Major interaction on record — check this product against your medications before combining. Based on 12 of 16 ingredients. Check your meds →
Dietary supplement

NRG Ingredients & Drug Interactions

by TLC Total Life Changes

Capsule Category: Other Combinations
Most serious interaction: Major
The interaction bottom line Most serious interaction: Major

NRG is a dietary supplement by TLC Total Life Changes with 16 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,558 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Tea ext, Bitter Orange ext, jet black Cocoa powder. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of NRG by TLC Total Life Changes

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

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 5 of its 16 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (738.80 mg) without saying how much of each component you get.

NRG contains 16 active ingredients. Vitamin B6 and vitamin B12 support energy metabolism and red blood cell formation.

Zinc aids immune function and wound healing. Magnesium supports muscle and nerve function.

Chromium and vanadium may help regulate blood glucose. Caffeine, green tea extract, and cocoa powder provide stimulant effects for mental alertness and energy.

Cinnamon, phenylethylamine, and bitter orange are included for their potential metabolic and mood-supporting properties. Three ingredients — alpha ketoglutaric acid, ConcenTrace AC, and Griffonia seed extract — we could not check for interactions.

The product also contains inactive ingredients: magnesium stearate, vegetarian capsule, and silica.

Does it work?

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

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

Why this rating?
  • The label markets this product for: enhance energy, burn fat, suppress appetite.
  • We looked for evidence on: Athletic performance, Attention, Metabolic rate, Thermogenesis, Satiety.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Caffeine is rated "Possibly Ineffective" for Attention deficit-hyperactivity disorder (ADHD).
  • Also on file: Magnesium is rated "Possibly Ineffective" for Athletic performance.

The effectiveness ratings in our data show vitamin B6 is effective for sideroblastic anemia and vitamin B6 deficiency, and likely effective for high homocysteine levels. Vitamin B12 is effective for B12 deficiency.

Zinc is effective for zinc deficiency and likely effective for Wilson disease. Magnesium is effective for constipation and low magnesium levels.

For the other active ingredients — chromium, vanadium, cinnamon, caffeine, green tea, phenylethylamine, cocoa, and bitter orange — the evidence we hold is either insufficient to establish effectiveness or shows possibly effective or possibly ineffective ratings for specific conditions. We have no effectiveness data on file for alpha ketoglutaric acid, ConcenTrace AC, or Griffonia seed extract.

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 12 of the 12 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 12 of 12.
  • General safety write-ups exist for 12 of 12.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Vitamin B6 is well tolerated at doses under 100 mg daily but can cause nerve damage (sensory neuropathy) at high doses over time. Vitamin B12 is generally very safe with no upper limit; it is needed in pregnancy and breastfeeding and considered safe at recommended amounts.

Zinc is well tolerated below 40 mg daily; higher doses may increase copper deficiency risk. Magnesium is generally well tolerated and safe in pregnancy at recommended amounts; the most common side effect is diarrhea.

Caffeine in moderate doses is generally safe for healthy adults but can cause anxiety, insomnia, and other stimulant effects; high amounts may carry pregnancy risks and pass into breast milk. Vanadium should be avoided in pregnancy and breastfeeding due to insufficient safety data, and high doses can damage the kidneys.

Chromium is usually well tolerated at typical doses but should be limited in pregnancy and breastfeeding. Cinnamon is likely safe in food amounts during pregnancy.

Green tea extract is generally well tolerated but concentrated extracts have rarely caused liver injury. Bitter orange should be avoided in pregnancy due to stimulant effects and lack of safety data.

Cocoa is generally safe in food amounts but contains caffeine and stimulants. Phenylethylamine should be avoided in pregnancy and breastfeeding due to lack of safety data.

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?
  • 12 of the 12 matched ingredients can interact with medications — Vanadium, Cocoa, Vitamin B12, Chromium, Vitamin B6, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,559 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 NRG, double-check if you take any of these: ephedrine (Major risk of dangerous stimulant effects with caffeine and green tea); nadolol or atorvastatin (Major reduction in drug levels from green tea); MAOIs or midazolam (Major interactions with bitter orange); blood pressure medications like antihypertensives (Moderate effect from vitamin B6 and cocoa); diabetes drugs (Moderate effect from vanadium, chromium, cinnamon, and bitter orange); seizure medications like phenobarbital, phenytoin, carbamazepine, valproate, ethosuximide, or felbamate (Moderate reduction in effectiveness); antibiotics including quinolones, tetracyclines, or cephalexin (Moderate interaction with zinc); levodopa/carbidopa (Major reduction in effectiveness); or HIV antiretrovirals (Moderate interactions with zinc). Altogether, these interactions span 1,536 individual medications.

Check your own medication Run your meds through the checker above

The bottom line

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

NRG is an energy and metabolism support product with 16 active ingredients. If you take any prescription medications — especially blood pressure drugs, diabetes medications, seizure medications, blood thinners, or HIV antiretrovirals — you should check your specific medications against the interactions listed on this page before starting.

The caffeine and stimulant content makes this product unsuitable for people with heart conditions, uncontrolled high blood pressure, or anxiety. Talk with your pharmacist before adding this to your routine.

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

Assessment coverage: 12 of 16 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Aug 23, 2019.

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 NRG, straight from the product label.

Brand TLC Total Life Changes
Net contents 30 Capsule(s)
Market status On market
Date entered into DSLD Aug 23, 2019
DSLD ID 206068
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for NRG by TLC Total Life Changes, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
15
IngredientAmount% DV
Vitamin B66 mg300%
Vitamin B12100 mcg1666.66%
Proprietary Blend738.8 mg--
Zinc2 mg13.33%
Vanadium0 NP--
Alpha Ketoglutaric Acid0 NP--
Chromium240 mcg200%
Cinnamon0 NP--
Phenylethylamine0 NP--
ConcenTrace AC0 NP--
Caffeine0 NP--
Magnesium9.8 mg2.4%
jet black Cocoa powder0 NP--
Green Tea ext0 NP--
Griffonia seed SE0 NP--
AquaMins0 NP--
Bitter Orange ext0 NP--

Other ingredients: Magnesium Stearate, Vegetarian Capsule, Silica

Tap any ingredient to jump to its full detail below.

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

Dietary Supplement

General Statements

Iaso Power on your energy

Enhance your energy, metabolize fat, and reduce hunger. The best-selling product provides an all-natural thermogenic blend that is designed to suppress your appetite so you can eat less food and not feel hungry.

TLC's best-selling dietary supplement provides an all-natural thermogenic blend of ingredients to enhance energy, burn fat, elevate mood, and suppress the appetite. NRG is designed to increase the body's metabolic rate and burn more fat. It is a safe alternative to unhealthy energy drinks (that may contain three to five-times the caffeine found in a twelve-ounce serving of coffee or soda).

Formula

Our unique formula includes leucine and green tea extracts. These natural ingredients can help prevent the body from converting calories into fat.

Active Ingredients Chromium Helps to transport blood sugar (glucose) from the bloodstream into cells where it is then used to convert fats, carbohydrates, and proteins into energy. Chromium also slows the body's loss of calcium. Vitamin B6 (Pyridoxine) Required for the proper processing of sugars, fats, and proteins in the body, vitamin B6 is also required for the proper growth and development of the brain, nerves, skin, and many other parts of the body. Vitamin B12 This vitamin is an essential water-soluble vitamin essential to the health of the brain, nerves, and skin. Up to 15% of adults have a vitamin B12 deficiency. Advantra Z (Citrus Aurantium) Widely known as bitter orange extract, Advantra Z is patented for fat burning (thermogensis). Advantra Z alters the way your body metabolizes fat, leading to weight loss. A study conducted at Georgetown University stated that Advantra Z may be, "the best thermogenic substitute for ephedra." Magnesium (Aquamin, Carbonate) Required for energy production and contributes to the structural development of bone, adults who consume less than the recommended amount of magnesium are more likely to have elevated inflammation markers. Zinc Needed for the proper growth and maintenance of the human body, this element is required for the proper immune system functions, wound healing, blood clotting, and the function of the thyroid. Beta-Phenethylamine A chemical naturally found in the body, Beta-Phenethylamine may improve athletic performance, speed weight loss, improve overall mood and increase the attention span. Green Tea Extract Made from the Camellia Sinensis plant, Green tea extract affects thinking and alertness, increases urine output, and may improve the function of the brain's chemical messengers. Epigallocatechin gallate (EGCG), a compound found in Green tea, is shown to increase fat oxidation by 33%. This 100%-pure extract may help to increase the body's metabolism, fat excretions, fat oxidation, and inhibit the development of fat cells.

Alpha-Ketoglutaric Acid (AKG) An organic acid that is important for the proper metabolism of all essential amino acids and the transfer of cellular energy in the citric acid cycle, AKG can reduce levels of ammonia formed in the brain, muscles, and kidneys. It may also help to balance the body's nitrogen chemistry and prevent nitrogen excess in body tissues and fluids. Individuals with high protein intake, bacterial infections, or gastrointestinal dysbiosis may benefit from supplemental AKG to help balance ammonia levels and protect tissues. Choline Bitartrate Choline is combined with a chemical salt (bitartrate) to help its absorption by the body. Small amounts of choline are naturally produced, but these amounts do not meet the requirements of the human body. This is one reason why supplementation is recommended. According to recent studies, the vast majority of peoples' diets lack the proper levels of this nutrient. It is estimated that 2% or fewer of all post-menopausal women receive enough choline bitartrate through food intake. 5-Hydroxytryptophan (5-HTP) Produced from the seeds of an African plant, Griffonia simplicifolia, 5-HTP increases the production of serotonin within the brain. Serotonin can affect sleep, appetite, body temperature, sexual behavior, and the sensation of pain. Since 5-HTP increases the synthesis of serotonin, it may play an important role in treating depression, insomnia, and obesity. Vanadyl Sulfate (Vanadium) A mineral used for improving athletic performance in weight training, Vanadium is believed to play a role in regulating the body's blood sugar levels in ways similar to insulin. Studies show that vanadyl sulfate helps muscle cells by increasing the levels of proteins, amino acids, and carbohydrates within the muscle tissues.

Suggested/Recommended/Usage/Directions

Iaso NRG should be taken daily on an empty stomach. Take one to two capsules with twenty-four ounces of water. Allow ninety minutes before digestion of breakfast or lunch.

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 diseases.

Precautions

This material is provided for informational purposes only and is not medical advice. Always consult your physician before beginning any new diet, exercise, or health regimen.

See for yourself

NRG by TLC Total Life Changes label

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

What’s inside

The Ingredients in NRG by TLC Total Life Changes

These are the 16 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container15 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
6 mg per serving Form: Pyridoxine Hydrochloride

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

Vitamin B6 monograph & interactions

Vitamin B12

Interacts with
20 drugs
100 mcg per serving Form: Cyanocobalamin

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

Vitamin B12 monograph & interactions

Proprietary Blend

738.8 mg per serving

Zinc

Interacts with
67 drugs
2 mg per serving Form: Zinc Gluconate

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but suppleme...

Zinc monograph & interactions

Chromium

Interacts with
178 drugs
240 mcg per serving Form: Chromium Niacinate

Chromium is an essential trace mineral involved in how the body handles sugar and fat. Some studies suggest it may modestly help blood sugar control i...

Chromium monograph & interactions

Magnesium

Interacts with
295 drugs
9.8 mg per serving Form: AquaMins, ConcenTrace AC, Magnesium Carbonate

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preven...

Magnesium monograph & interactions

Other (inactive) ingredients: Magnesium Stearate, Vegetarian Capsule, Silica. These complete the product’s ingredient list but are not active constituents.

Interaction report

NRG by TLC Total Life Changes Drug Interactions

Want to check YOUR meds against NRG?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

Go to the checker
1,558Drugs
29 Major 1,469 Moderate 60 Minor

Ingredients driving the most interactions

Caffeine 655
Cinnamon 442

Each ingredient & the kinds of drugs it affects

For each ingredient in NRG 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 Tea ext58 drug types · 1,293 drugs

Atorvastatin (Lipitor)

Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected. Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin. It is not clear if drinking green tea alters the absorption of atorvastatin.

Likelihood Likely Evidence B
Ephedrine

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

Likelihood Probable Evidence D
Nadolol (Corgard)

Green tea seems to reduce the levels and clinical effects of nadolol.
Preliminary clinical research shows that green tea consumption reduces plasma concentrations of nadolol. Compared to a control group, both peak levels and total drug exposure (AUC) of nadolol were reduced by approximately 85% in subjects who drank green tea daily for two weeks. Drinking green tea with nadolol also significantly reduced nadolol's systolic blood pressure lowering effect. Other clinical research shows that a single dose of green tea can affect plasma nadolol levels for at least one hour. Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is involved in the uptake of nadolol in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Likelihood Likely Evidence B
5-Fluorouracil

Theoretically, high doses of green tea might increase the effects and side effects of 5-fluorouracil.
Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425%.

Likelihood Possible Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup. Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea. However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity.

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Bortezomib (Velcade)

Theoretically, green tea might interfere with the effects of bortezomib.
In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines. Advise patients taking bortezomib, not to take green tea.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg. Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals.

Likelihood Possible Evidence D
Celiprolol (Celicard)

Theoretically, green tea might reduce the levels and clinical effects of celiprolol.
In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98%. This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Likelihood Possible Evidence D
Cimetidine (Tagamet)

Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.
Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels. Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine.

Likelihood Possible Evidence B
Contraceptive Drugs

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.
Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65%.

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

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

Likelihood Possible Evidence D
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, green tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Felbamate (Felbatol)

Theoretically, green tea might reduce the effects of felbamate and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Fexofenadine (Allegra)

Green tea can decrease blood levels of fexofenadine.
Clinical research shows that green tea can significantly decrease blood levels and excretion of fexofenadine. Taking green tea extract with a dose of fexofenadine decreased bioavailability of fexofenadine by about 30%. In vitro, green tea inhibits the cellular accumulation of fexofenadine by inhibiting the organic anion transporting polypeptide (OATP) drug transporter. Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates.

Likelihood Probable Evidence B
Flutamide (Eulexin)

Theoretically, green tea might increase the levels and adverse effects of flutamide.
Green tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk adverse effects.

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Hepatotoxic Drugs

Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Green tea extract supplements have been linked to several cases of hepatotoxicity and might have additive hepatotoxic effects with other drugs..

Likelihood Unlikely Evidence D
Imatinib (Gleevec)

Theoretically, green tea might reduce the levels and clinical effects of imatinib.
In animal research, a single dose of green tea extract reduces the area under the curve (AUC) of imatinib by up to approximately 64% and its main metabolite N-desmethyl imatinib by up to approximately 81%. This interaction has not been shown in humans. The mechanism of action is unclear but may involve multiple pathways.

Likelihood Possible Evidence D

Bitter Orange ext13 drug types · 957 drugs

Midazolam (Versed)

Bitter orange might increase blood levels of midazolam.
One small clinical study shows that bitter orange juice can increase midazolam levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4). Theoretically, bitter orange might increase the risk of midazolam-related adverse effects.

Likelihood Probable Evidence B
Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.
Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates.

Likelihood Probable Evidence D
Antidiabetes Drugs

Theoretically, bitter orange might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Some clinical research shows that drinking a tea containing bitter orange and Indian snakeroot reduces fasting and postprandial glucose levels in patients with type 2 diabetes who are using antidiabetes drugs. However, it is unclear if these effects are due to bitter orange, Indian snakeroot, or the combination. An animal study also shows that p-synephrine in combination with gliclazide , a sulfonylurea, causes an additional 20% to 44% decrease in glucose levels when compared with gliclazide alone.

Likelihood Possible Evidence B
Caffeine

Bitter orange might increase blood pressure and heart rate when taken with caffeine.
Small clinical studies show that taking bitter orange in combination with caffeine can increase blood pressure and heart rate in otherwise healthy normotensive adults. Theoretically, this might increase the risk of serious cardiovascular adverse effects.

Likelihood Possible Evidence B
Colchicine

Bitter orange might affect colchicine levels.
Colchicine is a substrate of P-glycoprotein and cytochrome P450 3A4 (CYP3A4). Bitter orange has been reported to inhibit CYP3A4 and increase levels of CYP3A4 substrates. However, one small clinical study in healthy adults shows that drinking bitter orange juice 240 mL twice daily for 4 days and taking a single dose of colchicine 0.6 mg on the 4th day decreases colchicine peak serum levels by 24%, time to peak serum level by 1 hour, and overall exposure to colchicine by 20%. The clinical significance of this finding is unclear.

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

Bitter orange might increase levels of drugs metabolized by CYP3A4.
Small clinical studies suggest that single or multiple doses of freshly squeezed bitter orange juice 200-240 mL can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. However, the extent of the effect of bitter orange on CYP3A4-mediated drug interactions is unknown. Some evidence suggests that bitter orange selectively inhibits intestinal CYP3A4, but not hepatic CYP3A4. Its effect on P-glycoprotein, which strongly overlaps with CYP3A4 interactions, is unclear. One small clinical study shows that drinking 8 ounces of freshly squeezed bitter orange juice has no effect on cyclosporine, which seems to be more dependent on hepatic CYP3A4 and P-glycoprotein than intestinal CYP3A4.

Likelihood Possible Evidence B
Dextromethorphan (Robitussin Dm, Others)

Bitter orange might increase blood levels of dextromethorphan.
One small clinical study shows that bitter orange juice increases dextromethorphan levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for dextromethorphan-related adverse effects.

Likelihood Possible Evidence B
Felodipine (Plendil)

Bitter orange might increase blood levels of felodipine.
One small clinical study shows that bitter orange juice increases felodipine levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for felodipine-related adverse effects.

Likelihood Probable Evidence B
Indinavir (Crixivan)

Bitter orange might increase blood levels of indinavir.
One small clinical study shows that bitter orange juice slightly increases indinavir levels, but this effect is likely to be clinically insignificant. Bitter orange selectively inhibits intestinal cytochrome P450 3A4 (CYP3A4); however, the metabolism of indinavir seems to be more dependent on hepatic CYP3A4. The effect of bitter orange on other protease inhibitors has not been studied.

Likelihood Possible Evidence B
Qt Interval-Prolonging Drugs

Theoretically, bitter orange might have an additive effect when combined with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.
One case report suggests that taking bitter orange in combination with other stimulants such as caffeine might prolong the QT interval in some patients.

Likelihood Possible Evidence D
Sildenafil (Viagra)

Bitter orange juice might increase blood levels of sildenafil.
A small clinical study in healthy adult males shows that drinking freshly squeezed bitter orange juice 250 mL daily for 3 days and taking a single dose of sildenafil 50 mg on the 3rd day increases the peak plasma concentration of sildenafil by 18% and the overall exposure to sildenafil by 44%. Theoretically, this may be due to inhibition of cytochrome P450 3A4 by bitter orange.

Likelihood Probable Evidence B
Stimulant Drugs

Theoretically, bitter orange might increase the risk of hypertension and adverse cardiovascular effects when taken with stimulant drugs.
Bitter orange appears to have stimulant effects.

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

Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.
In vitro research shows that octopamine, a constituent of bitter orange, weakly inhibits CYP2D6 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D

jet black Cocoa powder37 drug types · 661 drugs

Ace Inhibitors (Aceis)

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

Likelihood Possible Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Alcohol (Ethanol)

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Antihypertensive Drugs

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

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

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

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

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

Likelihood Possible Evidence D
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Ephedrine

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Flutamide (Eulexin)

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

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

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

Likelihood Possible Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenylpropanolamine

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

Likelihood Probable Evidence B
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Stimulant Drugs

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

Likelihood Probable Evidence C
Theophylline

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

Likelihood Probable Evidence B

Caffeine41 drug types · 655 drugs

Ephedrine

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

Likelihood Probable Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

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

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

Theoretically, caffeine might reduce the effects of carbamazepine and increase the risk for convulsions.
Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg. Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals.

Likelihood Possible Evidence D
Cimetidine (Tagamet)

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

Likelihood Likely Evidence B
Clozapine (Clozaril)

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

Likelihood Possible Evidence B
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

Theoretically, disulfiram use might increase the levels and adverse effects of caffeine.
Disulfiram decreases the rate of caffeine clearance.

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.
Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Felbamate (Felbatol)

Theoretically, caffeine might reduce the effects of felbamate and increase the risk for convulsions.
Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Flutamide (Eulexin)

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

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

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

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenylpropanolamine

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

Likelihood Probable Evidence B
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Pioglitazone (Actos)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D

Cinnamon2 drug types · 442 drugs

Antidiabetes Drugs

Theoretically, cassia cinnamon may have additive effects with antidiabetes drugs.
Cassia cinnamon may lower blood glucose levels, and have additive effects in patients treated with antidiabetic agents. Dose adjustments to diabetes medications might be necessary.

Likelihood Possible Evidence B
Hepatotoxic Drugs

Theoretically, large doses of cassia cinnamon might cause additive effects when used with hepatotoxic drugs.
There is some concern that ingesting large amounts of cassia cinnamon for an extended duration might cause hepatotoxicity in some people. Cassia cinnamon contains coumarin, which can cause hepatotoxicity in animal models. In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin use is discontinued. Lower amounts might also cause liver problems in sensitive people, such as those with liver disease or those taking potentially hepatotoxic agents.

Likelihood Possible Evidence D

Magnesium15 drug types · 295 drugs

Levodopa/Carbidopa (Sinemet)

Magnesium can reduce the bioavailability of levodopa/carbidopa.
Clinical research in healthy volunteers shows that taking magnesium oxide 1000 mg with levodopa 100 mg/carbidopa 10 mg reduces the area under the curve (AUC) of levodopa by 35% and of carbidopa by 81%. In vitro and animal research shows that magnesium produces an alkaline environment in the digestive tract, which might lead to degradation and reduced bioavailability of levodopa/carbidopa.

Likelihood Probable Evidence B
Aminoglycoside Antibiotics

Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
Both aminoglycosides and magnesium reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade and possible paralysis. This is most likely to occur with high doses of magnesium given intravenously.

Likelihood Possible Evidence D
Antacids

Use of acid reducers may reduce the laxative effect of magnesium oxide.
A retrospective analysis shows that, in the presence of H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs), a higher dose of magnesium oxide is needed for a laxative effect. This may also occur with antacids. Under acidic conditions, magnesium oxide is converted to magnesium chloride and then to magnesium bicarbonate, which has an osmotic laxative effect. By reducing acidity, antacids may reduce the conversion of magnesium oxide to the active bicarbonate salt.

Likelihood Possible Evidence D
Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Magnesium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after magnesium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Magnesium can decrease absorption of bisphosphonates.
Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours.

Likelihood Probable Evidence B
Calcium Channel Blockers

Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.
Magnesium inhibits calcium entry into smooth muscle cells and may therefore have additive effects with calcium channel blockers. Severe hypotension and neuromuscular blockades may occur when nifedipine is used with intravenous magnesium, although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness. High doses of magnesium could theoretically have additive effects with other calcium channel blockers.

Likelihood Possible Evidence D
Digoxin

Magnesium salts may reduce absorption of digoxin.
Clinical evidence suggests that treatment with oral magnesium hydroxide or magnesium trisilicate reduces absorption of digoxin from the intestines. This may reduce the blood levels of digoxin and decrease its therapeutic effects.

Likelihood Possible Evidence B
Potassium-Sparing Diuretics

Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.
Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics. Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.

Likelihood Probable Evidence D
Quinolone Antibiotics

Magnesium decreases absorption of quinolones.
Magnesium can form insoluble complexes with quinolones and decrease their absorption. Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects and accelerating the onset of effect.
Parenteral magnesium shortens the time to onset of skeletal muscle relaxants by about 1 minute and prolongs the duration of action by about 2 minutes. Magnesium potentiates the effects of skeletal muscle relaxants by decreasing calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes. Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate. A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg. Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time. It does not affect the activity of subsequently administered neostigmine.

Likelihood Probable Evidence A
Sulfonylureas

Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.
Clinical research shows that administration of magnesium hydroxide with glyburide increases glyburide absorption, increases maximal insulin response by 35-fold, and increases the risk of hypoglycemia, when compared with glyburide alone. A similar interaction occurs between magnesium hydroxide and glipizide. The mechanism of this effect appears to be related to the elevation of gastrointestinal pH by magnesium-based antacids, increasing solubility and enhancing absorption of sulfonylureas.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Magnesium decreases absorption of tetracyclines.
Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity. Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.
In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations. Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity. However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur.

Likelihood Unlikely Evidence B
Gabapentin (Neurontin)

Gabapentin absorption can be decreased by magnesium.
Clinical research shows that giving magnesium oxide orally along with gabapentin decreases the maximum plasma concentration of gabapentin by 33%, time to maximum concentration by 36%, and area under the curve by 43%. Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Unlikely Evidence B
Sevelamer (Renagel, Renvela)

Sevelamer may increase serum magnesium levels.
In patients on hemodialysis, sevelamer use was associated with a 0.28 mg/dL increase in serum magnesium. The mechanism of this interaction remains unclear.

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

Vanadium2 drug types · 208 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, vanadium might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
In vitro research shows that the sodium orthovanadate form of vanadium prolongs clotting time, likely through inhibition of thrombin and factor Xa.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, vanadium might increase the risk of hypoglycemia when taken with antidiabetes drugs.
A few very small clinical studies in patients with type 2 diabetes show that the vanadyl sulfate form of vanadium increases insulin sensitivity and might lower blood glucose levels.

Likelihood Probable Evidence B

Phenylethylamine2 drug types · 187 drugs

Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking phenethylamine concomitantly with MAOIs may increase adverse effects.
In humans, phenethylamine is oxidized by MAO-B to form the inactive metabolite phenylacetic acid. Animal research shows that administering an MAOI prior to phenethylamine increases the amphetamine-like effects of phenethylamine. However, low-quality clinical research has used phenethylamine with selegiline, an MAOI, with apparent safety.

Likelihood Possible Evidence D
Serotonergic Drugs

Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of serotonergic adverse effects.
Animal research shows that phenethylamine increases levels of serotonin, norepinephrine, and dopamine. Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of additive serotonergic adverse effects, including serotonin syndrome and cerebral vasoconstrictive disorders. However, low-quality clinical research has used phenethylamine with selegiline, a monoamine oxidase inhibitor (MAOI), with apparent safety.

Likelihood Possible Evidence D

Chromium5 drug types · 178 drugs

Antidiabetes Drugs

Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
Some research shows that taking chromium might lower blood glucose levels, especially in patients with poorly controlled type 2 diabetes.

Likelihood Possible Evidence A
Insulin

Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
In clinical research, chromium has been shown to increase insulin sensitivity,

Likelihood Possible Evidence B
Levothyroxine (Synthroid, Others)

Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone. Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.

Likelihood Probable Evidence B
Aspirin

Theoretically, aspirin might increase chromium absorption.
Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood.

Likelihood Possible Evidence D
Nonsteroidal Anti-Inflammatory Drugs (Nsaids)

NSAIDs might increase chromium levels in the body.
Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention.

Likelihood Possible Evidence D

Zinc10 drug types · 67 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Theoretically, zinc might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after zinc containing products.

Likelihood Probable Evidence D
Cephalexin (Keflex)

Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.
A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose. To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.

Likelihood Probable Evidence B
Cisplatin (Platinol-Aq)

Theoretically, zinc might interfere with the therapeutic effects of cisplatin.
Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin. It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.

Likelihood Possible Evidence D
Integrase Inhibitors

Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Zinc is a divalent cation. Pharmacokinetic studies have shown that other divalent cations such as calcium and iron can decrease blood levels of the integrase inhibitor dolutegravir through chelation.

Likelihood Possible Evidence D
Penicillamine (Cuprimine, Depen)

Zinc might reduce the levels and clinical effects of penicillamine.
By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated. Advise patients to take zinc and penicillamine at least 2 hours apart.

Likelihood Probable Evidence B
Quinolone Antibiotics

Zinc can decrease the levels and clinical effects of quinolones antibiotics.
Quinolones form complexes with zinc in the gastrointestinal tract, reducing absorption of both the quinolone and zinc if taken at the same time. Advise patients to take these drugs at least 2 hours before, or 4-6 hours after, zinc supplements.

Likelihood Probable Evidence B
Ritonavir (Norvir)

Zinc modestly reduces levels of ritonavir.
Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption. In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16%. However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Zinc might reduce levels of tetracycline antibiotics.
Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time. Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40%. Demeclocycline and minocycline cause a similar interaction. However, doxycycline does not seem to interact significantly with zinc. Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.

Likelihood Probable Evidence B
Amiloride (Midamor)

Amiloride can modestly reduce zinc excretion and increase zinc levels.
Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses. The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.

Likelihood Probable Evidence B
Atazanavir (Reyataz)

Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.
Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption. Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication.

Likelihood Probable Evidence B

Vitamin B121 drug type · 20 drugs

Metformin (Glucophage)

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

Likelihood Possible Evidence A
The maker

Brand information

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

TLC Total Life Changes

See all TLC Total Life Changes products
Name
Total Life Changes
Pharmacist Counseling Corner

NRG by TLC Total Life Changes: Common Questions

Does NRG by TLC Total Life Changes interact with any medications?
Yes. Based on its ingredients, NRG has a known interaction with 1,558 medications, including 29 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
NRG contains 16 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.
Can I take NRG if I'm pregnant?
Several ingredients in this product carry concerns in pregnancy. Vanadium should be avoided due to lack of safety data. Chromium safety data is limited, so extra supplement doses should be avoided unless your doctor approves. Cinnamon is likely safe in food amounts. Caffeine is present in high amounts, and your doctor should advise on safe limits. Talk with your obstetrician before taking this product.
Can I take NRG while breastfeeding?
Caffeine, green tea, and cocoa all pass into breast milk and may affect your baby. Vanadium should be avoided due to insufficient safety data. Vitamin B12 is actually needed while breastfeeding and is safe at recommended amounts. If you want to breastfeed, discuss this product with your doctor or pharmacist first.
What does the caffeine in NRG do?
Caffeine is effective for mental alertness and athletic performance. It's also used clinically for neonatal apnea. In this product, it works alongside other stimulants like green tea and cocoa to boost energy and focus. Be aware it can cause anxiety, insomnia, and dependence with chronic use.
Will NRG help me lose weight or boost my metabolism?
The ingredients we have effectiveness data for — chromium, vanadium, cinnamon, and bitter orange — show either insufficient evidence or mixed results for weight loss and metabolism. Phenylethylamine has insufficient evidence for obesity. The stimulant ingredients may increase energy expenditure, but the evidence for actual weight loss is not established in our data.
Is it safe to take NRG every day?
Daily use depends on your health and medications. Caffeine can cause dependence with chronic use. Vitamin B6 at high cumulative doses can cause nerve damage. Vanadium at high doses can damage the kidneys. If you're healthy and not taking medications, moderate daily use may be tolerable, but run your medications through the checker on this page first and talk with your pharmacist about your routine.
What are the most common side effects of NRG?
The most common side effects come from the stimulants: anxiety, restlessness, insomnia, headache, nausea, and tremors from caffeine; and gastrointestinal effects (nausea, stomach upset, diarrhea) from magnesium and other ingredients. At higher doses or in sensitive people, you may also experience elevated heart rate or blood pressure.

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

Not sure if NRG 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.

NRG label
Go deeper

The Full Monographs Behind NRG’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

Vitamin B12

Interacts with 20 drugs

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

Read the full Vitamin B12 monograph →
Herb & supplement monograph

Vanadium

Interacts with 208 drugs

Vanadium is a trace mineral found in tiny amounts in food, and people get plenty from a normal diet. Supplement claims for diabetes, weight, and athletic performance are not well proven, and...

Read the full Vanadium monograph →
Herb & supplement monograph

Cassia Cinnamon

Interacts with 442 drugs

Cassia cinnamon is the common, inexpensive cinnamon used in cooking, and it is also taken as a supplement, most often for blood sugar support. The evidence for its health benefits is mixed a...

Read the full Cassia Cinnamon monograph →
Herb & supplement monograph

Phenethylamine (pea)

Interacts with 187 drugs

Phenethylamine (PEA) is a natural compound made in the body and found in foods like chocolate; supplements are marketed for mood, focus, and energy. Reliable human research on the supplement...

Read the full Phenethylamine (pea) monograph →
Herb & supplement monograph

Caffeine

Interacts with 655 drugs

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

Read the full Caffeine monograph →
Herb & supplement monograph

Cocoa

Interacts with 661 drugs

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

Read the full Cocoa monograph →
Herb & supplement monograph

Green Tea

Interacts with 1,293 drugs

Green tea is a popular beverage rich in antioxidants called catechins, and drinking it in normal amounts is considered safe for most people. Concentrated green tea extracts are a different s...

Read the full Green Tea monograph →
Herb & supplement monograph

Bitter Orange

Interacts with 957 drugs

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance i...

Read the full Bitter Orange monograph →
Herb & supplement monograph

Zinc

Interacts with 67 drugs

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but supplements can help correct or prevent a defici...

Read the full Zinc monograph →
Herb & supplement monograph

Chromium

Interacts with 178 drugs

Chromium is an essential trace mineral involved in how the body handles sugar and fat. Some studies suggest it may modestly help blood sugar control in certain people with type 2 diabetes, b...

Read the full Chromium monograph →
Herb & supplement monograph

Magnesium

Interacts with 295 drugs

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preventing or correcting deficiency. Some othe...

Read the full Magnesium monograph →
Sources

Sources & How We Checked

NRG'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 950 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.

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

See these in context on the Vitamin B6 monograph →

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

See these in context on the Vitamin B12 monograph →

Zinc 88 references
  1. Barceloux DG. Zinc. J Toxicol Clin Toxicol 1999;37:279-92.
  2. Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984;25:20-4. DOI
  3. Smith DS, Helzner EC, Nuttall CE Jr, et al. Failure of zinc gluconate in treatment of acute upper respiratory tract infections. Antimicrob Agents Chemother 1989;33:646-8. PubMed
  4. Blondeau JM. Expanded activity and utility of the new fluoroquinolones: a review. Clin Ther 1999;21:3-40. PubMed
  5. Reyes AJ, Olhaberry JV, Leary WP, et al. Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J 1983;64:936-41.
  6. Kugelmas M. Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 2000;19:13-5. PubMed
  7. Hebel SK, ed. Drug Facts and Comparisons. 52nd ed. St. Louis: Facts and Comparisons, 1998.
  8. Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med 1998;18:673-85. DOI
  9. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, et al. Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. PubMed
  10. Fosmire GJ. Zinc toxicity. Am J Clin Nutr 1990;51:225-7.
  11. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. PubMed
  12. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  13. Seelig MS. Auto-immune complications of D-penicillamine - A possible result of zinc and magnesium depletion and of pyridoxine inactivation. J Am Coll Nutr 1982;1:207-14. PubMed
  14. Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs 1976;11:45-54.. PubMed
  15. Hirt M, Nobel S, Barron E. Zinc nasal gel for the treatment of common cold symptoms: A double-blind, placebo-controlled trial. Ear Nose Throat J 2000;79:778-82.. DOI
  16. Simkin PA. Oral zinc sulphate in rheumatoid arthritis. Lancet 1976;2:539-42. PubMed
  17. Wray D. A double-blind trial of systemic zinc sulfate in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982;53:469-72. PubMed
  18. Douglas RM, Miles HB, Moore BW, et al. Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract infections in Australian adults. Antimicrob Agents Chemother 1987;31:1263-5. PubMed
  19. Lagiou P, Wuu J, Trichopoulou A, et al. Diet and benign prostatic hyperplasia: a study in Greece. Urology 1999;54:284-90. PubMed
  20. Ewing CI, Gibbs AC, Ashcroft C, David TJ. Failure of oral zinc supplementation in atopic eczema. Eur J Clin Nutr 1991;45:507-10.
  21. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  22. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. AREDS report no. 8. Arch Oph
  23. Greenberg JE, Lynn M, Kirsner RS, et al. Mucocutaneous pigmented macule as a result of zinc deposition. J Cutan Pathol 2002;29:613-5. PubMed
  24. Godfrey HR, Godfrey NJ, Godfrey JC, Riley D. A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med 2001;7:49-56.
  25. Turner RB. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis 2001;33:1865-70. PubMed
  26. Belongia EA, Berg R, Liu K. A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults. Am J Med 2001;111:103-8. PubMed
  27. Mossad SB. Effect of zincum gluconicum nasal gel on the duration and symptom severity of the common cold in otherwise healthy adults. QJM 2003;96:35-43. DOI
  28. Leitzmann MF, Stampfer MJ, Wu K, et al. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst 2003;95:1004-7.. PubMed
  29. Jafek BW, Linschoten M, Murrow BW. Zicam Induced Anosmia. American Rhinologic Society 49th Annual Fall Scientific Meeting abstract. Orlando, Florida. September 20, 2003. http://app.american-rhinologic.org/programs/2003ARSFallProgram071503.pdf (Accessed 24
  30. Uebayashi H, Hatanaka T, Kanemura F, Tonosaki K. Acute anosmia in the mouse: behavioral discrimination among the four basic taste substances. Physiol Behav 2001;72:291-6.. PubMed
  31. Barrett S. Zicam Marketers Sued. United States District Court Western District of Michigan Southern Division, Filed October 14, 2003, Case No. 4:03CV0146.
  32. Bilici M, Yildirim F, Kandil S, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:181-90.. PubMed
  33. Polk RE, Healy DP, Sahai J, et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother 1989;33:1841-4. PubMed
  34. Mery C, Delrieu F, Ghozlan R, et al. Controlled trial of D-penicillamine in rheumatoid arthritis. Dose effect and the role of zinc. Scand J Rheumatol 1976;5:241-7. PubMed
  35. Penttila O, Hurme H, Neuvonen PJ. Effect of zinc sulfate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4.
  36. Kondo Y, Yamagata K, Satoh M, et al. Optimal administration schedule of cisplatin for bladder tumor with minimal induction of metallothionein. J Urol 2003;170:2467-70. PubMed
  37. Doz F, Berens ME, Deschepper CF, et al. Experimental basis for increasing the therapeutic index of cis-diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high-zinc diet. Cancer Chemother Pharmacol 1992;29:219-26.
  38. Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12. PubMed
  39. Golik A, Modai D, Weissgarten J, et al. Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion. Clin Pharmacol Ther 1987;42:42-4. PubMed
  40. Leary WP, Reyes AJ, Van der Byl K. Urinary magnesium and zinc excretion after two different single doses of amiloride in healthy adults. Curr Ther Res 1983;34:205-16.
  41. McBride K, Slotnick B, Margolis FL. Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study. Chem Senses 2003;28:659-70. PubMed
  42. Burd GD. Morphological study of the effects of intranasal zinc sulfate irrigation on the mouse olfactory epithelium and olfactory bulb. Microsc Res Tech 1993;24:195-213. PubMed
  43. Ducray A, Bondier JR, Michel G, et al. Recovery following peripheral destruction of olfactory neurons in young and adult mice. Eur J Neurosci 2002;15:1907-17. PubMed
  44. Mayer AD, Rosenblatt JS. Peripheral olfactory deafferentation of the primary olfactory system in rats using ZnSO4 nasal spray with special reference to maternal behavior. Physiol Behav 1993;53:587-92. PubMed
  45. DeCook CA, Hirsch AR. Anosmia due to inhalational zinc: a case report (abstract). Chem Senses 2000;25:659.
  46. Tisdall FF, Brown A, Defries RD. Persistent anosmia following zinc sulfate nasal spraying. JPed 1938;18:60-2. DOI
  47. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64. PubMed
  48. Public Health Advisory. Loss of sense of smell with intranasal cold remedies containing zinc. U.S. Food and Drug Administration, June 16, 2009. Available at: http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm166059.htm (Accessed 16 June 2009)
  49. Dooren JC. FDA warns against use of Zicam. The Wall Street Journal, June 16, 2009. Available at: http://online.wsj.com/article/SB124516778692319231.html#mod=djemHL?mg=com-wsj (Accessed 16 June 2009).
  50. Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced anosmia syndrome. Laryngoscope 2006;116:217-20.
  51. Health Canada / GlaxoSmithKline Consumer Healthcare. Association of long-term, excessive use of zinc-containing Poli-Grip products with myeloneuropathy and blood dyscrasias. February 18, 2010. Available at: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medef
  52. GlaxoSmithKline Consumer Advisory. GlaxoSmithKline (GSK) warns about a potential health risk associated with long-term, excessive use of GSK's zinc-containing denture adhesives Super Polygrip Original, Ultra Fresh and Extra Care. February 18, 2010. Availa
  53. Science M, Johnstone J, Roth DE, et al. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 2012;184:E551-61. PubMed
  54. Castilla-Higuero, L., Romero-Gomez, M., Suarez, E., and Castro, M. Acute hepatitis after starting zinc therapy in a patient with presymptomatic Wilson's disease. Hepatology 2000;32(4 Pt 1):877. PubMed
  55. Sharquie, K. E., Najim, R. A., Farjou, I. B., and Al Timimi, D. J. Oral zinc sulphate in the treatment of acute cutaneous leishmaniasis. Clin.Exp.Dermatol. 2001;26(1):21-26. PubMed
  56. Dreno, B., Moyse, D., Alirezai, M., Amblard, P., Auffret, N., Beylot, C., Bodokh, I., Chivot, M., Daniel, F., Humbert, P., Meynadier, J., and Poli, F. Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of
  57. Moore, R. Bleeding gastric erosion after oral zinc sulphate. Br.Med J 3-25-1978;1(6115):754. PubMed
  58. Jafek, B. W., Linschoten, M. R., and Murrow, B. W. Anosmia after intranasal zinc gluconate use. Am J Rhinol. 2004;18(3):137-141. DOI
  59. Simonart, T. and de, Maertelaer, V. Systemic treatments for cutaneous warts: a systematic review. J Dermatolog.Treat. 2012;23(1):72-77. PubMed
  60. Cochran, R. J., Tucker, S. B., and Flannigan, S. A. Topical zinc therapy for acne vulgaris. Int.J Dermatol. 1985;24(3):188-190. DOI
  61. Morgan, A. A. Bleeding gastric erosion after oral zinc sulphate. Br.Med.J. 5-13-1978;1(6122):1283-1284. PubMed
  62. Murphy, J. V. Intoxication following ingestion of elemental zinc. JAMA 6-22-1970;212(12):2119-2120.
  63. Lang, C. J., Rabas-Kolominsky, P., Engelhardt, A., Kobras, G., and Konig, H. J. Fatal deterioration of Wilson's disease after institution of oral zinc therapy. Arch Neurol. 1993;50(10):1007-1008. PubMed
  64. Fjellner, B. Drug-induced lupus erythematosus aggravated by oral zinc therapy. Acta Derm.Venereol. 1979;59(4):368-370. DOI
  65. Varas Lorenzo, M. J. Zinc acexamate and ranitidine in the short- and mid-term management of gastroduodenal ulcers. Curr Ther Res 21986;39:19-29.
  66. Bosch, F. and Jimenez, E. Post-marketing surveillance of zinc acexamate in peptic ulcer treatment. Clin Trials J 1990;27:301-312.
  67. DeCook, C. A. and Hirsch, A. R. Anosmia due to inhalational zinc: a case report (abstract). Chem Senses 2000;25:659.
  68. Crown LA, May JA. Zinc toxicity: denture adhesives, bone marrow failure and polyneuropathy. Tenn Med. 2012 Feb;105(2):39-40, 42.
  69. Dadamio J, Van Tournout M, Teughels W, Dekeyser C, Coucke W, Quirynen M. Efficacy of different mouthrinse formulations in reducing oral malodour: a randomized clinical trial. J Clin Periodontol. 2013 May;40(5):505-13. PubMed
  70. Moyle G, Else L, Jackson A, Back D, Yapa MH, Seymour N, Ringner-Nackter L, Karolia Z, Gazzard B, Boffito M. Coadministration of atazanavir-ritonavir and zinc sulfate: impact on hyperbilirubinemia and pharmacokinetics. Antimicrob Agents Chemother. 2013 Aug PubMed
  71. Zittel S, Ufer F, Gerloff C, Münchau A, Rosenkranz M. Severe myelopathy after denture cream use--is copper deficiency or excess zinc the cause? Clin Neurol Neurosurg. 2014 Jun;121:17-8. PubMed
  72. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  73. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Drug Interactions between Integrase Inhibitors and Other Drugs. AIDSinfo. July 14, 2016. Available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescen
  74. Ding Y, Jia YY, Li F, et al. The effect of staggered administration of zinc sulfate on the pharmacokinetics of oral cephalexin. Br J Clin Pharmacol. 2012 Mar;73(3):422-7. PubMed
  75. Fallah R, Sabbaghzadegan S, Karbasi SA, Binesh F. Efficacy of zinc sulfate supplement on febrile seizure recurrence prevention in children with normal serum zinc level: A randomised clinical trial. Nutrition. 2015;31(11-12):1358-61. PubMed
  76. Lazzerini M, Wanzira H. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2016;12:CD005436. PubMed
  77. Mahmoud AM, Al-Alem U, Dabbous F, et al. Zinc intake and risk of prostate cancer: Case-control study and meta-analysis. PLoS One. 2016;11(11):e0165956. PubMed
  78. Nagraj SK, George RP, Shetty N, Levenson D, Ferraiolo DM, Shrestha A. Interventions for managing taste disturbances. Cochrane Database Syst Rev. 2017 Dec 20;12(12):CD010470. PubMed
  79. Yee BE, Richards P, Sui JY, Marsch AF. Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatol Ther. 2020:e14252. PubMed
  80. Janyajirawong R, Vilaichone RK, Sethasine S. Efficacy of zinc supplement in minimal hepatic encephalopathy: A prospective, randomized controlled study (Zinc-MHE Trial). Asian Pac J Cancer Prev 2021;22(9):2879-2887. PubMed
  81. Nakano M, Nakamura Y, Miyazaki A, Takahashi J. Zinc pharmacotherapy for elderly osteoporotic patients with zinc deficiency in a clinical setting. Nutrients 2021;13(6):1814. PubMed
  82. Tolino E, Skroza N, Mambrin A, et al. An open-label study comparing oral zinc to lymecycline in the treatment of acne vulgaris. J Clin Aesthet Dermatol 2021;14(5):56-58.
  83. Hunter J, Arentz S, Goldenberg J, et al. Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2021;11(11):e047474. PubMed
  84. Yamazaki K, Kageyama H, Fujiyama T, Ito T, Urano S, Honda T. A case of systemic contact dermatitis due to zinc supplements. Int J Dermatol 2022. PubMed
  85. Magham K, Han J, Eilbert W, Bunney EB. Severe copper deficiency anemia caused by zinc supplement use. Am J Emerg Med 2023;72:222. PubMed
  86. Sivakumar RR, Chinnaiah Govindareddy D, Sahoo J, Bobby Z, Chinnakali P. Effect of daily zinc supplementation for 12 weeks on serum thyroid auto-antibody levels in children and adolescents with autoimmune thyroiditis - a randomized controlled trial. J Pedi PubMed
  87. AlDhasee O, AlMalki H, AlKharashi N, AlJeraisy N, Al Deeb M. Acute zinc sulfate overdose: clinical presentation and management. BMJ Case Rep 2025;18(1):e263899. PubMed
  88. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Zinc monograph →

Vanadium 15 references
  1. Harland BF, Harden-Williams BA. Is vanadium of human nutritional importance yet? J Am Diet Assoc 1994;94:891-4. PubMed
  2. Sitprija V, Tungsanga K, Tosukhowong P, et al. Metabolic problems in northeastern Thailand: possible role of vanadium. Mineral Electrolyte Metab 1998;19:51-6.
  3. Funakoshi T, Shimada H, Kojima S, et al. Anticoagulant action of vanadate. Chem Pharmaceut Bull 1992;40:174-6. PubMed
  4. Halberstam M, Cohen N, Shlimovich P, et al. Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects. Diabetes 1996;45:659-66. PubMed
  5. Cohen N, Halberstam M, Shlimovich P, et al. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1995;95:2501-9. PubMed
  6. Boden G, Chen X, Ruiz J, et al. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism 1996;45:1130-5.
  7. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  8. Goldfine AB, Simonson DC, Folli F, et al. Metabolic effects of sodium metavanadate in humans with insulin-dependent and noninsulin-dependent diabetes mellitus in vivo and in vitro studies. J Clin Endocrinol Metab 1995;80:3311-20. PubMed
  9. Cusi K, Cukier S, DeFronzo RA, et al. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab 2001;86:1410-7.
  10. Peat F, Coomber R, Rana A, Vince A. Vanadium allergy following total knee arthroplasty. BMJ Case Rep 2018;2018. pii: bcr-2017-222092. doi: 10.1136/bcr-2017-222092. PubMed
  11. Jin S, Xia W, Jiang Y, et al. Urinary vanadium concentration in relation to premature rupture of membranes: A birth cohort study. Chemosphere 2018;210:1035-41. doi: 10.1016/j.chemosphere.2018.07.110. PubMed
  12. Garcia-Nunez I, Algaba-Marmol MA, Suarez-Vergara M, et al. Vanadium contact dermatitis: case report and studies performed. Contact Dermatitis 2019;80(2):127-8. PubMed
  13. Zhou Y, Zhu Q, Ma W, et al. Prenatal vanadium exposure, cytokine expression, and fetal growth: a gender-specific analysis in Shanghai MCPC study. Sci Total Environ 2019;685:1152-9. PubMed
  14. Jiang S, Zhou S, Liu H, et al. Concentrations of vanadium in urine with hypertension prevalence and blood pressure levels. Ecotoxicol Environ Saf 2021;213:112028. PubMed
  15. Zhang W, Chen H, Zeng Q, Xu S, Xia W, Li Y. Prenatal and postnatal exposure to vanadium and the immune function of children. J Trace Elem Med Biol 2021;67:126787. PubMed

See these in context on the Vanadium monograph →

Chromium 53 references
  1. Cerulli J, Grabe DW, Gauthier I, et al. Chromium picolinate toxicity. Ann Pharmacother 1998;32:428-31. PubMed
  2. Urberg M, Zemel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabolism 1987;36:896-9. PubMed
  3. Mohamedshah FY, Moser-Veillon PB, Yamini S, et al. Distribution of a stable isotope of chromium (53Cr) in serum, urine, and breast milk in lactating women. Am J Clin Nutr 1998;67:1250-5. PubMed
  4. Wasser WG, Feldman NS, D'Agati VD. Chronic renal failure after ingestion of over-the-counter chromium picolinate. [letter]. Ann Intern Med 1997;126:410. PubMed
  5. Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998;56:174-7. PubMed
  6. Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 1998;17:548-55. PubMed
  7. McLeod MN, Gaynes BN, Golden RN. Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients. J Clin Psych 1999;60:237-40. PubMed
  8. Fowler JF Jr. Systemic contact dermatitis caused by oral chromium picolinate. Cutis 2000;65:116. DOI
  9. Trent LK, Thieding-Cancel D. Effects of chromium picolinate on body composition. J Sports Med Phys Fitness 1995;35:273-80.
  10. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  11. Rabinovitz H, Friedensohn A, Leibovitz A, et al. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004;74:178-82. PubMed
  12. Lanca S, Alves A, Vieira AI, et al. Chromium-induced toxic hepatitis. Eur J Intern Med 2002;13:518-20. PubMed
  13. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  14. Davidson JR, Abraham K, Connor KM, McLeod MN. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53:261-4.. PubMed
  15. Food Standards Agency. Medicines and Healthcare products Regulatory Agency (MHRA). Expert Group on Vitamins and Minerals. Available at: http://cot.food.gov.uk/sites/default/files/vitmin2003.pdf.
  16. Mouser JF, Hak EB, Helms RA, et al. Chromium and zinc concentrations in pediatric patients receiving long-term parenteral nutrition. Am J Health Syst Pharm 1999;56:1950-6. PubMed
  17. Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med 2005;142:477-8. PubMed
  18. Wani S, Weskamp C, Marple J, Spry L. Acute tubular necrosis associated with chromium picolinate-containing dietary supplement. Ann Pharmacother 2006;40:563-6. PubMed
  19. Kleefstra N, Houweling ST, Jansman FG, et al. Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care 2006;29: PubMed
  20. Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006;29:1826-32. PubMed
  21. Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther 2006;8:636-43. PubMed
  22. John-Kalarickal J, Pearlman G, Carlson HE. New medications which decrease levothyroxine absorption. Thyroid 2007;17:763-5. PubMed
  23. Yazaki Y, Faridi Z, Ma Y, et al. A pilot study of chromium picolinate for weight loss. J Altern Complement Med 2010;16:291-9. PubMed
  24. Davis ML, Seaborn CD, and Stoecker BJ. Effects of over-the-counter drugs on chromium retention and urinary excretion in rats. Nutrition Research 1995;15(2):201-210.
  25. Young P, Turiansky G, Bonner M, and et al. Acute generalized exanthematous pustulosis induced by chromium picolinate. J.Am Acad.Dermatol. 1999;41(5 Pt 2):820-823. PubMed
  26. Gibb, H. J., Lees, P. S., Pinsky, P. F., and Rooney, B. C. Lung cancer among workers in chromium chemical production. Am J Ind.Med 2000;38(2):115-126. DOI
  27. Gibb, H. J., Lees, P. S., Pinsky, P. F., and Rooney, B. C. Clinical findings of irritation among chromium chemical production workers. Am J Ind.Med 2000;38(2):127-131. PubMed
  28. Pittler, M. H. and Ernst, E. Dietary supplements for body-weight reduction: a systematic review. Am.J.Clin Nutr. 2004;79(4):529-536. PubMed
  29. Pei, D., Hsieh, C. H., Hung, Y. J., Li, J. C., Lee, C. H., and Kuo, S. W. The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism 2 PubMed
  30. Hisatomi, K., Ishii, H., Hashiguchi, K., Seki, M., Ide, M., Sugiyama, K., Ishimoto, H., Nakayama, S., Mukae, H., and Kohno, S. Interstitial pneumonia caused by inhalation of fumes of nickel and chrome. Respirology. 2006;11(6):814-817. PubMed
  31. Kleefstra, N., Houweling, S. T., Bakker, S. J., Verhoeven, S., Gans, R. O., Meyboom-de Jong, B., and Bilo, H. J. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled tri DOI
  32. Parsons, A., Ingram, J., Inglis, J., Aveyard, P., Johnstone, E., Brown, K., Franklin, M., and Bermudez, I. A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to pr
  33. Bagdon RE and Hazen RE. Skin permeation and cutaneous hypersensitivity as a basis for making risk assessments of chromium as a soil contaminant. Environ.Health Perspect. 1991;92:111-119. PubMed
  34. Bharmal, S. V., Moyes, V., Ahmed, S., and Grossman, A. Hypoglycaemia: possible mediation by chromium salt medication. Hormones.(Athens.) 2010;9(2):181-183. PubMed
  35. Krol, E., Krejpcio, Z., Byks, H., Bogdanski, P., and Pupek-Musialik, D. Effects of chromium brewer's yeast supplementation on body mass, blood carbohydrates, and lipids and minerals in type 2 diabetic patients. Biol.Trace Elem.Res. 2011;143(2):726-737.
  36. Unisa, S., Jagannath, P., Dhir, V., Khandelwal, C., Sarangi, L., and Roy, T. K. Population-based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North India. HPB (Oxford) 2011;13(2):117-125. PubMed
  37. Noda, S., Asano, Y., and Sato, S. Lichen planus in a patient with long-term exposure to chrome. Eur.J.Dermatol. 2011;21(3):417-418. PubMed
  38. Xiang, J., Sun, Z., and Huan, J. N. Intensive chromic acid burns and acute chromium poisoning with acute renal failure. Chin Med.J.(Engl.) 7-5-2011;124(13):2071-2073.
  39. Chhabra, D., Oda, K., Jagannath, P., Utsunomiya, H., Takekoshi, S., and Nimura, Y. Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan. Asian Pac.J.Cancer Prev. 2012;13(1):187-190. PubMed
  40. Huszonek, J. Over-the-counter chromium picolinate. Am J Psychiatry 1993;150(10):1560-1561. PubMed
  41. Bunner S and McGinnis R. Chromium-induced hypoglycemia. Psychosomatics 1998;39(3):298-299. PubMed
  42. Martin, W. R. and Fuller, R. E. Suspected chromium picolinate-induced rhabdomyolysis. Pharmacotherapy 1998;18(4):860-862. DOI
  43. Proctor, D. M., Fredrick, M. M., Scott, P. K., Paustenbach, D. J., and Finley, B. L. The prevalence of chromium allergy in the United States and its implications for setting soil cleanup: a cost-effectiveness case study. Regul.Toxicol Pharmacol 1998;28(1 PubMed
  44. De Marchi S, Cecchin E, De Marchi SU. Systemic allergic dermatitis resulting from oral administration of chromium with a food supplement. Contact Dermatitis 2014;70(2):123-5. PubMed
  45. Hedberg YS, Gumulka M, Lind ML, Matura M, Lidén C. Severe occupational chromium allergy despite cement legislation. Contact Dermatitis. 2014;70(5):321-3. PubMed
  46. Thyssen JP, Jellesen MS, Møller P, Menné T, Johansen JD. Allergic chromium dermatitis from wearing 'chromium-free' footwear. Contact Dermatitis 2014;70(3):185-7. PubMed
  47. Liu Y, Cotillard A, Vatier C, et al. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial. PLoS One.
  48. Jamilian M, Asemi Z. Chromium Supplementation and the Effects on Metabolic Status in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Nutr Metab. 2015;67(1):42-8. PubMed
  49. Guimarães MM, Carvalho AC, Silva MS. Effect of chromium supplementation on the glucose homeostasis and anthropometry of type 2 diabetic patients: Double blind, randomized clinical trial: Chromium, glucose homeostasis and anthropometry. J Trace Elem Med Bi PubMed
  50. Paiva AN, Lima JG, Medeiros AC, et al. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Elem Med Biol. 2015;32:66-72. PubMed
  51. Yin RV, Phung OJ. Effect of chromium supplementation on glycated hemoglobin and fasting plasma glucose in patients with diabetes mellitus. Nutr J. 2015;14:14. PubMed
  52. Jamilian M, Zadeh Modarres S, Amiri Siavashani M, et al. The influences of chromium supplementation on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome women candidate for in vitro fertilizati
  53. Alinaghi F, Thyssen JP, Zachariae C, Johansen JD. No immediate effect of regulatory reduction of chromium in leather among adult patients with chromium allergy. Contact Dermatitis 2021;85(5):514-522. PubMed

See these in context on the Chromium monograph →

Cassia Cinnamon 20 references
  1. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
  2. Khan A, Safdar M, Ali Khan M, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215-8. PubMed
  3. De Benito V, Alzaga R. Occupational allergic contact dermatitis from cassia (Chinese cinnamon) as a flavouring agent in coffee. Contact Dermatitis 1999;40:165. PubMed
  4. Drake TE, Maibach HI. Allergic contact dermatitis and stomatitis caused by a cinnamic aldehyde-flavored toothpaste. Arch Dermatol 1976;112:202-3.
  5. Press release. Cinnamon capsules to reduce blood sugar are medicinal products! Efficacy has not been scientifically proven - some products contain high levels of coumarin. Federal Institute of Risk Assessment (BfM), Germany, November 11, 2006. Available a
  6. Felter SP, Vassallo JD, Carlton BD, Daston GP. A safety assessment of coumarin taking into account species-specificity of toxicokinetics. Food Chem Toxicol 2006;44:462-75. PubMed
  7. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med 2009;22:507-12. PubMed
  8. Akilen, R., Tsiami, A., Devendra, D., and Robinson, N. Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial. Diabet.Med. 2010; PubMed
  9. Lu T, Sheng H Wu J Cheng Y Zhu J Chen Y. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutr Res. 2012;32(6):408-412. PubMed
  10. Choi, J., Lee, K. T., Ka, H., Jung, W. T., Jung, H. J., and Park, H. J. Constituents of the essential oil of the Cinnamomum cassia stem bark and the biological properties. Arch Pharm Res 2001;24(5):418-423.
  11. Altschuler JA, Casella SJ, MacKenzie TA, Curtis KM. The effect of cinnamon on A1C among adolescents with type 1 diabetes. Diabetes Care 2007;30(4):813-6. PubMed
  12. Stoecker BR, Zhan Z, Luo R, et al. Cinnamon extract lowers blood glucose in hyperglycemic subjects. FASEB J. 2010;22:722.1 (Abstract only). DOI
  13. Admani S, Hill H, Jacob SE. Cinnamon Sugar Scrub Dermatitis: "Natural" Is Not Always Best. Pediatr Dermatol. 2017;34(1):e42-e43. PubMed
  14. Isaac-Renton M, Li MK, Parsons LM. Cinnamon spice and everything not nice: many features of intraoral allergy to cinnamic aldehyde. Dermatitis. 2015;26(3):116-21. PubMed
  15. Vandersall A, Katta R. Eyelid dermatitis as a manifestation of systemic contact dermatitis to cinnamon. Dermatitis. 2015 Jul-Aug;26(4):189. PubMed
  16. Wickenberg J, Lindstedt S, Nilsson J, Hlebowicz J. Cassia cinnamon does not change the insulin sensitivity or the liver enzymes in subjects with impaired glucose tolerance. Nutr J 2014 Sep 24;13:96. PubMed
  17. Brancheau D, Patel B, Zughaib M. Do cinnamon supplements cause acute hepatitis? Am J Case Rep 2015;16:250-4. PubMed
  18. Shekarchizadeh-Esfahani P, Heydarpour F, Izadi F, Jalili C. The effect of cinnamon supplementation on liver enzymes in adults: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2021;58:102699. PubMed
  19. Bernaola J, Valverde-Monge M, Otal-Buesa M, Cullen D, Heras-Mendaza F. Cinnamon allergic contact cheilitis. Contact Dermatitis 2023;88(5):418-419. PubMed
  20. Patel K, Howard M, Tate B. Cheilitis caused by allergic contact dermatitis to cinnamon in chai tea: A case report. Contact Dermatitis 2023;88(3):239-240. PubMed

See these in context on the Cassia Cinnamon monograph →

Phenethylamine (pea) 9 references
  1. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  2. Sabelli H, Fink P, Fawcett J, et al. Sustained antidepressant effect of PEA replacement. J Neuropsychiatry Clin Neurosci. 1996;8(2):168-71.
  3. Xie Z, Miller G. Beta-phenylehtylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. J Pharmacol Exp Ther. 2008;325(2):617-28.
  4. Lukasik-Glebocka M, Sommerfeld K, Tezyk A, et al. [Acute poisoning with weight-loss dietary supplement falsely suggesting the use of amphetamine]. Przegl Lek. 2013;70(10):880-3.
  5. Nakamura M, Ishii A, Nakahara D. Characterization of beta-phenyltheylamine-induced monoamine release in rat nucleus accumbens: a microdialysis study. Eur J Pharmacol. 1998;349(2-3):163-9.
  6. Bailey B, Philips S, Boulton A. In vivo release of endogenous dopamine, 5-hydroxytryptamine and some of their metabolites from rat caudate nucleus by phenylethylamine. Neurochem Res. 1987;12(2):173-8. PubMed
  7. Mantegazza P, Riva M. Amphetamine-like activity of beta-phenethylamine after a monoamine oxidase inhibitor in vivo. Journal of Pharmacy and Pharmacology. 1963;151(1):472-8.
  8. Grimsby J, Toth M, Chen K, et al. Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet. 1997;17(2):206-10.
  9. Lindemann L, Hoener MC. A renaissance in trace amines inspired by a novel GPCR family. Trends Pharmacol Sci. 2005;26(5):274-81. PubMed

See these in context on the Phenethylamine (pea) monograph →

Caffeine 236 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  8. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  9. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  10. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  11. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  12. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  13. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  14. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  15. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed
  16. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  17. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. PubMed
  18. Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. PubMed
  19. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  20. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  21. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  22. Tobias JD. Caffeine in the treatment of apnea associated with respiratory syncytial virus infection in neonates and infants. South Med J 2000;93:297-304. DOI
  23. Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. PubMed
  24. Lloyd T, Johnson-Rollings N, Eggli DF, et al. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr 2000;19:256-61. PubMed
  25. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  26. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  27. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  28. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  29. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  30. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 1996:144:642-4. PubMed
  31. Avisar R, Avisar E, Weinberger D. Effect of coffee consumption on intraocular pressure. Ann Pharmacother 2002;36:992-5.. PubMed
  32. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. PubMed
  33. Horner NK, Lampe JW. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness. J Am Diet Assoc 2000;100:1368-80. PubMed
  34. Bracken MB, Triche EW, Belanger K, et al. Association of maternal caffeine consumption with decrements in fetal growth. Am J Epidemiol 2003;157:456-66.. PubMed
  35. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  36. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  37. Dreher HM. The effect of caffeine reduction on sleep quality and well-being in persons with HIV. J Psychosom Res 2003;54:191-8.. PubMed
  38. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  39. Schechter MD, Timmons GD. Objectively measured hyperactivity--II. Caffeine and amphetamine effects. J Clin Pharmacol 1985;25:276-80.. PubMed
  40. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI
  41. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  42. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  43. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  44. May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982;31:656-61. PubMed
  45. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. PubMed
  46. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  47. Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. DOI
  48. Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. PubMed
  49. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  50. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  51. Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. PubMed
  52. Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7.
  53. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
  54. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  55. Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. PubMed
  56. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004;176:1-29. PubMed
  57. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  58. Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. DOI
  59. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  60. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  61. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8. PubMed
  62. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  63. Shet, M. S., McPhaul, M., Fisher, C. W., Stallings, N. R., and Estabrook, R. W. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997;25(11):1298-1303.
  64. Staib, A. H., Stille, W., Dietlein, G., Shah, P. M., Harder, S., Mieke, S., and Beer, C. Interaction between quinolones and caffeine. Drugs 1987;34 Suppl 1:170-174. PubMed
  65. Stille, W., Harder, S., Mieke, S., Beer, C., Shah, P. M., Frech, K., and Staib, A. H. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J.Antimicrob.Chemother. 1987;20(5):729-734. PubMed
  66. Fuhr, U., Strobl, G., Manaut, F., Anders, E. M., Sorgel, F., Lopez-de-Brinas, E., Chu, D. T., Pernet, A. G., Mahr, G., Sanz, F., and . Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isof
  67. Kot, M. and Daniel, W. A. Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes. Pharmacol Rep. 2009;61(6):1216-1220. PubMed
  68. Gasior, M., Borowicz, K., Buszewicz, G., Kleinrok, Z., and Czuczwar, S. J. Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia 1996;37(3 PubMed
  69. Jankiewicz, K., Chroscinska-Krawczyk, M., Blaszczyk, B., and Czuczwar, S. J. [Caffeine and antiepileptic drugs: experimental and clinical data]. Przegl.Lek. 2007;64(11):965-967.
  70. Luszczki, J. J., Zuchora, M., Sawicka, K. M., Kozinska, J., and Czuczwar, S. J. Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures i
  71. Chroscinska-Krawczyk, M., Jargiello-Baszak, M., Walek, M., Tylus, B., and Czuczwar, S. J. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol.Rep. 2011;63(1):12-18. PubMed
  72. Vaz, J., Kulkarni, C., David, J., and Joseph, T. Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. Indian J.Exp.Biol. 1998;36(1):112-114.
  73. Gasior, M., Swiader, M., Przybylko, M., Borowicz, K., Turski, W. A., Kleinrok, Z., and Czuczwar, S. J. Felbamate demonstrates low propensity for interaction with methylxanthines and Ca2+ channel modulators against experimental seizures in mice. Eur.J Phar PubMed
  74. Balogh, A., Klinger, G., Henschel, L., Borner, A., Vollanth, R., and Kuhnz, W. Influence of ethinylestradiol-containing combination oral contraceptives with gestodene or levonorgestrel on caffeine elimination. Eur.J.Clin.Pharmacol. 1995;48(2):161-166. PubMed
  75. Mohiuddin, M., Azam, A. T., Amran, M. S., and Hossain, M. A. In vive effects of gliclazide and metformin on the plasma concentration of caffeine in healthy rats. Pak.J Biol Sci 5-1-2009;12(9):734-737.
  76. Mays, D. C., Camisa, C., Cheney, P., Pacula, C. M., Nawoot, S., and Gerber, N. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin.Pharmacol.Ther. 1987;42(6):621-626. PubMed
  77. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  78. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.
  79. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  80. Bailey, D. N., Weibert, R. T., Naylor, A. J., and Shaw, R. F. A study of salicylate and caffeine excretion in the breast milk of two nursing mothers. J.Anal.Toxicol. 1982;6(2):64-68. PubMed
  81. Griffiths, R. R. and Chausmer, A. L. Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Nihon Shinkei Seishin Yakurigaku Zasshi 2000;20(
  82. Karacan, I., Thornby, J. I., Anch, M., Booth, G. H., Williams, R. L., and Salis, P. J. Dose-related sleep disturbances induced by coffee and caffeine. Clin Pharmacol Ther 1976;20(6):682-689. PubMed
  83. Quirce, G. S., Freire, P., Fernandez, R. M., Davila, I., and Losada, E. Urticaria from caffeine. J.Allergy Clin Immunol. 1991;88(4):680-681. PubMed
  84. Hughes, J. R., Higgins, S. T., Bickel, W. K., Hunt, W. K., Fenwick, J. W., Gulliver, S. B., and Mireault, G. C. Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Arch.Gen.Psychiatry 1991;48(7):611-617. PubMed
  85. Adams, B. A. and Brubaker, R. F. Caffeine has no clinically significant effect on aqueous humor flow in the normal human eye. Ophthalmology 1990;97(8):1030-1031. PubMed
  86. Davis, R. H. Does caffeine ingestion affect intraocular pressure?. Ophthalmology 1989;96(11):1680-1681. PubMed
  87. Higginbotham, E. J., Kilimanjaro, H. A., Wilensky, J. T., Batenhorst, R. L., and Hermann, D. The effect of caffeine on intraocular pressure in glaucoma patients. Ophthalmology 1989;96(5):624-626.
  88. Wrenn, K. D. and Oschner, I. Rhabdomyolysis induced by a caffeine overdose. Ann.Emerg.Med. 1989;18(1):94-97. PubMed
  89. Pola, J., Subiza, J., Armentia, A., Zapata, C., Hinojosa, M., Losada, E., and Valdivieso, R. Urticaria caused by caffeine. Ann.Allergy 1988;60(3):207-208.
  90. Lane, J. D. and Williams, R. B., Jr. Cardiovascular effects of caffeine and stress in regular coffee drinkers. Psychophysiology 1987;24(2):157-164. PubMed
  91. Shirlow, M. J. and Mathers, C. D. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. Int.J.Epidemiol. 1985;14(2):239-248. PubMed
  92. Stillner, V., Popkin, M. K., and Pierce, C. M. Caffeine-induced delirium during prolonged competitive stress. Am.J.Psychiatry 1978;135(7):855-856. PubMed
  93. Levy, M. and Zylber-Katz, E. Caffeine metabolism and coffee-attributed sleep disturbances. Clin Pharmacol Ther 1983;33(6):770-775. PubMed
  94. Brown, S. L., Salive, M. E., Pahor, M., Foley, D. J., Corti, M. C., Langlois, J. A., Wallace, R. B., and Harris, T. B. Occult caffeine as a source of sleep problems in an older population. J.Am.Geriatr.Soc. 1995;43(8):860-864. PubMed
  95. Sung, B. H., Whitsett, T. L., Lovallo, W. R., al'Absi, M., Pincomb, G. A., and Wilson, M. F. Prolonged increase in blood pressure by a single oral dose of caffeine in mildly hypertensive men. Am.J Hypertens. 1994;7(8):755-758. PubMed
  96. Caballero, T., Garcia-Ara, C., Pascual, C., Diaz-Pena, J. M., and Ojeda, A. Urticaria induced by caffeine. J.Investig.Allergol.Clin Immunol. 1993;3(3):160-162.
  97. Smits, P., Temme, L., and Thien, T. The cardiovascular interaction between caffeine and nicotine in humans. Clin Pharmacol Ther 1993;54(2):194-204. PubMed
  98. Garrett, B. E. and Griffiths, R. R. Physical dependence increases the relative reinforcing effects of caffeine versus placebo. Psychopharmacology (Berl) 1998;139(3):195-202. PubMed
  99. Lane, J. D. and Phillips-Bute, B. G. Caffeine deprivation affects vigilance performance and mood. Physiol Behav. 1998;65(1):171-175. PubMed
  100. Boekema, P. J., Samsom, M., van Berge Henegouwen, G. P., and Smout, A. J. Coffee and gastrointestinal function: facts and fiction. A review. Scand J Gastroenterol.Suppl 1999;230:35-39. PubMed
  101. Terry, P., Lagergren, J., Wolk, A., and Nyren, O. Reflux-inducing dietary factors and risk of adenocarcinoma of the esophagus and gastric cardia. Nutr Cancer 2000;38(2):186-191.
  102. Pollak, C. P. and Bright, D. Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth-graders. Pediatrics 2003;111(1):42-46. PubMed
  103. DiBaise, J. K. A randomized, double-blind comparison of two different coffee-roasting processes on development of heartburn and dyspepsia in coffee-sensitive individuals. Dig.Dis.Sci 2003;48(4):652-656. PubMed
  104. Wang, J. H., Luo, J. Y., Dong, L., Gong, J., and Tong, M. Epidemiology of gastroesophageal reflux disease: a general population-based study in Xi'an of Northwest China. World J Gastroenterol. 6-1-2004;10(11):1647-1651. PubMed
  105. Naliboff, B. D., Mayer, M., Fass, R., Fitzgerald, L. Z., Chang, L., Bolus, R., and Mayer, E. A. The effect of life stress on symptoms of heartburn. Psychosom.Med 2004;66(3):426-434. PubMed
  106. Massey, L. K. and Sutton, R. A. Acute caffeine effects on urine composition and calcium kidney stone risk in calcium stone formers. J.Urol. 2004;172(2):555-558. PubMed
  107. Tavani, A. and La, Vecchia C. Coffee, decaffeinated coffee, tea and cancer of the colon and rectum: a review of epidemiological studies, 1990-2003. Cancer Causes Control 2004;15(8):743-757. PubMed
  108. Noordzij, M., Uiterwaal, C. S., Arends, L. R., Kok, F. J., Grobbee, D. E., and Geleijnse, J. M. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens. 2005;23(5):921-928. PubMed
  109. Chandrasekaran, S., Rochtchina, E., and Mitchell, P. Effects of caffeine on intraocular pressure: the Blue Mountains Eye Study. J Glaucoma. 2005;14(6):504-507. PubMed
  110. Morgan, J. C. and Sethi, K. D. Drug-induced tremors. Lancet Neurol. 2005;4(12):866-876. PubMed
  111. Doan, B. K., Hickey, P. A., Lieberman, H. R., and Fischer, J. R. Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Aviat.Space Environ Med 2006;77(10):1034-1040.
  112. Whalen, D. J., Silk, J. S., Semel, M., Forbes, E. E., Ryan, N. D., Axelson, D. A., Birmaher, B., and Dahl, R. E. Caffeine consumption, sleep, and affect in the natural environments of depressed youth and healthy controls. J Pediatr.Psychol. 2008;33(4):35 PubMed
  113. MacKenzie, T., Comi, R., Sluss, P., Keisari, R., Manwar, S., Kim, J., Larson, R., and Baron, J. A. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-1698. PubMed
  114. Mort, J. R. and Kruse, H. R. Timing of blood pressure measurement related to caffeine consumption. Ann Pharmacother. 2008;42(1):105-110.
  115. Ganmaa, D., Willett, W. C., Li, T. Y., Feskanich, D., van Dam, R. M., Lopez-Garcia, E., Hunter, D. J., and Holmes, M. D. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer 5-1-2008;122(9):2071-2076. PubMed
  116. Killgore, W. D., Rupp, T. L., Grugle, N. L., Reichardt, R. M., Lipizzi, E. L., and Balkin, T. J. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness. J Sleep Res 2008;17(3):3 PubMed
  117. Ozsungur, S., Brenner, D., and El-Sohemy, A. Fourteen well-described caffeine withdrawal symptoms factor into three clusters. Psychopharmacology (Berl) 2009;201(4):541-548. PubMed
  118. Ishitani, K., Lin, J., Manson, J. E., Buring, J. E., and Zhang, S. M. Caffeine consumption and the risk of breast cancer in a large prospective cohort of women. Arch Intern Med 10-13-2008;168(18):2022-2031. PubMed
  119. Tunnicliffe, J. M., Erdman, K. A., Reimer, R. A., Lun, V., and Shearer, J. Consumption of dietary caffeine and coffee in physically active populations: physiological interactions. Appl Physiol Nutr Metab 2008;33(6):1301-1310. PubMed
  120. Sin, C. W., Ho, J. S., and Chung, J. W. Systematic review on the effectiveness of caffeine abstinence on the quality of sleep. J Clin Nurs. 2009;18(1):13-21. PubMed
  121. Lopez-Garcia, E., Rodriguez-Artalejo, F., Rexrode, K. M., Logroscino, G., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of stroke in women. Circulation 3-3-2009;119(8):1116-1123. PubMed
  122. Zhang, W., Lopez-Garcia, E., Li, T. Y., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of cardiovascular diseases and all-cause mortality among men with type 2 diabetes. Diabetes Care 2009;32(6):1043-1045. PubMed
  123. Killgore, W. D., Kahn-Greene, E. T., Grugle, N. L., Killgore, D. B., and Balkin, T. J. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 2-1-2009;32(2):205-216. PubMed
  124. Natale, F., Cirillo, C., Di Marco, G. M., di Vetta, L. S., Aronne, L., Siciliano, A., Mocerino, R., Tedesco, M. A., Golino, P., and Calabro, R. When chewing gum is more than just a bad habit. Lancet 5-30-2009;373(9678):1918. PubMed
  125. Calamaro, C. J., Mason, T. B., and Ratcliffe, S. J. Adolescents living the 24/7 lifestyle: effects of caffeine and technology on sleep duration and daytime functioning. Pediatrics 2009;123(6):e1005-e1010. PubMed
  126. Koran, L. M., Aboujaoude, E., and Gamel, N. N. Double-blind study of dextroamphetamine versus caffeine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2009;70(11):1530-1535. PubMed
  127. Luebbe, A. M. and Bell, D. J. Mountain Dew or mountain don't?: a pilot investigation of caffeine use parameters and relations to depression and anxiety symptoms in 5th- and 10th-grade students. J Sch Health 2009;79(8):380-387.
  128. Skouroliakou, M., Bacopoulou, F., and Markantonis, S. L. Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial. J Paediatr.Child Health 2009;45(10):587-592. PubMed
  129. Urade, Y. [Molecular mechanisms of insomnia]. Nippon Rinsho 2009;67(8):1489-1493.
  130. Montandon, G., Horner, R. L., Kinkead, R., and Bairam, A. Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats. J Physiol 11-15-2009;587(Pt 22):5493-5507. PubMed
  131. Addicott, M. A. and Laurienti, P. J. A comparison of the effects of caffeine following abstinence and normal caffeine use. Psychopharmacology (Berl) 2009;207(3):423-431. PubMed
  132. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433. PubMed
  133. Moisey, L. L., Robinson, L. E., and Graham, T. E. Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males. Br.J Nutr. 2010;103(6):833-841. PubMed
  134. Chroscinska-Krawczyk, M., Ratnaraj, N., Patsalos, P. N., and Czuczwar, S. J. Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep. 2009;61(5):819 PubMed
  135. Attwood, A., Terry, P., and Higgs, S. Conditioned effects of caffeine on performance in humans. Physiol Behav 3-3-2010;99(3):286-293. PubMed
  136. Skinner, T. L., Jenkins, D. G., Coombes, J. S., Taaffe, D. R., and Leveritt, M. D. Dose response of caffeine on 2000-m rowing performance. Med Sci Sports Exerc. 2010;42(3):571-576. PubMed
  137. Holick, C. N., Smith, S. G., Giovannucci, E., and Michaud, D. S. Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies. Cancer Epidemiol.Biomarkers Prev 2010;19(1):39-47. PubMed
  138. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  139. Buscemi, S., Verga, S., Batsis, J. A., Donatelli, M., Tranchina, M. R., Belmonte, S., Mattina, A., Re, A., and Cerasola, G. Acute effects of coffee on endothelial function in healthy subjects. Eur.J Clin Nutr. 2010;64(5):483-489. PubMed
  140. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  141. Greenwood, D. C., Alwan, N., Boylan, S., Cade, J. E., Charvill, J., Chipps, K. C., Cooke, M. S., Dolby, V. A., Hay, A. W., Kassam, S., Kirk, S. F., Konje, J. C., Potdar, N., Shires, S., Simpson, N., Taub, N., Thomas, J. D., Walker, J., White, K. L., and
  142. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  143. Brick, C. A., Seely, D. L., and Palermo, T. M. Association between sleep hygiene and sleep quality in medical students. Behav Sleep Med 2010;8(2):113-121. PubMed
  144. Digdon, N. L. Circadian preference and college students' beliefs about sleep education. Chronobiol.Int 2010;27(2):297-317. PubMed
  145. Boos, C. J., White, S. H., Bland, S. A., and McAllister, P. D. Dietary supplements and military operations: caution is advised. J R.Army Med Corps 2010;156(1):41-43. PubMed
  146. Casiglia, E., Bongiovi, S., Paleari, C. D., Petucco, S., Boni, M., Colangeli, G., Penzo, M., and Pessina, A. C. Haemodynamic effects of coffee and caffeine in normal volunteers: a placebo-controlled clinical study. J.Intern.Med. 1991;229(6):501-504. PubMed
  147. Aguggia, M. and Saracco, M. G. Pathophysiology of migraine chronification. Neurol.Sci 2010;31 Suppl 1:S15-S17. PubMed
  148. Torelli, P. and Manzoni, G. C. Fasting headache. Curr Pain Headache Rep. 2010;14(4):284-291.
  149. Farag, N. H., Whitsett, T. L., McKey, B. S., Wilson, M. F., Vincent, A. S., Everson-Rose, S. A., and Lovallo, W. R. Caffeine and blood pressure response: sex, age, and hormonal status. J Womens Health (Larchmt.) 2010;19(6):1171-1176. PubMed
  150. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  151. Suen, L. K., Tam, W. W., and Hon, K. L. Association of sleep hygiene-related factors and sleep quality among university students in Hong Kong. Hong.Kong.Med.J 2010;16(3):180-185.
  152. Stafford, L. D., Wright, C., and Yeomans, M. R. The drink remains the same: implicit positive associations in high but not moderate or non-caffeine users. Psychol.Addict.Behav. 2010;24(2):274-281. PubMed
  153. Conen, D., Chiuve, S. E., Everett, B. M., Zhang, S. M., Buring, J. E., and Albert, C. M. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr 2010;92(3):509-514. PubMed
  154. Freire, R. C., Perna, G., and Nardi, A. E. Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment. Harv.Rev.Psychiatry 2010;18(4):220-229. PubMed
  155. Reis, J. P., Loria, C. M., Steffen, L. M., Zhou, X., van, Horn L., Siscovick, D. S., Jacobs, D. R., Jr., and Carr, J. J. Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study. A PubMed
  156. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  157. Kujawa-Hadrys, M., Tosik, D., and Bartel, H. Changes in thickness of each layer of developing chicken cornea after administration of caffeine. Folia Histochem.Cytobiol. 2010;48(2):273-277. PubMed
  158. Boggs, D. A., Palmer, J. R., Stampfer, M. J., Spiegelman, D., Adams-Campbell, L. L., and Rosenberg, L. Tea and coffee intake in relation to risk of breast cancer in the Black Women's Health Study. Cancer Causes Control 2010;21(11):1941-1948. PubMed
  159. Li, S., Zhu, S., Jin, X., Yan, C., Wu, S., Jiang, F., and Shen, X. Risk factors associated with short sleep duration among Chinese school-aged children. Sleep Med. 2010;11(9):907-916. PubMed
  160. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  161. Knight, J. M., Avery, E. F., Janssen, I., and Powell, L. H. Cortisol and depressive symptoms in a population-based cohort of midlife women. Psychosom.Med. 2010;72(9):855-861. PubMed
  162. Porkka-Heiskanen, T. Methylxanthines and sleep. Handb.Exp.Pharmacol 2011;(200):331-348. PubMed
  163. Mostofsky, E., Schlaug, G., Mukamal, K. J., Rosamond, W. D., and Mittleman, M. A. Coffee and acute ischemic stroke onset: the Stroke Onset Study. Neurology 11-2-2010;75(18):1583-1588. PubMed
  164. Orozco-Gregorio, H., Mota-Rojas, D., Bonilla-Jaime, H., Trujillo-Ortega, M. E., Becerril-Herrera, M., Hernandez-Gonzalez, R., and Villanueva-Garcia, D. Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia PubMed
  165. Li, G. Z., Zhang, N., Du, P., Yang, Y., Wu, S. L., Xiao, Y. X., Jin, R., Liu, L., Shen, H., and Dai, Y. Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms: a Chinese multi-center study. Chin Med
  166. Duvnjak-Zaknich, D. M., Dawson, B. T., Wallman, K. E., and Henry, G. Effect of caffeine on reactive agility time when fresh and fatigued. Med.Sci.Sports Exerc. 2011;43(8):1523-1530. PubMed
  167. Astorino, T. A., Martin, B. J., Schachtsiek, L., Wong, K., and Ng, K. Minimal effect of acute caffeine ingestion on intense resistance training performance. J Strength.Cond.Res 2011;25(6):1752-1758. PubMed
  168. Kivity, S., Ben Aharon, Y., Man, A., and Topilsky, M. The effect of caffeine on exercise-induced bronchoconstriction. Chest 1990;97(5):1083-1085. PubMed
  169. Lubin, F. and Ron, E. Consumption of methylxanthine-containing beverages and the risk of breast cancer. Cancer Lett. 1990;53(2-3):81-90. PubMed
  170. Smits, P., Lenders, J. W., and Thien, T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin.Pharmacol.Ther. 1990;48(4):410-418. PubMed
  171. Rossignol, A. M. and Bonnlander, H. Caffeine-containing beverages, total fluid consumption, and premenstrual syndrome. Am.J.Public Health 1990;80(9):1106-1110. PubMed
  172. Birkett, N. J. and Logan, A. G. Caffeine-containing beverages and the prevalence of hypertension. J Hypertens.Suppl 1988;6(4):S620-S622. PubMed
  173. Fraumeni, J. F., Jr., Scotto, J., and Dunham, L. J. Coffee-drinking and bladder cancer. Lancet 11-27-1971;2(7735):1204. PubMed
  174. Greden, J. F. Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry 1974;131(10):1089-1092. PubMed
  175. Whitsett, T. L., Manion, C. V., and Christensen, H. D. Cardiovascular effects of coffee and caffeine. Am.J.Cardiol. 3-15-1984;53(7):918-922. PubMed
  176. Firestone, P., Poitras-Wright, H., and Douglas, V. The effects of caffeine on hyperactive children. J.Learn.Disabil. 1978;11(3):133-141. PubMed
  177. Thomas, F. B., Steinbaugh, J. T., Fromkes, J. J., Mekhjian, H. S., and Caldwell, J. H. Inhibitory effect of coffee on lower esophageal sphincter pressure. Gastroenterology 1980;79(6):1262-1266. DOI
  178. Linn, S., Schoenbaum, S. C., Monson, R. R., Rosner, B., Stubblefield, P. G., and Ryan, K. J. No association between coffee consumption and adverse outcomes of pregnancy. N.Engl.J Med 1-21-1982;306(3):141-145. PubMed
  179. Cohen, S. Pathogenesis of coffee-induced gastrointestinal symptoms. N.Engl.J Med 7-17-1980;303(3):122-124. PubMed
  180. Feldman, M. and Barnett, C. Relationships between the acidity and osmolality of popular beverages and reported postprandial heartburn. Gastroenterology 1995;108(1):125-131. PubMed
  181. Quinlan, P., Lane, J., and Aspinall, L. Effects of hot tea, coffee and water ingestion on physiological responses and mood: the role of caffeine, water and beverage type. Psychopharmacology (Berl) 1997;134(2):164-173. PubMed
  182. Youngstedt, S. D., O'Connor, P. J., Crabbe, J. B., and Dishman, R. K. Acute exercise reduces caffeine-induced anxiogenesis. Med.Sci Sports Exerc. 1998;30(5):740-745. PubMed
  183. Kaminsky, L. A., Martin, C. A., and Whaley, M. H. Caffeine consumption habits do not influence the exercise blood pressure response following caffeine ingestion. J.Sports Med.Phys.Fitness 1998;38(1):53-58.
  184. McManamy, M. C. and Schube, P. G. Caffeine intoxication: report of a case the symptoms of which amounted to a psychosis. New England Journal of Medicine 1936;215:616-620. DOI
  185. Richter, J. E., Katz, P. O., and Waring, J. P. Gastroesophageal Reflux Disease. IFFGD 2000;
  186. Hsu, C., Harden, R. N., and Houle, T. Nicotine and caffeine intake in complex regional pain syndrome. Journal of Back and Musculoskeletal Rehabilitation 2002;16(1):33-38. PubMed
  187. Luebbe, A. M. Child and Adolescent Anxiety Sensitivity, Perceived Subjective Effects of Caffeine and Caffeine Consumption. J Caffeine Res 2011;1(4):213-218. DOI
  188. Li-Neng, Y., Greenstadt, L., and Shapiro, D. Effects of caffeine on blood pressure:A cross-cultural comparison. Psychophysiology 1983;20
  189. Fotherby, M. D., Ghandi, C., Haigh, R. A., Macdonald, T. A., and Potter, J. F. Sustained caffeine use has no pressor effect in the elderly. Cardiology in the Elderly 1994;2(6):499-503.
  190. Basurto Ona X, Uriona Tuma SM, Martínez García L, Solà I, Bonfill Cosp X. Drug therapy for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2013 28;2:CD001792. doi: 10.1002/14651858.CD001792.pub3. Review. PubMed
  191. Beaudoin MS, Allen B, Mazzetti G, Sullivan PJ, Graham TE. Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women. Appl Physiol Nutr Metab. 2013;38(2):140-7. doi: 10.1139/apnm-2012-0201. Epub 2012 9. PubMed
  192. Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J. Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart. 2013;99(19):1383-9. doi: 10.1136/heartjnl-2013-303950. Re PubMed
  193. Chen L, Bell EM, Browne ML, Druschel CM, Romitti PA, Schmidt RJ, Burns TL, Moslehi R, Olney RS; National Birth Defects Prevention Study. Maternal caffeine consumption and risk of congenital limb deficiencies. Birth Defects Res A Clin Mol Teratol. 2012 De PubMed
  194. Chen LW, Wu Y, Neelakantan N, Chong MF, Pan A, van Dam RM. Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis. BMC Med. 2014 19;12:174. doi: 10.1186/s12916-014-0174-6 PubMed
  195. Cheng M, Hu Z, Lu X, Huang J, Gu D. Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies. Can J Cardiol. 2014 Apr;30(4):448-54. doi: 10.1016/j.cjca.2013.12.026. Epub 2014 2. Review. PubMed
  196. Chiaffarino F, Bravi F, Cipriani S, Parazzini F, Ricci E, Viganò P, La Vecchia C. Coffee and caffeine intake and risk of endometriosis: a meta-analysis. Eur J Nutr. 2014 Oct;53(7):1573-9. doi: 10.1007/s00394-014-0662-7. Epub 2014 31. PubMed
  197. Greenwood DC, Thatcher NJ, Ye J, Garrard L, Keogh G, King LG, Cade JE. Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis. Eur J Epidemiol. 2014;29(10):725-34. doi: 10.1007/s10654-014-9944-x. PubMed
  198. Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies. Gynecol Oncol. 2013 Jun;129(3):620-9. doi: 10.1016/j.ygyno.2013.03.014. Epub 2013 25. Review. PubMed
  199. Lee SM, Choi NK, Lee BC, Cho KH, Yoon BW, Park BJ. Caffeine-containing medicines increase the risk of hemorrhagic stroke. Stroke. 2013 Aug;44(8):2139-43. doi: 10.1161/STROKEAHA.111.674077. Epub 2013 6. PubMed
  200. Sanikini H, Dik VK, Siersema PD, Bhoo-Pathy N, Uiterwaal CS, Peeters PH, González CA, Zamora-Ros R, Overvad K, Tjønneland A, Roswall N, Boutron-Ruault MC, Fagherazzi G, Racine A, Kühn T, Katzke V, Boeing H, Trichopoulou A, Trichopoulos D, Lagiou P, Palli
  201. Simonin C, Duru C, Salleron J, Hincker P, Charles P, Delval A, Youssov K, Burnouf S, Azulay JP, Verny C, Scherer C, Tranchant C, Goizet C, Debruxelles S, Defebvre L, Sablonnière B, Romon-Rousseaux M, Buée L, Destée A, Godefroy O, Dürr A, Landwehrmeyer B;
  202. Szpak A, Allen D. A case of acute suicidality following excessive caffeine intake. J Psychopharmacol. 2012 Nov;26(11):1502-10. doi: 10.1177/0269881112442788. Epub 2012 2. PubMed
  203. van der Hoeven N, Visser I, Schene A, van den Born BJ. Severe hypertension related to caffeinated coffee and tranylcypromine: a case report. Ann Intern Med. 2014 May 6;160(9):657-8. doi: 10.7326/L14-5009-8. No abstract available. PubMed
  204. Dixit S, Stein PK, Dewland TA, Dukes JW, Vittinghoff E, Heckbert SR, Marcus GM. Consumption of Caffeinated Products and Cardiac Ectopy. J Am Heart Assoc. 2016 26;5(1). pii: e002503. doi: 10.1161/JAHA.115.002503. PubMed
  205. Sheppard SG. A preliminary investigation of ibogaine: case reports and recommendations for further study. J Subst Abuse Treat. 1994 Jul-Aug;11(4):379-85. PubMed
  206. Zuchinali P, Riberio PA, Pimentel M, da Rosa PR, Zimerman LI, Rohde LE. Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies. Europace 2016 Feb;18(2):257-66. PubMed
  207. Rhee J, Kim R, Kim Y, et al. Maternal caffeine consumption during pregnancy and risk of low birth weight: a dose-response meta-analysis of observational studies. PLoS One. 2015 Jul 20;10(7):e0132334. PubMed
  208. Zuchinali P, Souza GC, Pimentel M, et al. Short-term effects of high-dose caffeine on cardiac arrhythmias in patients with heart failure: a randomized clinical trial. JAMA Intern Med. 2016 Dec 1;176(12):1752-59. PubMed
  209. Lystrup RM, Leggit JC. Caffeine toxicity due to supplement use in caffeine - naïve individual: a cautionary tale. Mil Med. 2015 Aug;180(8):e936-40. PubMed
  210. Magdalan J, Zawadzki M, Skowronek R, et al. Nonfatal and fata intoxications with pure caffeine - report of three different cases. Forensic Sci Med Pathol. 2017 Sep;13(3):355-58.
  211. Trexler ET, Smith-Ryan AE, Roelofs EJ, Hirsch KR, Persky AM, Mock AG. Effects of coffee and caffeine anhydrous intake during creatine loading. J Strength Cond Res. 2016 May;30(5):1438-46. PubMed
  212. Lagier D, Nee L, Guieu R, et al. Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: a randomized controlled clinical trial. Eur J Anaesthesiol. 2018 Apr 26. [Epub ahead of DOI
  213. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  214. Wang HR, Woo YS, Bahk WM. Caffeine-induced psychiatric manifestations: a review. Int Clin Psychopharmacol. 2015 Jul;30(4):179-82. PubMed
  215. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648. PubMed
  216. Vliegenthart R, Miedema M, Hutten GJ, van Kaam AH, Onland W. High versus standard dose caffeine for apnoea: a systematic review. Arch Dis Child Fetal Neonatal Ed 2018;103(6):F523-9. doi: 10.1136/archdischild-2017-313556. PubMed
  217. Modzelewska D, Bellocco R, Elfvin A, et al. Caffeine exposure during pregnancy, small for gestational age birth and neonatal outcome - results from the Norwegian Mother and Child Cohort Study. BMC Pregnancy Childbirth. 2019;19(1):80. PubMed
  218. Shen JG, Brooks MB, Cincotta J, Manjourides JD. Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: A systematic review and meta-analysis. J Sci Med Sport. 2019;22(2):232-238. PubMed
  219. Berglundh S, Vollrath M, Brantsæter AL, et al. Maternal caffeine intake during pregnancy and child neurodevelopment up to eight years of age-Results from the Norwegian Mother, Father and Child Cohort Study. Eur J Nutr. 2020. PubMed
  220. Jin F, Qiao C. Association of maternal caffeine intake during pregnancy with low birth weight, childhood overweight, and obesity: a meta-analysis of cohort studies. Int J Obes (Lond). 2020. PubMed
  221. Krittanawong C, Tunhasiriwet A, Wang Z, et al. Is caffeine or coffee consumption a risk for new-onset atrial fibrillation? A systematic review and meta-analysis. Eur J Prev Cardiol. 2020:2047487320908385. PubMed
  222. Zhang H, Lee ZX, Qiu A. Caffeine intake and cognitive functions in children. Psychopharmacology (Berl). 2020;237(10):3109-3116. PubMed
  223. Stojanovic E, Scanlan AT, Milanovic Z, Fox JL, Stankovic R, Dalbo VJ. Acute caffeine supplementation improves jumping, sprinting, and change-of-direction performance in basketball players when ingested in the morning but not evening. Eur J Sport Sci. 2021 PubMed
  224. Zheng KH, Zhu K, Wactawski-Wende J, et al. Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative. Int J Cancer 2021;149(12):2032-2044. PubMed
  225. Wang S, Li X, Yang Y, et al. Does coffee, tea and caffeine consumption reduce the risk of incident breast cancer? A systematic review and network meta-analysis. Public Health Nutr 2021;24(18):6377-6389. PubMed
  226. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Saudi Med J 2021;42(2):151-160. PubMed
  227. Hinkle SN, Gleason JL, Yisahak SF, et al. Assessment of Caffeine Consumption and Maternal Cardiometabolic Pregnancy Complications. JAMA Netw Open 2021;4(11):e2133401. PubMed
  228. Yartsev A, Peisah C. Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report. BMC Psychiatry 2021;21(1):192. PubMed
  229. Tinawi M. Severe Rhabdomyolysis Due to Strenuous Exercise With a Potential Role of a High-Caffeine Energy Drink. Cureus 2022;14(1):e20867. PubMed
  230. Gleason JL, Sundaram R, Mitro SD, et al. Association of maternal caffeine consumption during pregnancy with child growth. JAMA Netw Open. 2022;5(10):e2239609. PubMed
  231. Ismail RIH, Awad HA, Saber M, Shehata BM. Bone mineral content for preterm neonates treated with caffeine using dual energy X-ray absorptiometry: An observational study. J Neonatal Perinatal Med 2023;16(1):129-135. PubMed
  232. Zhao J, Huang Y, Yu X. Caffeine intake and the risk of incident kidney stones: a systematic review and meta-analysis. Int Urol Nephrol 2022;54(10):2457-2466. PubMed
  233. Abbas-Hashemi SA, Hosseininasab D, Rastgoo S, Shiraseb F, Asbaghi O. The effects of caffeine supplementation on blood pressure in adults: A systematic review and dose-response meta-analysis. Clin Nutr ESPEN 2023;58:165-177. PubMed
  234. Oliphant EA, Hanning SM, McKinlay CJD, Alsweiler JM. Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis. J Perinatol 2024;44(6):785-801. PubMed
  235. Kühne T, Wallace E, Herzig D, et al. Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over tr
  236. Song JJ, Eyabi JC, Awatramani PD, Mitchell BG, Nene SY. Sudden Reduction in Caffeine Intake Increases Serum Lithium Concentration to Supratherapeutic Level: A Case Report. Prim Care Companion CNS Disord 2024;26(2):23cr03642. PubMed

See these in context on the Caffeine monograph →

Magnesium 82 references
  1. Rodin SM, Johnson BF. Pharmacokinetic interactions with digoxin. Clin Pharmacokinet 1988;15:227-44.
  2. Covington TR, et al. Handbook of Nonprescription Drugs. 11th ed. Washington, DC: American Pharmaceutical Association, 1996.
  3. Dahle LO, Berg G, Hammar M, et al. The effect of oral magnesium substitution on pregnancy-induced leg cramps. Am J Obstet Gynecol 1995;173:175-80. PubMed
  4. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  5. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996;16:257-63. PubMed
  6. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1999. Available at: http://books.nap.edu/books/0309063507/html/index.html.
  7. Birrer RB, Shallash AJ, Totten V. Hypermagnesemia-induced fatality following epsom salt gargles. J Emerg Med 2002;22:185-8. PubMed
  8. Ryan MP. Diuretics and potassium/magnesium depletion. Directions for treatment. Am J Med 1987;82:38-47.. PubMed
  9. Hollifield JW. Magnesium depletion, diuretics, and arrhythmias. Am J Med 1987;82:30-7.. PubMed
  10. Heidenreich O. Mode of action of conventional and potassium-sparing diuretics--aspects with relevance to Mg-sparing effects. Magnesium 1984;3:248-56..
  11. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study. Cephalalgia 1996;16:436-40.. PubMed
  12. Wang F, Van Den Eeden SK, Ackerson LM, et al. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache 2003;43:601-10.. PubMed
  13. Sompolinsky D, Samra Z. Influence of magnesium and manganese on some biological and physical properties of tetracycline. J Bacteriol 1972;110:468-76.. PubMed
  14. Jeyabalan A, Caritis SN. Pharmacologic inhibition of preterm labor. Clin Obstet Gynecol 2002;45:99-113. PubMed
  15. Mittendorf R, Dambrosia J, Pryde PG, et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol 2002;186:1111-8.. PubMed
  16. Witlin AG, Sibai BM. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol 1998;92:883-9.. DOI
  17. Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev 2002;4:CD001060. . PubMed
  18. Davey MJ, Teubner D. A randomized controlled trial of magnesium sulfate, in addition to usual care, for rate control in atrial fibrillation. Ann Emerg Med 2005;45:347-53.. PubMed
  19. L'Hommedieu CS, Nicholas D, Armes DA, et al. Potentiation of magnesium sulfate--induced neuromuscular weakness by gentamicin, tobramycin, and amikacin. J Pediatr 1983;102:629-31..
  20. Dunn CJ, Goa KL. Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. Drugs 2001;61:685-712..
  21. Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr 2012;66:411-8. PubMed
  22. Koontz SL, Friedman SA, Schwartz ML. Symptomatic hypocalcemia after tocolytic therapy with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 2004;190(6):1773-6. PubMed
  23. Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 1989;161(1):35-6. PubMed
  24. Waisman GD, Mayorga LM, Cámera MI, et al. Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia? Am J Obstet Gynecol. 1988;159(2):308-9. PubMed
  25. Brown DD, Juhl RP. Decreased bioavailability of digoxin due to antacids and kaolin-pectin. N Engl J Med. 1976;295(19):1034-7. PubMed
  26. Allen MD, Greenblatt DJ, Harmatz JS, et al. Effect of magnesium--aluminum hydroxide and kaolin--pectin on absorption of digoxin from tablets and capsules. J Clin Pharmacol. 1981;21(1):26-30. PubMed
  27. Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an in vitro study. Thromb Haemost. 1996;76(1):88-93. DOI
  28. Ravn HB, Kristensen SD, Vissinger H, et al. Magnesium inhibits human platelets. Blood Coagul Fibrinolysis. 1996;7(2):241-4. PubMed
  29. Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an infusion study in healthy volunteers. Thromb Haemost. 1996;75(6):939-44. DOI
  30. Neuvonen PJ, Kivistö KT. The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations. Br J Clin Pharmacol. 1991;32(2):215-20. PubMed
  31. Kivistö KT, Neuvonen PJ. Enhancement of absorption and effect of glipizide by magnesium hydroxide. Clin Pharmacol Ther. 1991;49(1):39-43. PubMed
  32. Neuvonen PJ, Kivistö KT. Enhancement of drug absorption by antacids. An unrecognised drug interaction. Clin Pharmacokinet. 1994;27(2):120-8. PubMed
  33. Shechter, M., Merz, C. N., Paul-Labrador, M., Meisel, S. R., Rude, R. K., Molloy, M. D., Dwyer, J. H., Shah, P. K., and Kaul, S. Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart
  34. Ganzevoort, J. W., Hoogerwaard, E. M., and van der Post, J. A. [Hypocalcemic delirium due to magnesium sulphate therapy in a pregnant woman with pre-eclampsia]. Ned.Tijdschr.Geneeskd. 8-3-2002;146(31):1453-1456.
  35. Horner, S. M. Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction. Circulation 1992;86(3):774-779. PubMed
  36. Azria, E., Tsatsaris, V., Goffinet, F., Kayem, G., Mignon, A., and Cabrol, D. [Magnesium sulfate in obstetrics: current data]. J Gynecol.Obstet.Biol.Reprod.(Paris) 2004;33(6 Pt 1):510-517.
  37. Magee, L. A., Miremadi, S., Li, J., Cheng, C., Ensom, M. H., Carleton, B., Cote, A. M., and von Dadelszen, P. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with p
  38. Henyan, N. N., Gillespie, E. L., White, C. M., Kluger, J., and Coleman, C. I. Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis. Ann.Thorac.Surg. 2005;80(6):2402-2406. PubMed
  39. Li, J., Zhang, Q., Zhang, M., and Egger, M. Intravenous magnesium for acute myocardial infarction. Cochrane.Database.Syst.Rev. 2007;(2):CD002755. PubMed
  40. Doyle, L. W., Crowther, C. A., Middleton, P., Marret, S., and Rouse, D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane.Database.Syst.Rev. 2009;(1):CD004661. PubMed
  41. Han, S., Crowther, C. A., and Moore, V. Magnesium maintenance therapy for preventing preterm birth after threatened preterm labour. Cochrane.Database.Syst.Rev. 2010;(7):CD000940. PubMed
  42. Duley, L., Gulmezoglu, A. M., Henderson-Smart, D. J., and Chou, D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane.Database.Syst.Rev. 2010;(11):CD000025. PubMed
  43. Conde-Agudelo, A., Romero, R., and Kusanovic, J. P. Nifedipine in the management of preterm labor: a systematic review and metaanalysis. Am J Obstet.Gynecol. 2011;204(2):134-20. PubMed
  44. Wong, G. K., Boet, R., Poon, W. S., Chan, M. T., Gin, T., Ng, S. C., and Zee, B. C. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis. Crit Care 2011;15(1):R52. PubMed
  45. Magee, L., Sawchuck, D., Synnes, A., and von, Dadelszen P. SOGC Clinical Practice Guideline. Magnesium sulphate for fetal neuroprotection. J Obstet.Gynaecol.Can. 2011;33(5):516-529.
  46. Doyle, L. W. Antenatal magnesium sulfate and neuroprotection. Curr Opin Pediatr 2012;24(2):154-159. PubMed
  47. McDonald, S. D., Lutsiv, O., Dzaja, N., and Duley, L. A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use. Int J Gynaecol.Obstet. 2012;118(2):90-96. PubMed
  48. Gordon, M., Naidoo, K., Akobeng, A. K., and Thomas, A. G. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane.Database.Syst.Rev. 2012;7:CD009118. PubMed
  49. Dodd, J. M., Crowther, C. A., and Middleton, P. Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane.Database.Syst.Rev. 2012;12:CD003927. PubMed
  50. Wu, X., Wang, C., Zhu, J., Zhang, C., Zhang, Y., and Gao, Y. Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting. BMC.Cardiovasc.D PubMed
  51. Thorp, J. M., Jr., Katz, V. L., Campbell, D., and Cefalo, R. C. Hypersensitivity to magnesium sulfate. Am.J.Obstet.Gynecol. 1989;161(4):889-890. PubMed
  52. Duley L and Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. Cochrane Database of Systematic Reviews 2000;(3) PubMed
  53. Gibbins KJ, Browning KR, Lopes VV, Anderson BL, Rouse DJ. Evaluation of the clinical use of magnesium sulfate for cerebral palsy prevention. Obstet Gynecol 2013;121(2 Pt 1):235-40. PubMed
  54. Ji D. Oral magnesium sulfate causes perforation during bowel preparation for fiberoptic colonoscopy in patients with colorectal cancer. J Emerg Med 2012;43(4):716-7. PubMed
  55. Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet 2012;27(2):248-54. PubMed
  56. Yamasaki M, Funakoshi S, Matsuda S, Imazu T, Takeda Y, Murakami T, Maeda Y. Interaction of magnesium oxide with gastric acid secretion inhibitors in clinical pharmacotherapy. Eur J Clin Pharmacol 2014;70(8):921-4. PubMed
  57. Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, Do SH. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth. 2017 Feb;36:102-106. PubMed
  58. Ikee R, Toyoyama T, Endo T, Tsunoda M, Hashimoto N. Impact of sevelamer hydrochloride on serum magnesium concentrations in hemodialysis patients. Magnes Res. 2016 Apr 1;29(4):184-90. PubMed
  59. Miller ES, Sakowicz A, Leger E. Lange E, Yee LM. The association between receipt of intrapartum magnesium and postpartum hemorrhage. Am J Obstet Gynecol 2018;218(1 Suppl):S165.
  60. Rodríguez-Rubio L, Solis Garcia Del Pozo J, Nava E, Jordán J. Interaction between magnesium sulfate and neuromuscular blockers during the perioperative period. A systematic review and meta-analysis. J Clin Anesth. 2016;34:524-34. PubMed
  61. Brown RS. Magnesium Sulfate: Another Cause of a Solute Diuresis. Am J Kidney Dis. 2017;69(4):550-551. PubMed
  62. Park H, Qin R, Smith TJ, et al. North Central Cancer Treatment Group N10C2 (Alliance): a double-blind placebo-controlled study of magnesium supplements to reduce menopausal hot flashes. Menopause. 2015;22(6):627-32. PubMed
  63. Sakanoue M, Sanada J, Kanekura T. Skin eruption elicited by magnesium oxide (Maglax). J Dermatol. 2016;43(2):221-2.
  64. Iwamuro M, Saito S, Yoshioka M, et al. A Magnesium Oxide Bezoar. Intern Med. 2018;57(21):3087-3091. PubMed
  65. Vilchez G, Dai J, Kumar K, Mundy D, Kontopoulos E, Sokol RJ. Racial/ethnic disparities in magnesium sulfate neuroprotection: a subgroup analysis of a multicenter randomized controlled trial. J Matern Fetal Neonatal Med. 2018;31(17):2304-2311. PubMed
  66. Drug Safety Communication: FDA Recommends Against Prolonged Use of Magnesium Sulfate to Stop Pre-term Labor Due to Bone Changes in Exposed Babies. U.S. Food and Drug Administration (FDA), May 30, 2013. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM353
  67. Committee Opinion: Magnesium Sulfate Use in Obstetrics. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for Maternal-Fetal Medicine, Number 652, January 2016. https://www.acog.org/Clinical-Guidance-and-Publi
  68. Kashihara Y, Terao Y, Yoda K, et al. Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. Eur J Clin Pharmacol. 2019;75(3):351-361. PubMed
  69. Shepherd E, Salam RA, Manhas D, et al. Antenatal magnesium sulphate and adverse neonatal outcomes: A systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002988. PubMed
  70. Hong JY, Hong JY, Choi YS, et al. Antenatal magnesium sulfate treatment and risk of necrotizing enterocolitis in preterm infants born at less than 32 weeks of gestation. Sci Rep. 2020;10(1):12826. PubMed
  71. Schuh S, Sweeney J, Rumantir M, et al. Effect of nebulized magnesium vs placebo added to albuterol on hospitalization among children with refractory acute asthma treated in the emergency department: a randomized clinical trial. JAMA. 2020;324(20):2038-20 PubMed
  72. Almeida CED, Carvalho LR, Andrade CVC, Nascimento PD Jr, Barros GAM, Modolo NSP. Effects of magnesium sulphate on the onset time of rocuronium at different doses: a randomized clinical trial. Braz J Anesthesiol. 2021;71(5):482-8. PubMed
  73. Gochi Valdovinos A, Arriaga-Redondo M, Dejuan Bitriá E, Pérez Rodríguez I, Márquez Isidro E, Blanco Bravo D. Prenatal therapy with magnesium sulphate and intestinal obstruction due to meconium in preterm newborns. An Pediatr (Engl Ed). 2022 Feb;96(2):138- PubMed
  74. Iio K, Kondo E, Shibata E, et al. Long-term tocolysis with magnesium sulfate as a risk factor for low bone mass: a case series. J Med Cases. 2022 Feb;13(2):47-50. PubMed
  75. Eiraku K, Uozumi Y, Hieda M, Maruyama T, Nomura H. A senile case of heart failure associated with hypermagnesemia induced by magnesium-containing laxative agent. Geriatr Gerontol Int. 2022;22(10):897-899.
  76. Enayati A, Gin JH, Sajeev JK, et al. Efficacy of intravenous magnesium for the management of non-post operative atrial fibrillation with rapid ventricular response: A systematic review and meta-analysis. J Cardiovasc Electrophysiol 2023;34(5):1286-1295. PubMed
  77. Su YH, Luo DC, Pang Y. Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study. BMC Anesthesiol 2023;23(1):326. PubMed
  78. Han J, Park HY, Shin HJ, Chung SH, Do SH. Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial. Magnes Res 2023;36(2):31-39. PubMed
  79. Lee AT, Cordova JC, Jamplis RP, Pomicter GR. Posterior Reversible Encephalopathy Syndrome and Eclampsia in the Setting of Magnesium Toxicity: A Case Report. A A Pract 2023;17(11):e01726. PubMed
  80. Darmawan D, Rengganis I, Rumende CM, et al. Effectiveness and Safety of Nebulized Magnesium as Last Line Treatment in Adults with Acute Asthma Attack: A Systematic Review and Meta-Analysis. Acta Med Indones 2024;56(1):3-12.
  81. Shepherd ES, Goldsmith S, Doyle LW, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2024;5(5):CD004661. PubMed
  82. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Magnesium monograph →

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

See these in context on the Cocoa monograph →

Green Tea 219 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Mitscher LA, Mitscher LA, Jung M, Shankel D, et al. Chemoprotection: a review of the potential therapeutic antioxidant properties of green tea (Camellia sinensis) and certain of its constituents. Med Res Rev 1997;17:327-65.
  8. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  9. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  10. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  11. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  12. Booth SL, Madabushi HT, Davidson KW, et al. Tea and coffee brews are not dietary sources of vitamin K-1 (phylloquinone). J Am Diet Assoc 1995;95:82-3. PubMed
  13. Lou FQ, Zhang MF, Zhang XG, et al. A study on tea-pigment in prevention of atherosclerosis. Chin Med J (Engl) 1989;102:579-83.
  14. Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med 1992;21:334-50. PubMed
  15. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  16. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  17. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  18. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  19. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed
  20. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  21. Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. PubMed
  22. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  23. Weisburger JH. Tea and health: the underlying mechanisms. Proc Soc Exp Biol Med 1999;220:271-5. PubMed
  24. Taylor JR, Wilt VM. Probable antagonism of warfarin by green tea. Ann Pharmacother 1999;33:426-8. PubMed
  25. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  26. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  27. Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. PubMed
  28. Lloyd T, Johnson-Rollings N, Eggli DF, et al. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr 2000;19:256-61. PubMed
  29. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  30. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7. DOI
  31. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  32. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  33. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  34. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  35. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 1996:144:642-4. PubMed
  36. Pisters KM, Newman RA, Coldman B, et al. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol 2001;19:1830-8. PubMed
  37. Haller CA, Jacob P 3rd, Benowitz NL. Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clin Pharmacol Ther 2002;71:421-32. PubMed
  38. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. PubMed
  39. Horner NK, Lampe JW. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness. J Am Diet Assoc 2000;100:1368-80. PubMed
  40. Bracken MB, Triche EW, Belanger K, et al. Association of maternal caffeine consumption with decrements in fetal growth. Am J Epidemiol 2003;157:456-66.. PubMed
  41. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  42. Nehlig A, Debry G. Consequences on the newborn of chronic maternal consumption of coffee during gestation and lactation: a review. J Am Coll Nutr 1994;13:6-21.. PubMed
  43. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  44. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  45. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI
  46. Ahn WS, Yoo J, Huh SW, et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev 2003;12:383-90. PubMed
  47. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  48. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  49. Shirai T, Hayakawa H, Akiyama J, et al. Food allergy to green tea. J Allergy Clin Immunol 2003;112:805-6. PubMed
  50. Jatoi A, Ellison N, Burch PA, et al. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer 2003;97:1442-6.. PubMed
  51. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  52. May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982;31:656-61. PubMed
  53. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  54. Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. DOI
  55. Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. PubMed
  56. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  57. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  58. Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. PubMed
  59. Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7.
  60. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
  61. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  62. Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. PubMed
  63. Yang YC, Lu FH, Wu JS, et al. The protective effect of habitual tea consumption on hypertension. Arch Intern Med 2004 26;164:1534-40. PubMed
  64. Son DJ, Cho MR, Jin YR, et al. Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway. Prostaglandins Leukot Essent Fatty Acids 2004;71:25-31. PubMed
  65. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004;176:1-29. PubMed
  66. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  67. Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. DOI
  68. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  69. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  70. Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med 2006;144:68-71.
  71. Gloro R, Hourmand-Ollivier I, Mosquet B, et al. Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea. Eur J Gastroenterol Hepatol 2005;17:1135-7. PubMed
  72. Donovan JL, Chavin KD, Devane CL, et al. Green tea (Camellia sinensis) extract does not alter cytochrome P450 3A4 or 2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:906-8. PubMed
  73. Chu KO, Wang CC, Chu CY, et al. Pharmacokinetic studies of green tea catechins in maternal plasma and fetuses in rats. J Pharm Sci 2006;95:1372-81. PubMed
  74. Isbrucker RA, Edwards JA, Wolz E, et al. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. Food Chem Toxicol 2006;44:651-61. PubMed
  75. Navarro-Peran E, Cabezas-Herrera J, Garcia-Canovas F, et al. The antifolate activity of tea catechins. Cancer Res 2005;65:2059-64. PubMed
  76. Jimenez-Saenz M, Martinez-Sanchez, MDC. Acute hepatitis associated with the use of green tea infusions. J Hepatol 2006;44:616-9. PubMed
  77. Bradley Pharmaceuticals. Veregen Prescribing Information. October 2006.
  78. Correa A, Stolley A, Liu Y. Prenatal tea consumption and risks of anencephaly and spina bifida. Ann Epidemiol 2000;10:476-7. PubMed
  79. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8. PubMed
  80. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  81. Golden ED, Lam PY, Kardosh A, et al. Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood 2009;113:5927-37. PubMed
  82. Misaka S, Yatabe J, Muller F, et al. Green Tea Ingestion Greatly Reduces Plasma Concentrations of Nadolol in Healthy Subjects. Clin Pharmacol Ther 2014. [Epub ahead of print]. PubMed
  83. Roth M, Timmermann BN, Hagenbuch B. Interactions of green tea catechins with organic anion-transporting polypeptides. Drug Metab Dispos 2011;39:920-6. PubMed
  84. Kato Y, Miyazaki T, Kano T, et al. Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci 2009;98:2529-39. PubMed
  85. Chan, H. T., So, L. T., Li, S. W., Siu, C. W., Lau, C. P., and Tse, H. F. Effect of herbal consumption on time in therapeutic range of warfarin therapy in patients with atrial fibrillation. J.Cardiovasc.Pharmacol. 2011;58(1):87-90. PubMed
  86. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extrac
  87. Shet, M. S., McPhaul, M., Fisher, C. W., Stallings, N. R., and Estabrook, R. W. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997;25(11):1298-1303.
  88. Staib, A. H., Stille, W., Dietlein, G., Shah, P. M., Harder, S., Mieke, S., and Beer, C. Interaction between quinolones and caffeine. Drugs 1987;34 Suppl 1:170-174. PubMed
  89. Stille, W., Harder, S., Mieke, S., Beer, C., Shah, P. M., Frech, K., and Staib, A. H. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J.Antimicrob.Chemother. 1987;20(5):729-734. PubMed
  90. Fuhr, U., Strobl, G., Manaut, F., Anders, E. M., Sorgel, F., Lopez-de-Brinas, E., Chu, D. T., Pernet, A. G., Mahr, G., Sanz, F., and . Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isof
  91. Kot, M. and Daniel, W. A. Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes. Pharmacol Rep. 2009;61(6):1216-1220. PubMed
  92. Gasior, M., Borowicz, K., Buszewicz, G., Kleinrok, Z., and Czuczwar, S. J. Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia 1996;37(3 PubMed
  93. Jankiewicz, K., Chroscinska-Krawczyk, M., Blaszczyk, B., and Czuczwar, S. J. [Caffeine and antiepileptic drugs: experimental and clinical data]. Przegl.Lek. 2007;64(11):965-967.
  94. Luszczki, J. J., Zuchora, M., Sawicka, K. M., Kozinska, J., and Czuczwar, S. J. Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures i
  95. Chroscinska-Krawczyk, M., Jargiello-Baszak, M., Walek, M., Tylus, B., and Czuczwar, S. J. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol.Rep. 2011;63(1):12-18. PubMed
  96. Vaz, J., Kulkarni, C., David, J., and Joseph, T. Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. Indian J.Exp.Biol. 1998;36(1):112-114.
  97. Gasior, M., Swiader, M., Przybylko, M., Borowicz, K., Turski, W. A., Kleinrok, Z., and Czuczwar, S. J. Felbamate demonstrates low propensity for interaction with methylxanthines and Ca2+ channel modulators against experimental seizures in mice. Eur.J Phar PubMed
  98. Mohiuddin, M., Azam, A. T., Amran, M. S., and Hossain, M. A. In vive effects of gliclazide and metformin on the plasma concentration of caffeine in healthy rats. Pak.J Biol Sci 5-1-2009;12(9):734-737.
  99. Mays, D. C., Camisa, C., Cheney, P., Pacula, C. M., Nawoot, S., and Gerber, N. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin.Pharmacol.Ther. 1987;42(6):621-626. PubMed
  100. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  101. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.
  102. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  103. Wang, X. and Yeung, J. H. Effects of the aqueous extract from Salvia miltiorrhiza Bunge on caffeine pharmacokinetics and liver microsomal CYP1A2 activity in humans and rats. J Pharm Pharmacol 2010;62(8):1077-1083.
  104. Kot M, Daniel WA. Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep 2008;60:789-97.
  105. Kjaerstad MB, Nielsen F, Nohr-Jensen L, et al. Systemic uptake of miconazole during vaginal suppository use and effect on CYP1A2 and CYP3A4 associated enzyme activities in women. Eur J Clin Pharmacol 2010;66:1189-97. PubMed
  106. Goh BC, Reddy NJ, Dandamudi UB, et al. An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid t
  107. Chen Y, Kang Z, Yan J, et al. Liu wei di huang wan, a well-known traditional Chinese medicine induces CYP1A2 while suppressing CYP2A6 and N-acetyltransferase 2 acivities in man. J Ethnopharmacol 2010;132:213-8.
  108. Suzuki S, Murayama Y, Sugiyama E, et al. Estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, based on physiological liver development and serum protein levels. Yakugaku Zasshi 2010;130:613-20. PubMed
  109. Chien CF, Wu YT, Lee WC, et al. Herb-drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats. Chem Biol Interact 2010;184:458-65. PubMed
  110. Mills BM, Zaya MJ, Walters RR, et al. Current cytochrome P450 phenotyping methods applied to metabolic drug -drug interaction prediction in dogs. Drug Metab Dispos 2010;38:396-404. PubMed
  111. Turpault S, Brian W, Van Horn R, et al. Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6, and 3A. Br J Clin Pharmacol 2009;68:928-35. PubMed
  112. Filimonova AA, Ziganshina LE, Ziganshin AU, Chichirov AA. On the possibility of patient phenotyping on the basis of cytochrome p-450 1A2 isoenzyme activity using caffeine as the test substrate. Eksp Klin Farmakol 2009;72:61-5.
  113. Jenkins J, Williams D, Deng Y, et al. Eltrombopag, an oral thrombopoietin receptor agonist, has no impact on the pharmacokinetic profile of probe drugs for cytochrome P450 isoenzymes CYP3A4, CYP1A2, CYP2C9 and CYP2C19 in healthy men: a cocktail analysis.
  114. Chow, H. H., Cai, Y., Hakim, I. A., Crowell, J. A., Shahi, F., Brooks, C. A., Dorr, R. T., Hara, Y., and Alberts, D. S. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E i
  115. Gross, G., Meyer, K. G., Pres, H., Thielert, C., Tawfik, H., and Mescheder, A. A randomized, double-blind, four-arm parallel-group, placebo-controlled Phase II/III study to investigate the clinical efficacy of two galenic formulations of Polyphenon E in
  116. Stockfleth, E., Beti, H., Orasan, R., Grigorian, F., Mescheder, A., Tawfik, H., and Thielert, C. Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial. Br.J Dermatol. 2008;158(6):1329-1338.
  117. Smits, P., Temme, L., and Thien, T. The cardiovascular interaction between caffeine and nicotine in humans. Clin Pharmacol Ther 1993;54(2):194-204. PubMed
  118. MacKenzie, T., Comi, R., Sluss, P., Keisari, R., Manwar, S., Kim, J., Larson, R., and Baron, J. A. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-1698. PubMed
  119. Lopez-Garcia, E., Rodriguez-Artalejo, F., Rexrode, K. M., Logroscino, G., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of stroke in women. Circulation 3-3-2009;119(8):1116-1123. PubMed
  120. Zhang, W., Lopez-Garcia, E., Li, T. Y., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of cardiovascular diseases and all-cause mortality among men with type 2 diabetes. Diabetes Care 2009;32(6):1043-1045. PubMed
  121. Moisey, L. L., Robinson, L. E., and Graham, T. E. Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males. Br.J Nutr. 2010;103(6):833-841. PubMed
  122. Chroscinska-Krawczyk, M., Ratnaraj, N., Patsalos, P. N., and Czuczwar, S. J. Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep. 2009;61(5):819 PubMed
  123. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  124. Buscemi, S., Verga, S., Batsis, J. A., Donatelli, M., Tranchina, M. R., Belmonte, S., Mattina, A., Re, A., and Cerasola, G. Acute effects of coffee on endothelial function in healthy subjects. Eur.J Clin Nutr. 2010;64(5):483-489. PubMed
  125. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  126. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  127. Conen, D., Chiuve, S. E., Everett, B. M., Zhang, S. M., Buring, J. E., and Albert, C. M. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr 2010;92(3):509-514. PubMed
  128. Reis, J. P., Loria, C. M., Steffen, L. M., Zhou, X., van, Horn L., Siscovick, D. S., Jacobs, D. R., Jr., and Carr, J. J. Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study. A PubMed
  129. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  130. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  131. Perera, V., Gross, A. S., and McLachlan, A. J. Caffeine and paraxanthine HPLC assay for CYP1A2 phenotype assessment using saliva and plasma. Biomed.Chromatogr. 2010;24(10):1136-1144. PubMed
  132. Orozco-Gregorio, H., Mota-Rojas, D., Bonilla-Jaime, H., Trujillo-Ortega, M. E., Becerril-Herrera, M., Hernandez-Gonzalez, R., and Villanueva-Garcia, D. Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia PubMed
  133. Izzo, A. A. and Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009;69(13):1777-1798. PubMed
  134. Laurie, S. A., Miller, V. A., Grant, S. C., Kris, M. G., and Ng, K. K. Phase I study of green tea extract in patients with advanced lung cancer. Cancer Chemother.Pharmacol. 2005;55(1):33-38. PubMed
  135. Chiu, A. E., Chan, J. L., Kern, D. G., Kohler, S., Rehmus, W. E., and Kimball, A. B. Double-blinded, placebo-controlled trial of green tea extracts in the clinical and histologic appearance of photoaging skin. Dermatol Surg. 2005;31(7 Pt 2):855-860. PubMed
  136. Javaid, A. and Bonkovsky, H. L. Hepatotoxicity due to extracts of Chinese green tea (Camellia sinensis): a growing concern. J Hepatol 2006;45(2):334-335. PubMed
  137. Martinez-Sierra, C., Rendon, Unceta P., and Martin, Herrera L. [Acute hepatitis after green tea ingestion]. Med Clin (Barc.) 6-17-2006;127(3):119.
  138. Molinari, M., Watt, K. D., Kruszyna, T., Nelson, R., Walsh, M., Huang, W. Y., Nashan, B., and Peltekian, K. Acute liver failure induced by green tea extracts: case report and review of the literature. Liver Transpl. 2006;12(12):1892-1895. PubMed
  139. Chow, H. H., Hakim, I. A., Vining, D. R., Crowell, J. A., Cordova, C. A., Chew, W. M., Xu, M. J., Hsu, C. H., Ranger-Moore, J., and Alberts, D. S. Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer Epidemiol.B PubMed
  140. Federico, A., Tiso, A., and Loguercio, C. A case of hepatotoxicity caused by green tea. Free Radic.Biol Med 8-1-2007;43(3):474. PubMed
  141. Sarma, D. N., Barrett, M. L., Chavez, M. L., Gardiner, P., Ko, R., Mahady, G. B., Marles, R. J., Pellicore, L. S., Giancaspro, G. I., and Low, Dog T. Safety of green tea extracts : a systematic review by the US Pharmacopeia. Drug Saf 2008;31(6):469-484. PubMed
  142. Engdal, S. and Nilsen, O. G. In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients. Phytother.Res. 2009;23(7):906-912.
  143. Bergman, J. and Schjott, J. Hepatitis caused by Lotus-f3? Basic Clin Pharmacol.Toxicol. 2009;104(5):414-416. PubMed
  144. Kalus, U., Kiesewetter, H., and Radtke, H. Effect of CYSTUS052 and green tea on subjective symptoms in patients with infection of the upper respiratory tract. Phytother.Res. 2010;24(1):96-100.
  145. Tatti, S., Stockfleth, E., Beutner, K. R., Tawfik, H., Elsasser, U., Weyrauch, P., and Mescheder, A. Polyphenon E: a new treatment for external anogenital warts. Br.J Dermatol. 2010;162(1):176-184.
  146. Tsao, A. S., Liu, D., Martin, J., Tang, X. M., Lee, J. J., El-Naggar, A. K., Wistuba, I., Culotta, K. S., Mao, L., Gillenwater, A., Sagesaka, Y. M., Hong, W. K., and Papadimitrakopoulou, V. Phase II randomized, placebo-controlled trial of green tea extra
  147. Liatsos, G. D., Moulakakis, A., Ketikoglou, I., and Klonari, S. Possible green tea-induced thrombotic thrombocytopenic purpura. Am.J Health Syst.Pharm. 4-1-2010;67(7):531-534. PubMed
  148. Josic, J., Olsson, A. T., Wickeberg, J., Lindstedt, S., and Hlebowicz, J. Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: a randomized controlled trial. Nutr.J. 2010;9:63. PubMed
  149. Miller, R. J., Jackson, K. G., Dadd, T., Mayes, A. E., Brown, A. L., and Minihane, A. M. The impact of the catechol-O-methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract. Br.J.Nutr. 2011;105(8):1138-1144.
  150. Rohde, J., Jacobsen, C., and Kromann-Andersen, H. [Toxic hepatitis triggered by green tea]. Ugeskr.Laeger 1-17-2011;173(3):205-206.
  151. Tzellos, T. G., Sardeli, C., Lallas, A., Papazisis, G., Chourdakis, M., and Kouvelas, D. Efficacy, safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta-analysis. J.Eur.Acad.Dermatol.Ve PubMed
  152. Otera, H., Tada, K., Sakurai, T., Hashimoto, K., and Ikeda, A. Hypersensitivity pneumonitis associated with inhalation of catechin-rich green tea extracts. Respiration 2011;82(4):388-392. PubMed
  153. Yellapu, R. K., Mittal, V., Grewal, P., Fiel, M., and Schiano, T. Acute liver failure caused by 'fat burners' and dietary supplements: a case report and literature review. Can.J.Gastroenterol. 2011;25(3):157-160. PubMed
  154. Karth, A., Holoshitz, N., Kavinsky, C. J., Trohman, R., and McBride, B. F. A case report of atrial fibrillation potentially induced by hydroxycut: a multicomponent dietary weight loss supplement devoid of sympathomimetic amines. J.Pharm.Pract. 2010;23(3) PubMed
  155. Hsu, C. H., Liao, Y. L., Lin, S. C., Tsai, T. H., Huang, C. J., and Chou, P. Does supplementation with green tea extract improve insulin resistance in obese type 2 diabetics? A randomized, double-blind, and placebo-controlled clinical trial. Altern.Med.R
  156. Zheng XX, Xu YL, Li SH, et al. Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials. Am.J.Clin.Nutr. 2011;94:601-610. PubMed
  157. Miller, R. J., Jackson, K. G., Dadd, T., Mayes, A. E., Brown, A. L., Lovegrove, J. A., and Minihane, A. M. The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion. Mol.Nutr.Food Res.
  158. Bogdanski, P., Suliburska, J., Szulinska, M., Stepien, M., Pupek-Musialik, D., and Jablecka, A. Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, h
  159. Jurgens, T. M., Whelan, A. M., Killian, L., Doucette, S., Kirk, S., and Foy, E. Green tea for weight loss and weight maintenance in overweight or obese adults. Cochrane.Database.Syst.Rev. 2012;12:CD008650. PubMed
  160. Sakamoto, O., Saita, N., Yamasaki, H., Tamanoi, M., and Ando, M. Pulmonary granulomatosis caused by aspirated green tea. Chest 1994;106(1):308-309. PubMed
  161. Jiménez-Encarnación E, Ríos G, Muñoz-Mirabal A, Vilá LM. Euforia-induced acute hepatitis in a patient with scleroderma. BMJ Case Rep 2012;2012. PubMed
  162. Choi JS, Burm JP. Effects of oral epigallocatechin gallate on the pharmacokinetics of nicardipine in rats. Arch Pharm Res. 2009 Dec;32(12):1721-5. PubMed
  163. Chung JH, Choi DH, Choi JS. Effects of oral epigallocatechin gallate on the oral pharmacokinetics of verapamil in rats. Biopharm Drug Dispos. 2009 Mar;30(2):90-3. PubMed
  164. Crew KD, Brown P, Greenlee H, Bevers TB, Arun B, Hudis C, McArthur HL, Chang J, Rimawi M, Vornik L, Cornelison TL, Wang A, Hibshoosh H, Ahmed A, Terry MB, Santella RM, Lippman SM, Hershman DL. Phase IB randomized, double-blinded, placebo-controlled, dose
  165. Dryden GW, Lam A, Beatty K, Qazzaz HH, McClain CJ. A pilot study to evaluate the safety and efficacy of an oral dose of (-)-epigallocatechin-3-gallate-rich polyphenon E in patients with mild to moderate ulcerative colitis. Inflamm Bowel Dis. 2013 Aug;19(9 PubMed
  166. Gallo E, Maggini V, Berardi M, Pugi A, Notaro R, Talini G, Vannozzi G, Bagnoli S, Forte P, Mugelli A, Annese V, Firenzuoli F, Vannacci A. Is green tea a potential trigger for autoimmune hepatitis? Phytomedicine. 2013 Oct 15;20(13):1186-9. PubMed
  167. Liu K, Zhou R, Wang B, Chen K, Shi LY, Zhu JD, Mi MT. Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr. 2013 Aug;98(2):340-8. PubMed
  168. Onakpoya I, Spencer E, Heneghan C, Thompson M. The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis. 2014 Aug;24:823-36. PubMed
  169. Patel SS, Beer S, Kearney DL, Phillips G, Carter BA. Green tea extract: a potential cause of acute liver failure. World J Gastroenterol. 2013 Aug 21;19(31):5174-7. PubMed
  170. Pillukat MH, Bester C, Hensel A, Lechtenberg M, Petereit F, Beckebaum S, Müller KM, Schmidt HH. Concentrated green tea extract induces severe acute hepatitis in a 63-year-old woman--a case report with pharmaceutical analysis. J Ethnopharmacol. 2014 Aug 8; PubMed
  171. Schönthal AH. Adverse effects of concentrated green tea extracts. Mol Nutr Food Res. 2011 Jun;55(6):874-85. PubMed
  172. Shiraishi M, Haruna M, Matsuzaki M, Ota E, Murayama R, Murashima S. Association between the serum folate levels and tea consumption during pregnancy. Biosci Trends. 2010 Oct;4(5):225-30.
  173. Jang EH, Choi JY, Park CS, Lee SK, Kim CE, Park HJ, Kang JS, Lee JW, Kang JH. Effects of green tea extract administration on the pharmacokinetics of clozapine in rats. J Pharm Pharmacol. 2005 Mar;57(3):311-6. PubMed
  174. Trudel D, Labbé DP, Araya-Farias M, Doyen A, Bazinet L, Duchesne T, Plante M, Grégoire J, Renaud MC, Bachvarov D, Têtu B, Bairati I. A two-stage, single-arm, phase II study of EGCG-enriched green tea drink as a maintenance therapy in women with advanced s
  175. Zheng XX, Xu YL, Li SH, Hui R, Wu YJ, Huang XH. Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2013 Apr;97(4):750-62. PubMed
  176. Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J. Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart. 2013;99(19):1383-9. doi: 10.1136/heartjnl-2013-303950. Re PubMed
  177. Cheng M, Hu Z, Lu X, Huang J, Gu D. Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies. Can J Cardiol. 2014 Apr;30(4):448-54. doi: 10.1016/j.cjca.2013.12.026. Epub 2014 2. Review. PubMed
  178. van der Hoeven N, Visser I, Schene A, van den Born BJ. Severe hypertension related to caffeinated coffee and tranylcypromine: a case report. Ann Intern Med. 2014 May 6;160(9):657-8. doi: 10.7326/L14-5009-8. No abstract available. PubMed
  179. Dixit S, Stein PK, Dewland TA, Dukes JW, Vittinghoff E, Heckbert SR, Marcus GM. Consumption of Caffeinated Products and Cardiac Ectopy. J Am Heart Assoc. 2016 26;5(1). pii: e002503. doi: 10.1161/JAHA.115.002503. PubMed
  180. Health Canada. Health Product Info Watch. October 2016; 5-6. Available at: http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/hpiw-ivps_2016-10-eng.php#a15.
  181. Green Tea Extract-Containing Natural Health Products - Rare Risk of Serious Liver Injury. Recalls & alerts. November 15, 2017. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/65100a-eng.php. Accessed November 10, 2017.
  182. Mazzanti G, Di Sotto A, Vitalone A. Hepatotoxicity of green tea: an update. Arch Toxicol. 2015;89(8):1175-91. PubMed
  183. Isomura T, Suzuki S, Origasa H, et al. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. Eur J Clin Nutr. 2016;70(11):1221-1229. PubMed
  184. Drug Record: Green Tea (Camellia Sinesis). LiverTox: National Institutes of Health, U.S. Department of Health & Human Services, March 2014. https://livertox.nlm.nih.gov//GreenTea.htm. Accessed November 20, 2017.
  185. Yates AA, Erdman JW Jr, Shao A, Dolan LC, Griffiths JC. Bioactive nutrients - Time for tolerable upper intake levels to address safety. Regul Toxicol Pharmacol. 2017;84:94-101. PubMed
  186. Younes M, Aggett P, Aguilar F, et al. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Scientific opinion on the safety of green tea catechins. EFSA Journal 2018;16(4):5239. PubMed
  187. Zuchinali P, Riberio PA, Pimentel M, da Rosa PR, Zimerman LI, Rohde LE. Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies. Europace 2016 Feb;18(2):257-66. PubMed
  188. Dostal AM, Samavat H, Bedell S, et al. The safety of green tea extract supplementation in postmenopausal women at risk for breast cancer: results of the Minnesota Green Tea Trial. Food Chem Toxicol. 2015 Sep;83:26-35. PubMed
  189. Shamekhi Z, Amani R, Habibagahi Z, Namjoyan F, Ghadiri A, Saki Malehi A. A Randomized, Double-blind, Placebo-controlled Clinical Trial Examining the Effects of Green Tea Extract on Systemic Lupus Erythematosus Disease Activity and Quality of Life. Phytoth PubMed
  190. Lagier D, Nee L, Guieu R, et al. Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: a randomized controlled clinical trial. Eur J Anaesthesiol. 2018 Apr 26. [Epub ahead of DOI
  191. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  192. Chong SJ, Howard KA, Knox C. Hypokalaemia and drinking green tea: a literature review and report of 2 cases. BMJ Case Rep. 2016;2016. pii: bcr2016214425. PubMed
  193. Qiao J, Gu C, Shang W, et al. Effect of green tea on pharmacokinetics of 5-fluorouracil in rats and pharmacodynamics in human cell lines in vitro. Food Chem Toxicol. 2011;49(6):1410-5. PubMed
  194. Abe O, Ono T, Sato H, et al. Role of (-)-epigallocatechin gallate in the pharmacokinetic interaction between nadolol and green tea in healthy volunteers. Eur J Clin Pharmacol 2018;74(6):775-83. doi: 10.1007/s00228-018-2436-2. PubMed
  195. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648. PubMed
  196. Nutescu EA, Shapiro NL, Ibrahim S, et al. Warfarin and its interactions with foods, herbs and other dietary supplements. Expert Opin Drug Saf. 2006;5(3):433-51. PubMed
  197. Abdelkawy KS, Abdelaziz RM, Abdelmageed AM, Donia AM, El-Khodary NM. Effects of green tea extract on atorvastatin pharmacokinetics in healthy volunteers. Eur J Drug Metab Pharmacokinet. 2020;45(3):351-360. PubMed
  198. Filippini T, Malavolti M, Borrelli F, et al. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Rev. 2020;3(3):CD005004. PubMed
  199. Huang S, Xu Q, Liu L, et al. Effect of green tea and (-)-epigallocatechin gallate on the pharmacokinetics of rosuvastatin. Curr Drug Metab. 2020. PubMed
  200. Mahmoodi M, Hosseini R, Kazemi A, Ofori-Asenso R, Mazidi M, Mazloomi SM. Effects of green tea or green tea catechin on liver enzymes in healthy individuals and people with nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomiz
  201. Misaka S, Abe O, Ono T, et al. Effects of single green tea ingestion on pharmacokinetics of nadolol in healthy volunteers. Br J Clin Pharmacol. 2020. PubMed
  202. Oketch-Rabah HA, Roe AL, Rider CV, et al. United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts. Toxicol Rep. 2020;7:386-402. PubMed
  203. Kim TE, Ha N, Kim Y, et al. Effect of epigallocatechin-3-gallate, major ingredient of green tea, on the pharmacokinetics of rosuvastatin in healthy volunteers. Drug Des Devel Ther. 2017;11:1409-1416. PubMed
  204. Misaka S, Ono Y, Uchida A, et al. Impact of green tea catechin ingestion on the pharmacokinetics of lisinopril in healthy volunteers. Clin Transl Sci. 2020. PubMed
  205. Darweesh RS, El-Elimat T, Zayed A, et al. The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats. BMC Pharmacol Toxicol. 2020;21(1):77. PubMed
  206. Sonoda J, Ogata K, Yoshikawa N, Sato K, Ikeda R, Shimodozono Y. Impact of green tea intake on the pharmacokinetics of celiprolol in healthy subjects. Int J Clin Pharmacol Ther. 2020. PubMed
  207. Kim S, Park TH, Kim WI, Park S, Kim JH, Cho MK. The effects of green tea on acne vulgaris: A systematic review and meta-analysis of randomized clinical trials. Phytother Res. 2021;35(1):374-383. PubMed
  208. Percevault S, Charpiat B, Lebossé F, Mabrut JY, Vial T, Colom M. Green tea and hepatoxicity: Two case reports. Therapie 2021. PubMed
  209. Kajita N, Miyama S, Kinoshita K, Yoshida K, Narita M. Green tea-induced anaphylaxis: The first pediatric case report. Allergol Int 2021;70(4):507-508. PubMed
  210. Zheng KH, Zhu K, Wactawski-Wende J, et al. Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative. Int J Cancer 2021;149(12):2032-2044. PubMed
  211. Wang S, Li X, Yang Y, et al. Does coffee, tea and caffeine consumption reduce the risk of incident breast cancer? A systematic review and network meta-analysis. Public Health Nutr 2021;24(18):6377-6389. PubMed
  212. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Saudi Med J 2021;42(2):151-160. PubMed
  213. Gleason JL, Sundaram R, Mitro SD, et al. Association of maternal caffeine consumption during pregnancy with child growth. JAMA Netw Open. 2022;5(10):e2239609. PubMed
  214. Seufferlein T, Ettrich TJ, Menzler S, et al. Green tea extract to prevent colorectal adenomas, results of a randomized, placebo-controlled clinical trial. Am J Gastroenterol 2022;117(6):884-894. PubMed
  215. Teramoto M, Yamagishi K, Muraki I, Tamakoshi A, Iso H. Coffee and green tea consumption and cardiovascular disease mortality among people with and without hypertension. J Am Heart Assoc 2023;12(2):e026477. PubMed
  216. Veerman GDM, van der Werff SC, Koolen SLW, et al. The influence of green tea extract on nintedanib's bioavailability in patients with pulmonary fibrosis. Biomed Pharmacother 2022;151:113101. PubMed
  217. Misaka S, Ono Y, Taudte RV, et al. Exposure of fexofenadine, but not pseudoephedrine, is markedly decreased by green tea extract in healthy volunteers. Clin Pharmacol Ther 2022;112(3):627-634. PubMed
  218. Zhao H, Zhu W, Zhao X, et al. Efficacy of epigallocatechin-3-gallate in preventing dermatitis in patients with breast cancer receiving postoperative radiotherapy: A double-blind, placebo-controlled, phase 2 randomized clinical trial. JAMA Dermatol 2022;15 PubMed
  219. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed

See these in context on the Green Tea monograph →

Bitter Orange 47 references
  1. Penzak SR, Jann MW, Cold JA, et al. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol 2001;41:1059-63. PubMed
  2. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
  3. Calapai G, Firenzuoli F, Saitta A, et al. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: A preliminary report. Fitoterapia 1999;70:586-92. DOI
  4. Keogh AM, Baron DW. Sympathomimetic abuse and coronary artery spasm. Br Med J 1985;291:940.
  5. Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther 2001;69:14-23. PubMed
  6. Pellati F, Benvenuti S, Melegari M, Firenzuoli F. Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. var. amara by LC. J Pharm Biomed Anal 2002;29:1113-9. . PubMed
  7. Colker CM, Kalman DS, Torina GC, et al. Effects of Citrus aurantium extract, caffeine, and St. John's wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res 1999;60:145-153. DOI
  8. Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol 2002;42:1165-70. PubMed
  9. Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44. PubMed
  10. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60. PubMed
  11. Visentin V, Morin N, Fontana E, et al. Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases. J Pharmacol Exp Ther 2001;299:96-104.
  12. Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother 2004;38:812-6. PubMed
  13. Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: Current status of clinical and basic Research. Exp Biol Med 2004;229:698-704.
  14. Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979;35:1283-4. PubMed
  15. Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin Proc 2004;79:1059-62.. PubMed
  16. Firenzuoli F, Gori L, Galapai C. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine 2005;12:247-8. PubMed
  17. Bouchard NC, Howland MA, Greller HA, et al. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc 2005;80:541-5. PubMed
  18. Haller CA, Benowitz NL, Jacob P 3rd. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 2005;118:998-1003.. PubMed
  19. Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate effects following a single dose of bitter orange. Ann Pharmacother 2006;40:53-7. PubMed
  20. Min B, Cios D, Kluger J, White CM. Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects. Pharmacotherapy 2005;25:1719-24. PubMed
  21. Gange CA, Madias C, Felix-Getzik EM, et al. Variant angina associated with bitter orange in a dietary supplement. Mayo Clin Proc 2006;81:545-8. PubMed
  22. Jordan S, Murty M, Pilon K. Products containing bitter orange or synephrine: suspected cardiovascular adverse reactions. Canadian Adverse Reaction Newsletter 2004;14:3-4.
  23. Burke J, Seda G, Allen D, Knee TS. A case of severe exercise-induced rhabdomyolysis associated with a weight loss dietary supplement. Mil Med 2007;172:656-8. PubMed
  24. Gray, S. and Woolf, A. D. Citrus aurantium used for weight loss by an adolescent with anorexia nervosa. J Adolesc.Health 2005;37(5):414-415. PubMed
  25. Haller, C. A., Duan, M., Jacob, P., III, and Benowitz, N. Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. Br J Clin Pharmacol 2008;65(6):833-840. PubMed
  26. Thomas, J. E., Munir, J. A., McIntyre, P. Z., and Ferguson, M. A. STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature. Tex.Heart Inst.J 2009;36(6):586-590.
  27. Campbell-Tofte, J. I., Molgaard, P., Josefsen, K., Abdallah, Z., Hansen, S. H., Cornett, C., Mu, H., Richter, E. A., Petersen, H. W., Norregaard, J. C., and Winther, K. Randomized and double-blinded pilot clinical study of the safety and anti-diabetic ef
  28. Seifert, J. G., Nelson, A., Devonish, J., Burke, E. R., and Stohs, S. J. Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans. Int J Med Sci 2011;8(3):192-197. PubMed
  29. Stohs, S. J., Preuss, H. G., Keith, S. C., Keith, P. L., Miller, H., and Kaats, G. R. Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med
  30. Wason, S., DiGiacinto, J. L., and Davis, M. W. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther 2012;34(10):2161-2173. PubMed
  31. Kaats, G. R., Miller, H., Preuss, H. G., and Stohs, S. J. A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract. Food Chem Toxicol. 2013;55:358-362.
  32. Calapai, G., Firenzuoli, F., Saitta, A., Squadrito, F. R., Arlotta, M., Costantino, G., and Inferrera, G. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. Fitoterapia 12-1-1999;70(6):586-592. DOI
  33. Colker, C., Kalman, D., and Torina, G. Effects of Citrus aurantium extract, caffeine, and St. John's Wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res 1999;60:145-153. DOI
  34. Shara M, Stohs SJ. Safety evaluation of Bitter orange extract (p-synephrine) in healthy volunteers. J.Amer.Coll.Nutr. 2011;30:358.
  35. Lynch B. Review of the safety of p-synephrine and caffeine. Intertek-Cantox Report, 2013;1-20.
  36. Smith TB, Staub BA, Natarajan GM, et al. Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium. Tex Heart Inst J 2014;41(1):70-2. PubMed
  37. Shara M, Stohs SJ, Mukattash TL. Cardiovascular safety of oral p-synephrine (bitter orange) in healthy subjects: a randomized placebo-controlled cross-over clinical trial. Phytother Res. 2016;30(5):842-7.
  38. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. PubMed
  39. Abdelkawy KS, Donia AM, Turner RB, Elbarbry F. Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects. Drugs R D. 2016 Sep;16(3):271-278. PubMed
  40. Gutiérrez-Hellín J, Salinero JJ, Abían-Vicen J, Areces F, Lara B, Gallo C, et al. Acute consumption of p-synephrine does not enhance performance in sprint athletes.J. Appl Physiol Nutr Metab. 2016;41(1):63-9. doi: 10.1139/apnm-2015-0299.
  41. Jung YP, Earnest CP, Koozehchian M, et al. Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males. J Int Soc Sports Nutr. 2017;3;14:1. doi: 10.1186/s12970-016-0158- PubMed
  42. Jung YP, Earnest CP, Koozehchian M, et al. Effects of acute ingestion of a pre-workout dietary supplement with and without synephrine on resting energy expenditure, cognitive function and exercise performance. J Int Soc Sports Nutr. 2017;14:3. doi: 10.118
  43. Vatsavai LK, Kilari EK. Interaction of p-synephrine on the pharmacodynamic and pharmacokinetics of gliclazide in animal models. J Ayurveda Integr Med 2017; S0975-9476(16)30487-9. doi: 10.1016/j.jaim.2017.04.010.
  44. Ratamess NA, Bush JA, Stohs SJ, et al. Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study. Phytother Res. 2018;32(1):94-102.
  45. Gutiérrez-Hellín J, Ruiz-Moreno C, Del Coso J. Acute p-synephrine ingestion increases whole-body fat oxidation during 1-h of cycling at Fatmax. Eur J Nutr. 2019 Nov 5. PubMed
  46. Karimzadeh Z, Azizzadeh Forouzi M, Tajadini H, Ahmadinejad M, Roy C, Dehghan M. Effects of lavender and Citrus aurantium on pain of conscious intensive care unit patients: a parallel randomized placebo-controlled trial. J Integr Med 2021:S2095-4964(21)000 PubMed
  47. Koncz D, Tóth B, Bahar MA, Roza O, Csupor D. The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis. Nutrients 2022;14(19):4019. PubMed

See these in context on the Bitter Orange 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