Jul/Aug;40(4):160-162. doi: 10.1097/WNF.00000000 PubMed
  144. Crippa A, Discacciati A, Larsson SC, Wolk A, Orsini N. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am J Epidemiol. 2014 Oct 15;180(8):763-75. doi: 10.1093/aje/kwu194. PubMed
  145. Loftfield E, Cornelis MC, Caporaso N, Yu K, Sinha R, Freedman N. Association of coffee drinking With mortality by genetic variation in caffeine metabolism: findings from the UK biobank. JAMA Intern Med. 2018 Aug 1;178(8):1086-1097. doi: 10.1001/jamaintern PubMed
  146. Lagier D, Nee L, Guieu R, et al. Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: a randomized controlled clinical trial. Eur J Anaesthesiol. 2018 Apr 26. [Epub ahead of DOI
  147. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  148. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648. PubMed
  149. Lee AH, Kabashneh S, Tsouvalas CP, et al. Proctocolitis from coffee enema. ACG Case Rep J. 2020;7(1):e00292. PubMed
  150. Tverdal A, Selmer R, Cohen JM, Thelle DS. Coffee consumption and mortality from cardiovascular diseases and total mortality: Does the brewing method matter? Eur J Prev Cardiol. 2020:2047487320914443. PubMed
  151. Yamakawa M, Wada K, Goto Y, et al. Associations between coffee consumption and all-cause and cause-specific mortality in a Japanese city: the Takayama study. Public Health Nutr. 2019;22(14):2561-2568. PubMed
  152. Zhou CD, Kuan AS, Reeves GK, et al. Coffee and pancreatic cancer risk among never-smokers in the UK prospective Million Women Study. Int J Cancer. 2019;145(6):1484-1492. PubMed
  153. Stojanovic E, Scanlan AT, Milanovic Z, Fox JL, Stankovic R, Dalbo VJ. Acute caffeine supplementation improves jumping, sprinting, and change-of-direction performance in basketball players when ingested in the morning but not evening. Eur J Sport Sci. 2021 PubMed
  154. Ruggiero E, Di Castelnuovo A, Costanzo S, et al. Daily coffee drinking is associated with lower risks of cardiovascular and total mortality in a general Italian population: Results from the Moli-sani study. J Nutr. 2020:nxaa365. PubMed
  155. Kim Y, Je Y, Giovannucci E. Coffee consumption and all-cause and cause-specific mortality: a meta-analysis by potential modifiers. Eur J Epidemiol. 2019 Aug;34(8):731-752. doi: 10.1007/s10654-019-00524-3. Epub 2019 May 4. PubMed
  156. Stevens LM, Linstead E, Hall JL, Kao DP. Association between coffee intake and incident heart failure risk: A machine learning analysis of the FHS, the ARIC Study, and the CHS. Circ Heart Fail. 2021:CIRCHEARTFAILURE119006799. PubMed
  157. Ribeiro EM, Alves M, Costa J, Ferreira JJ, Pinto FJ, Caldeira D. Safety of coffee consumption after myocardial infarction: A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis. 2020;30(12):2146-2158. PubMed
  158. Grosso G, Micek A, Godos J, ET AL. Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: a dose-response meta-analysis. Eur J Epidemiol. 2016;31(12):1191-1205. PubMed
  159. Kim EJ, Hoffmann TJ, Nah G, Vittinghoff E, Delling F, Marcus GM. Coffee consumption and incident tachyarrhythmias: Reported behavior, mendelian randomization, and their interactions. JAMA Intern Med. 2021. PubMed
  160. Loftfield E, Freedman ND, Graubard BI, et al. Association of coffee consumption with overall and cause-specific mortality in a large US prospective cohort study. Am J Epidemiol. 2015;182(12):1010-22. PubMed
  161. Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E. The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis. Am J Clin Nutr. 2011;94(4):1113-26. PubMed
  162. Miranda AM, Goulart AC, Benseñor IM, Lotufo PA, Marchioni DM. Moderate coffee consumption is associated with lower risk of mortality in prior Acute Coronary Syndrome patients: a prospective analysis in the ERICO cohort. Int J Food Sci Nutr. 2020:1-11.
  163. Nordestgaard AT, Nordestgaard BG. Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95?000-223?000 individuals. Int J Epidemiol. 2016;45(6):1938-1952. PubMed
  164. Zhang Y, Yang H, Li S, Li WD, Wang Y. Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLoS Med 2021;18(11):e1003830. PubMed
  165. Chan L, Hong CT, Bai CH. Coffee consumption and the risk of cerebrovascular disease: a meta-analysis of prospective cohort studies. BMC Neurol 2021;21(1):380. PubMed
  166. Welty TE, Gidal BE, Duan J, et al. Coffee and cigarette smoking interactions with lamotrigine. Epilepsy Behav 2021;116:107741. PubMed
  167. Zheng KH, Zhu K, Wactawski-Wende J, et al. Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative. Int J Cancer 2021;149(12):2032-2044. PubMed
  168. Wang S, Li X, Yang Y, et al. Does coffee, tea and caffeine consumption reduce the risk of incident breast cancer? A systematic review and network meta-analysis. Public Health Nutr 2021;24(18):6377-6389. PubMed
  169. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Saudi Med J 2021;42(2):151-160. PubMed
  170. Gleason JL, Sundaram R, Mitro SD, et al. Association of maternal caffeine consumption during pregnancy with child growth. JAMA Netw Open. 2022;5(10):e2239609. PubMed
  171. Teramoto M, Yamagishi K, Muraki I, Tamakoshi A, Iso H. Coffee and green tea consumption and cardiovascular disease mortality among people with and without hypertension. J Am Heart Assoc 2023;12(2):e026477. PubMed
  172. Han M, Oh Y, Myung SK. Coffee intake and risk of hypertension: A meta-analysis of cohort studies. J Korean Med Sci 2022;37(45):e332. PubMed
  173. Sehrawat O, Mehra NS, Kowlgi NG, et al. Association between coffee consumption and incident atrial fibrillation (from the Multi-Ethnic Study of Atherosclerosis [MESA]). Am J Cardiol 2023;186:5-10. PubMed
  174. Marcus GM, Rosenthal DG, Nah G, et al. Acute effects of coffee consumption on health among ambulatory adults. N Engl J Med. 2023;388(12):1092-1100. PubMed
  175. Abtan J, Ducrocq G, Elbez Y, et al. Association between coffee or tea consumption and cardiovascular outcomes in patients with stable coronary artery disease: Analysis from the CLARIFY registry. Arch Cardiovasc Dis 2023;116(8-9):382-389. PubMed

See these in context on the Coffee monograph →

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

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

© 2021 Therapeutic Research Center, LLC

Keep exploring