Major interaction on record — check this product against your medications before combining. Based on 14 of 16 ingredients. Check your meds →
Dietary supplement

LeanFire PM Ingredients & Drug Interactions

by Force Factor

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

First and foremost: checking LeanFire PM against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Major

LeanFire PM is a dietary supplement by Force Factor 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, 1,768 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Melatonin, Green Tea Leaf Extract, Valerian Root Extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against LeanFire PM by Force Factor

Ask about any prescription or over-the-counter medication and we check it for interactions with LeanFire PM by Force Factor — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of LeanFire PM by Force Factor

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

From our pharmacy team — supplement deep dive

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

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 5 of its 16 active ingredients.
  • “Overnight Burn and Revitalize Complex” is a proprietary blend — the label gives one combined amount (1,091 mg) without saying how much of each component you get.

LeanFire PM contains 16 active and inactive ingredients designed to support nighttime fat metabolism and sleep. The active ingredients include Vitamin B6, Zinc, Vitamin D, L-Tryptophan, Melatonin, L-Theanine, L-Carnitine Tartrate, Chromium, Green Tea Leaf Extract, Lemon Balm Leaf Extract, Valerian Root Extract, Griffonia simplicifolia Seed Extract (which contains 5-HTP), Green Coffee Bean Extract, Hops Flower Extract, plus a proprietary Overnight Burn and Revitalize Complex and Sinetrol.

Inactive ingredients are hypromellose, dicalcium phosphate, magnesium stearate, and silicon dioxide.

Does it work?

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

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

Why this rating?
  • The label markets this product for: nighttime fat burner for sleep and weight loss.
  • We looked for evidence on: Anxiety, Weight management, Metabolic support, Sleep quality.
  • The strongest evidence on file: Melatonin is rated "Possibly Effective" for Pre-procedural anxiety (Natural Medicines).
  • Also on file: L-tryptophan is rated "Insufficient Reliable Evidence To Rate" for Anxiety.
  • Also on file: Lemon Balm is rated "Insufficient Reliable Evidence To Rate" for Anxiety.

The individual ingredients in LeanFire PM have varying levels of evidence. Vitamin B6 is effective for B6 deficiency and sideroblastic anemia, and possibly effective for reducing pregnancy nausea.

Zinc is effective for zinc deficiency. Vitamin D is effective for rickets, osteomalacia, and several bone-related conditions.

L-Tryptophan is possibly ineffective for depression. Melatonin is likely effective for delayed sleep-phase syndrome and non-24-hour sleep disorders, and possibly effective for pre-procedural anxiety.

L-Theanine is possibly effective for cognitive function. L-Carnitine is effective for carnitine deficiency and possibly effective for heart conditions.

Chromium is likely effective for chromium deficiency and possibly effective for diabetes. Green Tea Leaf Extract is likely effective for human papillomavirus (HPV) and possibly effective for cholesterol levels.

Lemon Balm is possibly effective for cold sores, stress, and depression. Valerian is possibly effective for insomnia.

Griffonia simplicifolia has insufficient evidence for anxiety, depression, and other conditions. Green Coffee Bean Extract is likely effective for mental alertness and possibly effective for Parkinson disease and heart conditions.

Hops has insufficient evidence for most conditions. We hold no effectiveness data for the proprietary blend, Sinetrol, or White Kidney Bean Seed Extract.

The evidence, ingredient by ingredient Vitamin B6 Zinc Vitamin D Chromium L-tryptophan Melatonin Theanine L-carnitine

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 14 of the 14 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 14 of 14.
  • General safety write-ups exist for 14 of 14.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients in LeanFire PM are generally well tolerated at recommended doses, but several warrant caution. Vitamin B6 is safe at normal food and supplement levels; however, very high doses over time can damage nerves (sensory neuropathy).

Zinc is well tolerated below 40 mg daily; higher doses long-term may increase copper deficiency risk. Vitamin D is safe at recommended doses but very high doses can cause toxicity with symptoms like high blood calcium.

L-Tryptophan caused a serious contamination scare in 1989 (eosinophilia-myalgia syndrome) linked to a single Japanese manufacturer; modern supplies are considered safer, though it may cause drowsiness, nausea, and other common side effects. Melatonin is generally well tolerated short-term but long-term safety is less certain; rare concerns include seizure risk and mood changes.

L-Theanine may cause headaches and drowsiness. L-Carnitine can cause gastrointestinal upset and a fish-like body odor; rare cases of seizures have been reported.

Chromium is well tolerated at typical doses but high doses carry rare risks of kidney and liver damage. Green Tea Leaf Extract is safe as a beverage but concentrated extracts in high doses have rarely caused liver injury.

Lemon Balm, Valerian, and Griffonia simplicifolia all have limited long-term safety data. Hops generally causes no serious effects short-term but may cause drowsiness.

No pregnancy or breastfeeding safety data are on file for most ingredients in this product.

Side effects, ingredient by ingredient Vitamin B6 Zinc Vitamin D Chromium L-tryptophan Melatonin Theanine L-carnitine

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?
  • 14 of the 14 matched ingredients can interact with medications — L-tryptophan, Lemon Balm, Hops, Valerian, Vitamin D, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,769 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 LeanFire PM, double-check your exact medications against these drug types: Major concerns are beta-blockers like nadolol, ephedrine, and statins like atorvastatin (green tea); Moderate concerns include blood pressure medications, seizure medications (phenytoin, phenobarbital), antibiotics (quinolones, tetracyclines, cephalexin), HIV medications, heart rhythm drugs (digoxin, diltiazem, verapamil), blood thinners (warfarin), diabetes medications, thyroid medications, antidepressants, pain medications (especially MAOIs, tramadol, meperidine), sedatives, and caffeine-sensitive drugs like clozapine and lamotrigine. No interactions are documented for Sinetrol, White Kidney Bean Seed Extract, or the proprietary blend.

Check your own medication Run your meds through the checker above

The bottom line

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

LeanFire PM is a multi-ingredient nighttime supplement with support for sleep and metabolism—but it's not right for everyone. If you take prescription medications, especially beta-blockers, seizure drugs, blood thinners, diabetes medications, heart rhythm drugs, or antibiotics, you need to check your specific list with a pharmacist before starting.

Talk to your pharmacist before using this product, particularly if you're pregnant, breastfeeding, or have any chronic health conditions.

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

Assessment coverage: 14 of 16 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jun 25, 2025.

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 LeanFire PM, straight from the product label.

Brand Force Factor
Net contents 60 Vegetable Capsule(s)
Market status On market
Date entered into DSLD Jun 25, 2025
DSLD ID 336123
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Sugar Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for LeanFire PM by Force Factor, 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 Vegetable Capsule(s)
Maximum serving Sizes:
2 Vegetable Capsule(s)
Servings per container
30
IngredientAmount% DV
Vitamin B65 mg294%
Zinc12 mg109%
Vitamin D84 mcg420%
L-Tryptophan0 NP--
Melatonin1 mg--
L-Theanine0 NP--
L-Carnitine Tartrate0 NP--
Chromium100 mcg286%
Green Tea Leaf Extract0 NP--
Lemon Balm Leaf Extract0 NP--
Valerian Root Extract0 NP--
Griffonia simplicifolia Seed Extract0 NP--
Green Coffee Bean Extract0 NP--
Hops Flower Extract0 NP--
Overnight Burn and Revitalize Complex1091 mg--
Sinetrol0 NP--
White Kidney Bean Seed Extract0 NP--

Other ingredients: Hypromellose, Dicalcium Phosphate, Magnesium Stearate, Silicon Dioxide

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.
Formulation

A new kind of fat burner Your metabolism and sleep cycle are interdependent; studies have shown that a lack of quality sleep can lead to overeating and weight gain, which means taking stimulant-based fat burners later in the day can be counterproductive, LeanFire PM was was engineered to stack with your favorite daytime thermo to help you burn fat overnight, meaning reaching your weight loss goals can happen even more quickly. This formula is stimulant-free, combining the latest innovations in both sleep and fat burning science so you can achieve restful sleep while simultaneously burning calories. If you are looking for a powerful nighttime fat burner to add to your weight loss stack, look no further than LeanFire PM. You deserve a formula that works with your sleep schedule to help deliver round-the-clock results.

This formula is stimulant-free, combining the latest innovations in both sleep and fat burning science so you can achieve restful sleep while simultaneously burning calories.

Nighttime fat burner Burn fat overnight Support weight loss Boost resting metabolism Improve relaxation and sleep

Ingredients you can trust No artificial colors No artificial flavors No gelatin No sugar No artificial sweeteners No preservatives

Suggested/Recommended/Usage/Directions

Directions Take 2 capsules daily 30-45 minutes before bed.

Formula

Featuring Sinetrol

FDA Statement of Identity

Dietary Supplement

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

See for yourself

LeanFire PM by Force Factor label

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

LeanFire PM label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in LeanFire PM by Force Factor

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

Serving size2 Vegetable Capsule(s) Dosage formCapsule Servings per container30 Amounts shown are per serving.

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

Vitamin B6

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

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

Vitamin B6 monograph & interactions

Zinc

Interacts with
67 drugs
12 mg per serving Form: Zinc Oxide

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

Vitamin D

Interacts with
715 drugs
84 mcg per serving Form: Cholecalciferol

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people,...

Vitamin D monograph & interactions

Chromium

Interacts with
178 drugs
100 mcg per serving Form: Chromax

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

Overnight Burn and Revitalize Complex

1091 mg per serving

Other (inactive) ingredients: Hypromellose, Dicalcium Phosphate, Magnesium Stearate, Silicon Dioxide. These complete the product’s ingredient list but are not active constituents.

Interaction report

LeanFire PM by Force Factor Drug Interactions

Want to check YOUR meds against LeanFire PM?

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
1,768Drugs
256 Major 1,323 Moderate 189 Minor

Ingredients driving the most interactions

Melatonin 1,461
Green Tea Leaf Extract 1,293
Valerian Root Extract 902
Hops Flower Extract 863
Vitamin D 715

Individual Drug Interactions

The ingredients in LeanFire PM interact with 1,768 drugs. Click any drug to see the details.

14 of the 16 ingredients in LeanFire PM interact with drugs. Each result below shows which ingredient is responsible. Melatonin Green Tea Leaf Extract Valerian Root Extract Hops Flower Extract Vitamin D Green Coffee Bean Extract L-Theanine L-Tryptophan Griffonia simplicifolia Seed Extract Lemon Balm Leaf Extract Vitamin B6 Chromium Zinc L-Carnitine Tartrate

Each ingredient & the kinds of drugs it affects

For each ingredient in LeanFire PM 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.

Melatonin18 drug types · 1,461 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There are isolated case reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin). The mechanism, if any, of this interaction is unknown. Taking melatonin orally seems to decrease coagulation activity within one hour of dosing in healthy men.

Likelihood Possible Evidence B
Anticonvulsants

Theoretically, melatonin may reduce the effects of anticonvulsants. Some clinical research suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological impairment.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking melatonin with antidiabetes drugs might increase the risk of hypoglycemia.
Some clinical research shows that melatonin reduces levels of fasting blood glucose and improves glycemic control. However, other research suggests that melatonin might impair glucose utilization and increase insulin resistance, while other research has found no effect on glucose levels. Until more is known, use melatonin cautiously in combination with antidiabetes drugs.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking melatonin with antihypertensive drugs might increase the risk of hypotension or hypertension.
Some clinical research suggests that taking melatonin decreases blood pressure in healthy adults. Also, melatonin seems to lower systolic and diastolic blood pressure in individuals with high blood pressure at nighttime or untreated essential hypertension. However, melatonin seems to worsen blood pressure in patients who are taking antihypertensive medications. Immediate-release melatonin 5 mg at night in combination with nifedipine GITS (Procardia XL) increases systolic blood pressure an average of 6.5 mmHg, diastolic blood pressure by an average of 4.9 mmHg, and heart rate by 3.9 bpm. Also, results from animal research suggest that melatonin reduces the effectiveness of certain antihypertensive drugs, including methoxamine and clonidine.

Likelihood Possible Evidence A
Caffeine

Theoretically, taking caffeine with melatonin might increase levels of melatonin.
Some evidence suggests that caffeine consumption can decrease endogenous melatonin levels, while other evidence suggests that caffeine increases endogenous melatonin levels. When administered in combination with melatonin supplements, caffeine seems to increase melatonin effects and levels. The reason for this discrepancy is not completely clear. Part of the discrepancy may result from the fact that caffeine can inhibit melatonin synthesis as well as inhibit melatonin metabolism. By functioning as an adenosine receptor antagonist, caffeine may indirectly inhibit the synthesis of melatonin. Conversely, because melatonin and caffeine are both metabolized by cytochrome P450 1A2 (CYP1A2) enzyme, concomitant use of melatonin and caffeine may reduce the metabolism of melatonin, resulting in higher serum levels.

Likelihood Probable Evidence B
Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.
Melatonin has sedative effects. Theoretically, concomitant use of melatonin with alcohol, benzodiazepines, or other sedative drugs might cause additive sedation.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, taking contraceptive drugs with melatonin might increase the effects and adverse effects of melatonin.
Contraceptive drugs can increase the levels of endogenous melatonin. Theoretically, these drugs may increase the effects and adverse effects of oral melatonin.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2. Also, other CYP1A2 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with drugs metabolized by the CYP1A2 enzyme might reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP2C19. Also, other CYP2C19 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2C19 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP2C19 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

Theoretically, taking fluvoxamine with melatonin might increase levels of melatonin.
Fluvoxamine can significantly increase melatonin levels. In some cases, fluvoxamine might increase bioavailability of exogenously administered melatonin by up to 20 times. Some researchers think this might be a beneficial interaction and be potentially useful for cases of refractory insomnia. However, this interaction might also cause unwanted excessive drowsiness and possibly other adverse effects. Fluvoxamine is known to increase endogenous melatonin secretion. It seems to increase serum levels of exogenously administered melatonin possibly by decreasing melatonin metabolism by inhibiting cytochrome P450 (CYP450) 1A2 and 2C19 or by inhibiting melatonin elimination. This effect has been found in healthy people taking fluvoxamine 50-75 mg and melatonin 5 mg.

Likelihood Probable Evidence B
Immunosuppressants

Theoretically, melatonin might interfere with immunosuppressive therapy.
Melatonin can stimulate immune function. Theoretically, melatonin might interfere with immunosuppressive therapy.

Likelihood Possible Evidence B
Methamphetamine (Desoxyn)

Theoretically, taking melatonin with methamphetamine may increase the adverse effects of methamphetamine.
Animal research suggests that melatonin exacerbates the adverse effects of methamphetamine, resulting in greater depression of tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activity, as well as a significant reduction in dopamine levels. This has not been shown in humans.

Likelihood Possible Evidence D
Nifedipine Gits (Procardia Xl)

Theoretically, taking melatonin with extended release nifedipine reduces the effects of nifedipine.
Melatonin can decrease the effectiveness of extended release nifedipine (GITS). Immediate-release melatonin 5 mg at night in combination with nifedipine GITS 30-60 mg daily increases systolic and blood pressure by an average of 6.5 mmHg and 4.9 mmHg, respectively. Concomitant use with melatonin also increases heart rate by 3.9 bpm. The mechanism of this interaction is not known.

Likelihood Probable Evidence B
Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.
Some clinical evidence suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological disabilities.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, melatonin may have antiplatelet effects and may increase the risk of bleeding with warfarin.
Three cases of increased prothrombin time have been reported for patients aged 48-72 years who took melatonin orally in combination with warfarin. However, three cases of decreased prothrombin time have also been reported for patients aged 51-84 years who took melatonin orally in combination with warfarin. Until more is known, use melatonin cautiously in patients taking warfarin.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP2D6.
Laboratory research suggests that certain lots of melatonin inhibit CYP2D6. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2D6 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that certain lots of melatonin inhibit CYP3A4. Theoretically, combined administration of melatonin with certain drugs metabolized by CYP3A4 may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Possible Evidence D
Flumazenil (Romazicon)

Theoretically, taking flumazenil with melatonin might reduce the effects of melatonin.
Animal research shows that flumazenil may inhibit the effect of melatonin.

Likelihood Possible Evidence D
Melatonin full monograph & interactions

Green Tea Leaf Extract58 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
Green Tea Leaf Extract full monograph & all 58 interactions

Valerian Root Extract6 drug types · 902 drugs

Alcohol (Ethanol)

Valerian can have additive sedative effects when used concomitantly with alcohol.
Valerian has sedative effects. Theoretically, valerian might have an additive sedative effect when combined with alcohol. Excessive sedation has been reported in an alcohol-abusing individual who took valerian and Gingko biloba. However, the potential interaction between valerian and alcohol has been disputed in other research. Limited evidence suggests that a combination of valerian 160 mg and lemon balm 80 mg (Euvegal) does not cause further deterioration in reaction ability and reaction rate when taken with alcohol as compared to the effects of alcohol alone.

Likelihood Possible Evidence B
Alprazolam (Xanax)

Valerian can have additive sedative effects when used with alprazolam. Also, valerian in high doses might modestly increase alprazolam levels, though this is not likely to be clinically significant.
Valerian has sedative effects. Theoretically, valerian might cause additive sedation when combined with alprazolam. Also, a small pharmacokinetic study shows that taking valerian extract 1000 mg daily (providing 11 mg valerenic acid) might increase alprazolam levels by about 19%. This might be due to valerian's mild inhibition of cytochrome P450 3A4 (CYP3A4). Despite being statistically significant, this increase is not likely to be clinically significant.

Likelihood Possible Evidence B
Cns Depressants

Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
Theoretically, concomitant use of valerian and drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.

Likelihood Possible Evidence D
Glucuronidated Drugs

Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.
In vitro research shows that methanolic valerian extract and valerenic acid might competitively inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) and UGT2B7.

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP2D6.
Although some in vitro evidence suggests that valerian affects CYP2D6, clinical pharmacokinetic (PK) studies show that valerian is unlikely to affect the CYP2D6 enzyme. In one PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days did not affect the metabolism of dextromethorphan, a CYP2D6 substrate. In another PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of debrisoquine, an accepted CYP2D6 probe-substrate.

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP3A4.
Although some in vitro evidence suggests that valerian extract might inhibit or induce CYP3A4, clinical pharmacokinetic (PK) studies show that valerian does not have a clinically significant effect on the CYP3A4 enzyme. In one PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of midazolam, an accepted CYP3A4 probe-substrate. In another PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days modestly increases levels of alprazolam, a CYP3A4 substrate, suggesting mild inhibition of CYP3A4. However, this mild inhibition is unlikely to be clinically relevant.

Likelihood Possible Evidence B
Valerian Root Extract full monograph & interactions

Hops Flower Extract4 drug types · 863 drugs

Cns Depressants

Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.
Some animal research shows that hops has sedative effects.

Likelihood Possible Evidence D
Estrogens

Theoretically, concomitant use of large amounts of hops might interfere with hormone replacement therapy due to competition for estrogen receptors.
In vitro research suggests that certain hops constituents can competitively bind to estrogen receptors. However, most hops extracts contain very small amounts of these constituents.

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

Hops extract does not seem to affect the metabolism of CYP1A2 substrates.
In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate.

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

Theoretically, hops extract might alter metabolism of CYP3A4 substrates; however, this effect may not be clinically significant.
Animal research suggests that specific constituents of hops, called lupulones, can induce hepatic CYP3A4 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients with normal metabolism shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, decreases the concentration of alprazolam, a CYP3A4 probe substrate, by 7.6%. This reduction is unlikely to be clinically relevant.

Likelihood Possible Evidence D
Hops Flower Extract full monograph & interactions

Vitamin D8 drug types · 715 drugs

Aluminum

Vitamin D might increase aluminum absorption and toxicity, but this has only been reported in people with renal failure.
The protein that transports calcium across the intestinal wall can also bind and transport aluminum. This protein is stimulated by vitamin D, which may therefore increase aluminum absorption. This mechanism may contribute to increased aluminum levels and toxicity in people with renal failure, when they take vitamin D and aluminum-containing phosphate binders chronically.

Likelihood Probable Evidence B
Atorvastatin (Lipitor)

Vitamin D might reduce absorption of atorvastatin.
A small, low-quality clinical study shows that taking vitamin D reduces levels of atorvastatin and its active metabolites by up to 55%. However, while atorvastatin levels decreased, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels did not substantially change. Atorvastatin is metabolized in the gut by CYP3A4 enzymes, and researchers theorized that vitamin D might induce CYP3A4, causing reduced levels of atorvastatin. However, this proposed mechanism was not specifically studied.

Likelihood Probable Evidence B
Calcipotriene (Dovonex)

Taking calcipotriene with vitamin D increases the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with vitamin D supplements might increase the risk of hypercalcemia.

Likelihood Probable Evidence D
Digoxin (Lanoxin)

Theoretically, hypercalcemia induced by high-dose vitamin D can increase the risk of arrhythmia from digoxin.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and digoxin concurrently.

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

Theoretically, hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of diltiazem for arrhythmia.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically this could also occur with diltiazem. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and diltiazem concurrently.

Likelihood Probable Evidence B
Thiazide Diuretics

Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily.

Likelihood Probable Evidence D
Verapamil (Calan, Others)

Hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of verapamil for arrhythmia.
Hypercalcemia due to high doses of vitamin D can reduce the effectiveness of verapamil in atrial fibrillation. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.

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

Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.

Likelihood Possible Evidence D
Vitamin D full monograph & interactions

Green Coffee Bean Extract33 drug types · 591 drugs

Ephedrine

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

Likelihood Probable Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Alendronate (Fosamax)

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

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

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

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

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

Likelihood Probable Evidence D
Cimetidine (Tagamet)

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

Likelihood Likely Evidence B
Clozapine (Clozaril)

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

Likelihood Possible Evidence B
Contraceptive Drugs

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

Likelihood Probable Evidence B
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence B
Lamotrigine (Lamictal)

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

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

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

Likelihood Possible Evidence B
Lithium

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

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence B
Phenylpropanolamine

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

Likelihood Probable Evidence B
Pioglitazone (Actos)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Stimulant Drugs

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

Likelihood Probable Evidence C
Theophylline

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

Likelihood Probable Evidence B
Green Coffee Bean Extract full monograph & all 33 interactions

L-Theanine3 drug types · 565 drugs

Antihypertensive Drugs

Theanine might lower blood pressure, potentiating the effects of antihypertensive drugs.
Animal research shows that theanine can lower blood pressure in spontaneously hypertensive animals. Theoretically, concomitant use of theanine and antihypertensive drugs might potentiate the antihypertensive activity.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, theanine might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Theoretically, theanine may compete with glutamate and/or increase plasma gamma-aminobutyric acid (GABA) levels, which could cause CNS depression. In one clinical study, some subjects taking oral theanine reported drowsiness.

Likelihood Unlikely Evidence D
Serotonergic Drugs

Clinical studies regarding the effects of L-theanine on serotonin levels are conflicting. Some studies suggest it can increase serotonin levels in the brain while others report that it may decrease them. Nevertheless, there have been no reports of l-theanine being a causative agent in serotonergic-related side effects or serotonin syndrome.

Likelihood Unlikely Evidence C
L-Theanine full monograph & interactions

L-Tryptophan2 drug types · 394 drugs

Cns Depressants

Theoretically, concomitant use of L-tryptophan with CNS depressants might cause additive sedative effects.
Clinical research shows that L-tryptophan can cause fatigue and drowsiness.

Likelihood Probable Evidence B
Serotonergic Drugs

Theoretically, combining L-tryptophan with serotonergic drugs might cause additive serotonergic effects.
L-tryptophan is a precursor to serotonin. Theoretically, combining serotonergic drugs with L-tryptophan might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders.

Likelihood Possible Evidence D
L-Tryptophan full monograph & interactions

Griffonia simplicifolia Seed Extract8 drug types · 317 drugs

Antidepressant Drugs

Theoretically, taking Griffonia simplicifolia seed extract with antidepressant drugs might increase the risk of serotonergic adverse effects, such as serotonin syndrome and cerebral vasoconstrictive disorders such as Call-Fleming syndrome.
Griffonia simplicifolia seed extract contains 5-HTP. Taking 5-HTP with antidepressant drugs increases the risk of serotonergic adverse effects.

Likelihood Possible Evidence D
Carbidopa (Lodosyn)

Theoretically, taking Griffonia simplicifolia seed extract with carbidopa might increase the risk of serotonergic and other adverse effects.
Griffonia simplicifolia seed extract contains 5-HTP. Taking 5-HTP with carbidopa increases the risk of serotonergic adverse effects, scleroderma-like skin reactions, hypomania, restlessness, rapid speech, anxiety, insomnia, and aggressiveness.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, taking Griffonia simplicifolia seed extract with CNS depressants might increase the risk of additive CNS depression.
Griffonia simplicifolia seed extract contains 5-HTP. In clinical trials, 5-HTP has been associated with drowsiness and somnolence.

Likelihood Possible Evidence D
Dextromethorphan (Robitussin Dm, Others)

Theoretically, taking Griffonia simplicifolia seed extract with dextromethorphan might increase the risk of serotonergic adverse effects, such as serotonin syndrome and cerebral vasoconstrictive disorders such as Call-Fleming syndrome.
Griffonia simplicifolia seed extract contains 5-HTP. Taking 5-HTP with dextromethorphan increases the risk of serotonergic adverse effects.

Likelihood Possible Evidence D
Meperidine (Demerol)

Theoretically, taking Griffonia simplicifolia seed extract with meperidine might increase the risk of serotonergic adverse effects, such as serotonin syndrome and cerebral vasoconstrictive disorders such as Call-Fleming syndrome.
Griffonia simplicifolia seed extract contains 5-HTP. Taking 5-HTP with meperidine increases the risk of serotonergic adverse effects.

Likelihood Possible Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking Griffonia simplicifolia seed extract with MAOIs might increase the risk of serotonergic adverse effects, such as serotonin syndrome and cerebral vasoconstrictive disorders such as Call-Fleming syndrome.
Griffonia simplicifolia seed extract contains 5-HTP. Taking 5-HTP with MAOIs increases the risk of serotonergic adverse effects.

Likelihood Possible Evidence D
Pentazocine (Talwin)

Theoretically, taking Griffonia simplicifolia seed extract with pentazocine drugs might increase the risk of serotonergic adverse effects, such as serotonin syndrome and cerebral vasoconstrictive disorders such as Call-Fleming syndrome.
Griffonia simplicifolia seed extract contains 5-HTP. Taking 5-HTP with pentazocine increases the risk of serotonergic adverse effects.

Likelihood Possible Evidence D
Tramadol (Ultram)

Theoretically, taking Griffonia simplicifolia seed extract with tramadol might increase the risk of serotonergic adverse effects, such as serotonin syndrome and cerebral vasoconstrictive disorders such as Call-Fleming syndrome.
Griffonia simplicifolia seed extract contains 5-HTP. Taking 5-HTP with tramadol increases the risk of serotonergic adverse effects.

Likelihood Possible Evidence D
Griffonia simplicifolia Seed Extract full monograph & interactions

Lemon Balm Leaf Extract2 drug types · 264 drugs

Cns Depressants

Theoretically, concomitant use of lemon balm might have additive effects with CNS depressant drugs.
Lemon balm seems to have CNS depressant activity in animals and in humans.

Likelihood Possible Evidence B
Thyroid Hormone

Theoretically, lemon balm might interfere with thyroid hormone replacement therapy.
In vitro, constituents of lemon balm extract bind to thyroid stimulating hormone (TSH), preventing TSH receptor-binding and leading to the inhibition of TSH-stimulated adenylate cyclase activity. In animals, lemon balm extract has been shown to decrease levels of circulating TSH and inhibit thyroid secretion.

Likelihood Possible Evidence D
Lemon Balm Leaf Extract full monograph & interactions

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

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

Likelihood Possible Evidence B
Antihypertensive Drugs

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Levodopa

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

Likelihood Unlikely Evidence D
Vitamin B6 full monograph & interactions

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
Chromium full monograph & interactions

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
Zinc full monograph & interactions

L-Carnitine Tartrate3 drug types · 19 drugs

Acenocoumarol (Sintrom)

Theoretically, L-carnitine might increase the anticoagulant effects of acenocoumarol.
L-carnitine might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant similar to warfarin, but shorter-acting. There are at least two case reports of INR elevation with concomitant use. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, L-carnitine might decrease the effectiveness of thyroid hormone replacement.
L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells. Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism.

Likelihood Probable Evidence B
Warfarin (Coumadin)

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

Likelihood Possible Evidence D
L-Carnitine Tartrate full monograph & interactions
The maker

Brand information

Manufacturer and brand details for LeanFire PM, from the product label.

Force Factor

Name
Force Factor
Pharmacist Counseling Corner

LeanFire PM by Force Factor: Common Questions

Does LeanFire PM by Force Factor interact with any medications?
Yes. Based on its ingredients, LeanFire PM has a known interaction with 1,768 medications, including 256 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
LeanFire PM 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 LeanFire PM if I'm on blood pressure medication?
Several ingredients—vitamin B6, melatonin, and L-theanine—may lower blood pressure, potentially adding to your medication's effects. You should check with your pharmacist before starting. The same caution applies if you take heart medications like digoxin or diltiazem.
Will this help me lose weight?
LeanFire PM is marketed for nighttime fat metabolism, but we don't have effectiveness data on file for weight loss. Some ingredients like green coffee bean extract (caffeine) and chromium are possibly effective for metabolic support, but the evidence isn't strong. Talk to your doctor about whether this is right for your weight goals.
What are the most common side effects?
The most common side effects across ingredients include drowsiness, headache, nausea, and gastrointestinal upset (stomach cramps, diarrhea). L-tryptophan may cause dry mouth and lightheadedness. Melatonin can cause dizziness. If you experience any of these, stop and talk to your pharmacist.
Is it safe to take LeanFire PM with my antibiotics?
Probably not at the same time. Zinc in this product can bind to many antibiotics—including tetracyclines, quinolones, and cephalexin—and prevent your body from absorbing them properly. If you're on an antibiotic, take it at least 2–4 hours away from this supplement and check with your pharmacist on exact timing.
Can I take this while pregnant or breastfeeding?
We don't have enough safety data on file for most ingredients in this product during pregnancy or breastfeeding. Some, like L-tryptophan and Griffonia simplicifolia, are advised against. Talk to your doctor or pharmacist before using LeanFire PM if you're pregnant or nursing.
Does this supplement contain caffeine?
Yes—it contains green coffee bean extract, which is a source of caffeine. The label doesn't specify the amount, so if you're sensitive to caffeine or take caffeine-sensitive medications (like clozapine or lamotrigine), mention this to your pharmacist.

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

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

LeanFire PM label
Go deeper

The Full Monographs Behind LeanFire PM’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

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

Vitamin D

Interacts with 715 drugs

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people, especially those with low sun exposure,...

Read the full Vitamin D 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

L-tryptophan

Interacts with 394 drugs

L-tryptophan is an essential amino acid the body uses to make serotonin and melatonin, and people take it to support sleep and mood. The evidence for supplement use is limited and mixed, and...

Read the full L-tryptophan monograph → Herb & supplement monograph

Melatonin

Interacts with 1,461 drugs

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timing problems and jet lag. The evidence is...

Read the full Melatonin monograph → Herb & supplement monograph

Theanine

Interacts with 565 drugs

Theanine (usually L-theanine) is an amino acid found naturally in tea leaves that many people take to feel calmer and less stressed without strong drowsiness. Early research suggests it may...

Read the full Theanine monograph → Herb & supplement monograph

L-carnitine

Interacts with 19 drugs

L-carnitine is a compound your body makes naturally and also gets from foods like meat. It helps cells turn fat into energy, and supplements are most clearly useful for people with a true ca...

Read the full L-carnitine 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

Lemon Balm

Interacts with 264 drugs

Lemon balm is a gentle, lemon-scented mint-family herb traditionally used to ease stress, support sleep, and calm digestion, and topically for cold sores. Early studies are promising but gen...

Read the full Lemon Balm monograph → Herb & supplement monograph

Valerian

Interacts with 902 drugs

Valerian is an herb whose root is widely used as a natural sleep aid and for calming nerves. The evidence is mixed and often weak, so it may help some people sleep but does not work reliably...

Read the full Valerian monograph → Herb & supplement monograph

Griffonia Simplicifolia

Interacts with 317 drugs

Griffonia simplicifolia is a West African shrub whose seeds are a natural source of 5-HTP, a building block of the brain chemical serotonin. Some people use it for mood, sleep, and appetite,...

Read the full Griffonia Simplicifolia monograph → Herb & supplement monograph

Coffee

Interacts with 591 drugs

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

Read the full Coffee monograph → Herb & supplement monograph

Hops

Interacts with 863 drugs

Hops are most often used for sleep and mild anxiety, frequently combined with valerian, but the human evidence is limited and not very strong. They are generally well tolerated when used sho...

Read the full Hops monograph →
Sources

Sources & How We Checked

LeanFire PM'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 862 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 →

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 →

Vitamin D 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  3. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-7. PubMed
  4. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  5. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialyzed patients taking AI(OH)3. Clin Nephrol 1986;26:146-9.
  6. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  7. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  8. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  9. Moon J. The role of vitamin D in toxic metal absorption. J Am Coll Nutr 1994;13:559-64.
  10. Demontis R, Reissi D, Noel C, et al. Indirect clinical evidence that 1alphaOH vitamin D<SUB>3</SUB> increases the intestinal absorption of aluminum. Clin Nephrol 1989;31:123-7.
  11. Adler AJ, Berlyne GM. Duodenal aluminum absorption in the rat: effect of vitamin D. Am J Physiol 1985;249:G209-13. PubMed
  12. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  13. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  14. Cox KA, Dunn MA. Aluminum toxicity alters the regulation of calbindin-D28k protein and mRNA expression in chick intestine. J Nutr 2001;131:2007-13. PubMed
  15. Escribano, J., Balaguer, A., Pagone, F., Feliu, A., and Roque, I. Figuls. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane.Database.Syst.Rev. 2009;(1):CD004754. PubMed
  16. Carlton, S., Clopton, D., and Cappuzzo, K. A. Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. Consult Pharm 2010;25(3):171-177. PubMed
  17. Wang, H., Xia, N., Yang, Y., and Peng, D. Q. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis. 2012;11:42. PubMed
  18. Turner AN, Carr Reese P, Fields KS, Anderson J, Ervin M, Davis JA, Fichorova RN, Roberts MW, Klebanoff MA, Jackson RD. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis. Am J Obstet G PubMed
  19. Weiner M, Epstein FH. Signs and symptoms of electrolyte disorders. Yale J Biol Med. 1970;43(2):76-109.
  20. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  21. Roth DE, Leung M, Mesfin E, Qamar H, Watterworth J, Papp E. Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ. 2017;359:j5237. PubMed
  22. Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: A randomized clinical trial. JAMA. 2021.
  23. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54-8. PubMed
  24. Doyle D, Browne U, Brickley A, Murphy D. Vitamin D-induced hypercalcaemia and acute kidney injury in sarcoidosis. BMJ Case Rep 2023;16(1):e250580. PubMed
  25. Williamson A, Martineau AR, Sheikh A, Jolliffe D, Griffiths CJ. Vitamin D for the management of asthma. Cochrane Database Syst Rev 2023;2(2):CD011511. PubMed
  26. Kinesya E, Santoso D, Gde Arya N, et al. Vitamin D as adjuvant therapy for diabetic foot ulcers: Systematic review and meta-analysis approach. Clin Nutr ESPEN 2023;54:137-143. PubMed

See these in context on the Vitamin D monograph →

L-tryptophan 18 references
  1. Messiha FS. Fluoxetine: adverse effects and drug-drug interactions. J Toxicol Clin Toxicol 1993;31:603-30. PubMed
  2. Devoe LD, Castillo RA, Searle NS. Maternal dietary substrates and human fetal biophysical activity. The effects of tryptophan and glucose on fetal breathing movements. Am J Obstet Gynecol 1986;155:135-9. DOI
  3. Lieberman HR, Corkin S, Spring BJ. The effects of dietary neurotransmitter precursors on human behavior. Am J Clin Nutr 1985;42:366-70. PubMed
  4. U. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. Information Paper on L-Tryptophan and 5-hydroxy-L-tryptophan, February 2001.
  5. Sullivan EA, Kamb ML, Jones JL, et al. The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina. Arch Intern Med 1996;156:973-9. DOI
  6. Philen RM, Hill RH, Flanders WD, et al. Tryptophan contaminants associated with eosinophilia-myalgia syndrome. Am J Epidemiol 1993;138:154-9. PubMed
  7. Bohme A, Wolter M, Hoelzer D. L-tryptophan-related eosinophilia-myalgia syndrome possibly associated with a chronic B-lymphocytic leukemia. Ann Hematol 1998;77:235-8. PubMed
  8. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  9. Priori R, Conti F, Luan FL, et al. Chronic fatigue: a peculiar evolution of eosinophilia myalgia syndrome following treatment with L-tryptophan in four Italian adolescents. Eur J Pediatr 1994;153:344-6..
  10. Klein R, Berg PA. A comparative study on antibodies to nucleoli and 5-hydroxytryptamine in patients with fibromyalgia syndrome and tryptophan-induced eosinophilia-myalgia syndrome. Clin Investig 1994;72:541-9.. PubMed
  11. Simat TJ, Kleeberg KK, Muller B, Sierts A. Synthesis, formation, and occurrence of contaminants in biotechnologically manufactured L-tryptophan. Adv Exp Med Biol 1999;467:469-80.. PubMed
  12. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002;(1):CD003198. PubMed
  13. Kilbourne EM, Philen RM, Kamb ML, Falk H. Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome. J Rheumatol Suppl 1996;46:81-8.
  14. Horwitz RI, Daniels SR. Bias or biology: evaluating the epidemiologic studies of L-tryptophan and the eosinophilia-myalgia syndrome. J Rheumatol Suppl 1996;46:60-72.
  15. Shapiro S. Epidemiologic studies of the association of L-tryptophan with the eosinophilia-myalgia syndrome: a critique. J Rheumatol Suppl 1996;46:44-58.
  16. Mayeno AN, Gleich GJ. The eosinophilia-myalgia syndrome: lessons from Germany. Mayo Clin Proc 1994;69:702-4. PubMed
  17. Carr L, Ruther E, Berg PA, Lehnert H. Eosinophilia-myalgia syndrome in Germany: an epidemiologic review. Mayo Clin Proc 1994;69:620-5. PubMed
  18. Ullrich SS, Fitzgerald PCE, Giesbertz P, Steinert RE, Horowitz M, Feinle-Bisset C. Effects of intragastric administration of tryptophan on the blood glucose response to a nutrient drink and energy intake, in lean and obese men. Nutrients 2018;10(4). pii: PubMed

See these in context on the L-tryptophan monograph →

Melatonin 118 references
  1. Voordouw BC, Euser R, Verdonk RE, et al. Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab 1992;74:108-17. DOI
  2. Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996;5:61-5. PubMed
  3. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatr 1993;33:526-30. PubMed
  4. Claustrat B, Brun J, David M, et al. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatr 1992;32:705-11.
  5. Fauteck J, Schmidt H, Lerchl A, et al. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 1999;8:105-10. PubMed
  6. Arangino S, Cagnacci A, Angiolucci M, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol 1999;83:1417-9. PubMed
  7. Pierce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: The Stonesong Press, 1999:19.
  8. Lancioni GE, O'Reilly MF, Basili G. Review of strategies for treating sleep problems in persons with severe or profound mental retardation or multiple handicaps. Am J Ment Retard 1999;104:170-86. PubMed
  9. Carman JS, Post RM, Buswell R, et al. Negative effects of melatonin on depression. Am J Psychiatry 1976;133:1181-1186. PubMed
  10. Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
  11. Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp., 1999.
  12. Lusardi P, et al. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol 2000;49:423-7. PubMed
  13. von Bahr C, Ursing C, Yasui N, et al. Fluvoxamine but not citalopram increases serum melatonin in healthy subjects – an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin. Eur J Clin Pharmacol 2000;56:123-7.
  14. Grozinger M, Hartter S, Wang X, et al. Fluvoxamine strongly inhibits melatonin metabolism in a patient with low-amplitude melatonin profile. Arch Gen Psychiatry 2000 Aug;57:812-3. PubMed
  15. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solic tumor patients with poor clinical status. Eur J Cancer 1999;35:1688-92.
  16. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254. PubMed
  17. Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
  18. Wright KP Jr, Myers BL, Plenzler SC, et al. Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives. Brain Res 2000;873:310-7.
  19. Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev 2001;(1):CD001520.
  20. Briggs, Freeman, Yafee. Update Drugs in Pregnancy and Lactation. Lippincott Williams & Wilkins, 2001.
  21. Suhner A, Schlagenhauf P, Johnson R, et al. Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int 1998;15:655-66. PubMed
  22. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520. PubMed
  23. Munoz-Hoyos A, Sanchez-Forte M, Molina-Carballo A, et al. Melatonin's role as an anticonvulsant and neuronal protector: experimental and clinical evidence. J Child Neurol 1998;13:501-9.. PubMed
  24. Sandyk R, Tsagas N, Anninos PA. Melatonin as a proconvulsive hormone in humans. Int J Neurosci 1992;63:125-35.. PubMed
  25. Golombek DA, Escolar E, Burin LJ, et al. Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism. Chronobiol Int 1992;9:124-31.. PubMed
  26. Smits MG, Nagtegaal EE, van der Heijden J, et al. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol 2001;16:86-92.. PubMed
  27. Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf) 2001;54:339-46.. PubMed
  28. Williamson BL, Tomlinson AJ, Naylor S, Gleich GJ. Contaminants in commercial preparations of melatonin. Mayo Clin Proc 1997;72:1094-5. PubMed
  29. Williamson BL, Tomlinson AJ, Mishra PK, et al. Structural characterization of contaminants found in commercial preparations of melatonin: similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. Chem Res To
  30. Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85.. PubMed
  31. Molina-Carballo A, Munoz-Hoyos A, Reiter RJ, et al. Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: two years' experience. J Pineal Res 1997;23:97-105.. PubMed
  32. Tjon Pian Gi CV, Broeren JP, Starreveld JS, A Versteegh FG. Melatonin for treatment of sleeping disorders in children with attention deficit/hyperactivity disorder: a preliminary open label study. Eur J Pediatr 2003;162:554-5. PubMed
  33. Secreto G, Chiechi LM, Amadori A, et al. Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. Maturitas 2004;47:11-20. PubMed
  34. Weiss MD, Wasdell MB, Bomben MM, et al. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry 2006;45:512-9. DOI
  35. Saha L, Malhotra S, Rana S, et al. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol 2007;41:29-32. PubMed
  36. Hussain, SA, Khadim, HM, Khalaf, BH, et al. Effects of melatonin and zinc on glycemic control in type 2 diabetic patients poorly controlled with metformin. Saudi Med J 2006;27:1483-8. DOI
  37. Kadhim, HM, Ismail, SH, Hussein, KI, et al. Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. J Pineal Res 2006;41:189-93. PubMed
  38. Mutluay R. Elbeg S. Karakus R. et al. The Impact of Melatonin on Glucose Homeostasis. Turkish Journal of Endocrinology and Metabolism 2009;13:52-55.
  39. Wright KP Jr, Badia P, Myers BL, et al. Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans. Brain Res. 1997;747(1):78-84. PubMed
  40. Peuhkuri K, Sihvola N, Korpela R. Dietary factors and fluctuating levels of melatonin. Food Nutr Res. 2012;56. doi: 10.3402/fnr.v56i0.17252. Epub 2012 Jul 20. PubMed
  41. Gibb JW, Bush L, Hanson GR. Exacerbation of methamphetamine-induced neurochemical deficits by melatonin. J Pharmacol Exp Ther. 1997;283(2):630-5. DOI
  42. Sunami E, Usuda K, Nishiyama Y, et al. A preliminary study of fluvoxamine maleate on depressive state and serum melatonin levels in patients after cerebral infarction. Intern Med. 2012;51(10):1187-93. PubMed
  43. Babkoff, H., French, J., Whitmore, J., and Sutherlin, R. Single-dose bright light and/or caffeine effect on nocturnal performance. Aviat.Space Environ.Med. 2002;73(4):341-350.
  44. Rossignol, D. A. Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann.Clin Psychiatry 2009;21(4):213-236. DOI
  45. Yeleswaram, K., Vachharajani, N., and Santone, K. Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 1999;26(3):190-191. PubMed
  46. Jan, J. E., Connolly, M. B., Hamilton, D., Freeman, R. D., and Laudon, M. Melatonin treatment of non-epileptic myoclonus in children. Dev.Med Child Neurol. 1999;41(4):255-259. PubMed
  47. Edwards, B. J., Atkinson, G., Waterhouse, J., Reilly, T., Godfrey, R., and Budgett, R. Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones. Ergonomics 2000;43(10):1501-1513. PubMed
  48. Cagnacci, A., Arangino, S., Angiolucci, M., Melis, G. B., Facchinetti, F., Malmusi, S., and Volpe, A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf PubMed
  49. Wakatsuki, A., Okatani, Y., Ikenoue, N., Kaneda, C., and Fukaya, T. Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women. Maturitas 4-20-2001;38(2):171-177. PubMed
  50. Kitajima, T., Kanbayashi, T., Saitoh, Y., Ogawa, Y., Sugiyama, T., Kaneko, Y., Sasaki, Y., Aizawa, R., and Shimisu, T. The effects of oral melatonin on the autonomic function in healthy subjects. Psychiatry Clin Neurosci. 2001;55(3):299-300. PubMed
  51. Calvo, J. R., Guerrero, J. M., Osuna, C., Molinero, P., and Carrillo-Vico, A. Melatonin triggers Crohn's disease symptoms. J Pineal Res 2002;32(4):277-278. PubMed
  52. Luboshitzky, R., Shen-Orr, Z., Nave, R., Lavi, S., and Lavie, P. Melatonin administration alters semen quality in healthy men. J Androl 2002;23(4):572-578. DOI
  53. Rufo-Campos, M. [Melatonin and epilepsy]. Rev Neurol. 2002;35 Suppl 1:S51-S58.
  54. Ursing, C., Wikner, J., Brismar, K., and Rojdmark, S. Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450(CYP)1A2. J.Endocrinol.Invest 2003;26(5):403-406. PubMed
  55. Smits, M. G., van Stel, H. F., van der, Heijden K., Meijer, A. M., Coenen, A. M., and Kerkhof, G. A. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad.Chi PubMed
  56. Boeve, B. F., Silber, M. H., and Ferman, T. J. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281-284. PubMed
  57. Hartter, S., Nordmark, A., Rose, D. M., Bertilsson, L., Tybring, G., and Laine, K. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br.J.Clin.Pharmacol. 2003;56(6):679-682. PubMed
  58. Scheer, F. A., Van Montfrans, G. A., van Someren, E. J., Mairuhu, G., and Buijs, R. M. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43(2):192-197. PubMed
  59. Buscemi, N., Vandermeer, B., Pandya, R., Hooton, N., Tjosvold, L., Hartling, L., Baker, G., Vohra, S., and Klassen, T. Melatonin for treatment of sleep disorders. Evid.Rep.Technol.Assess.(Summ.) 2004;(108):1-7.
  60. Cavallo, A., Ris, M. D., Succop, P., and Jaskiewicz, J. Melatonin treatment of pediatric residents for adaptation to night shift work. Ambul.Pediatr. 2005;5(3):172-177. PubMed
  61. Faber, M. S., Jetter, A., and Fuhr, U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97(3):125-134. PubMed
  62. Cagnacci, A., Cannoletta, M., Renzi, A., Baldassari, F., Arangino, S., and Volpe, A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005;18(12 Pt 1):1614-1618. PubMed
  63. Weekley, L. B. Melatonin-induced relaxation of rat aorta: interaction with adrenergic agonists. J Pineal Res 1991;11(1):28-34. PubMed
  64. Grossman, E., Laudon, M., Yalcin, R., Zengil, H., Peleg, E., Sharabi, Y., Kamari, Y., Shen-Orr, Z., and Zisapel, N. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med 2006;119(10):898-902. PubMed
  65. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241. PubMed
  66. Klupinska, G., Poplawski, T., Drzewoski, J., Harasiuk, A., Reiter, R. J., Blasiak, J., and Chojnacki, J. Therapeutic effect of melatonin in patients with functional dyspepsia. J.Clin.Gastroenterol. 2007;41(3):270-274. PubMed
  67. Bjorvatn, B., Stangenes, K., Oyane, N., Forberg, K., Lowden, A., Holsten, F., and Akerstedt, T. Randomized placebo-controlled field study of the effects of bright light and melatonin in adaptation to night work. Scand.J Work Environ.Health 2007;33(3):204 PubMed
  68. Wirtz, P. H., Spillmann, M., Bartschi, C., Ehlert, U., and von Kanel, R. Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. J Pineal Res 2008;44(2):127-133. PubMed
  69. Bendz, L. M. and Scates, A. C. Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann.Pharmacother. 2010;44(1):185-191. PubMed
  70. Elkhayat, H. A., Hassanein, S. M., Tomoum, H. Y., Abd-Elhamid, I. A., Asaad, T., and Elwakkad, A. S. Melatonin and sleep-related problems in children with intractable epilepsy. Pediatr.Neurol. 2010;42(4):249-254. PubMed
  71. van Geijlswijk, I. M., van der Heijden, K. B., Egberts, A. C., Korzilius, H. P., and Smits, M. G. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT. Psychopharmacology (Berl) 2010;212(3):379-391. PubMed
  72. Wade AG, Ford I, Crawford G, et al. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med 2010;8:51. PubMed
  73. Al-Aama, T., Brymer, C., Gutmanis, I., Woolmore-Goodwin, S. M., Esbaugh, J., and Dasgupta, M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int.J.Geriatr.Psychiatry 2011;26(7):687-694. PubMed
  74. Alstadhaug, K. B., Odeh, F., Salvesen, R., and Bekkelund, S. I. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology 10-26-2010;75(17):1527-1532. PubMed
  75. Wade, A. G., Crawford, G., Ford, I., McConnachie, A., Nir, T., Laudon, M., and Zisapel, N. Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response. Curr.Med.Res.Opin. 2011;27(1):87 PubMed
  76. van Geijlswijk, I. M., Korzilius, H. P., and Smits, M. G. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep 2010;33(12):1605-1614. PubMed
  77. Guenole, F., Godbout, R., Nicolas, A., Franco, P., Claustrat, B., and Baleyte, J. M. Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion. Sleep Med.Rev. 2011;15(6):379-387. PubMed
  78. Rossignol, D. A. and Frye, R. E. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev.Med.Child Neurol. 2011;53(9):783-792. PubMed
  79. Eryilmaz, O. G., Devran, A., Sarikaya, E., Aksakal, F. N., Mollamahmutoglu, L., and Cicek, N. Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems. J.Assist.Reprod.Genet. 2011;28 PubMed
  80. Batioglu, A. S., Sahin, U., Gurlek, B., Ozturk, N., and Unsal, E. The efficacy of melatonin administration on oocyte quality. Gynecol.Endocrinol. 2012;28(2):91-93.
  81. Grossman, E., Laudon, M., and Zisapel, N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc.Health Risk Manag. 2011;7:577-584. PubMed
  82. Nickelsen, T., Demisch, L., Demisch, K., Radermacher, B., and Schoffling, K. Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial. J Pineal Res 1989;6(4):325-334. PubMed
  83. Wright, J., Aldhous, M., Franey, C., English, J., and Arendt, J. The effects of exogenous melatonin on endocrine function in man. Clin Endocrinol (Oxf) 1986;24(4):375-382. PubMed
  84. Papavasiliou, P. S., Cotzias, G. C., Duby, S. E., Steck, A. J., Bell, M., and Lawrence, W. H. Melatonin and parkinsonism. JAMA 7-3-1972;221(1):88-89. DOI
  85. Middleton, B. A., Stone, B. M., and Arendt, J. Melatonin and fragmented sleep patterns. Lancet 8-24-1996;348(9026):551-552. PubMed
  86. Holliman, B. J. and Chyka, P. A. Problems in assessment of acute melatonin overdose. South.Med J 1997;90(4):451-453. PubMed
  87. Hong, Y. G. and Riegler, J. L. Is melatonin associated with the development of autoimmune hepatitis? J Clin Gastroenterol 1997;25(1):376-378. PubMed
  88. Cagnacci, A., Arangino, S., Angiolucci, M., Maschio, E., and Melis, G. B. Influences of melatonin administration on the circulation of women. Am J Physiol 1998;274(2 Pt 2):R335-R338. PubMed
  89. U.S.Food and Drug Administration. Special Nutritionals Adverse Events Monitoring System: registered case reports.
  90. Brueske V, Allen J, Kepic T, and et al. Melatonin inhibition of seizure activity in man [abstract]. Electroencephalog Clin Neurophysiol 1981;51:20P.
  91. Siddiqui MA, Nazmi AS, Karim S, and et al. Effect of melatonin and valproate in epilepsy and depression. Indian J Pharmacol 2001;33:378-381.
  92. Appleton RE, Jones AP, Gamble C, et al. The use of MElatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS). Health Technol Assess. 2012;16(40):i-239. PubMed
  93. Bardazzi F, Placucci F, Neri I, D&apos;Antuono A, Patrizi A. Fixed drug eruption due to melatonin. Acta Derm Venereol. 1998 Jan;78(1):69-70. PubMed
  94. Eckerberg B, Lowden A, Nagai R, Akerstedt T. Melatonin treatment effects on adolescent students&apos; sleep timing and sleepiness in a placebo-controlled crossover study. Chronobiol Int. 2012;29(9):1239-48.
  95. Khezri MB, Merate H. The effects of melatonin on anxiety and pain scores of patients, intraocular pressure, and operating conditions during cataract surgery under topical anesthesia. Indian J Ophthalmol. 2013;61(7):319-24. PubMed
  96. Khezri MB, Oladi MR, Atlasbaf A. Effect of melatonin and gabapentin on anxiety and pain associated with retrobulbar eye block for cataract surgery: a randomized double-blind study. Indian J Pharmacol. 2013;45(6):581-6. PubMed
  97. Nishihara T, Hashimoto S, Ito K, et al. Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2014;30(5):359-62.
  98. De Bleecker JL, Lamont BH, Verstraete AG, Schelfhout VJ. Melatonin and painful gynecomastia. Neurology. 1999 Jul 22;53(2):435-6. PubMed
  99. Waldron DL, Bramble D, Gringras P. Melatonin: prescribing practices and adverse events. Arch Dis Child. 2005 Nov;90(11):1206-7. PubMed
  100. Chojnacki C, Walecka-Kapica E, Lokiec K, et al. Influence of melatonin on symptoms of irritable bowel syndrome in postmenopausal women. Endokrynol Pol. 2013;64(2):114-20.
  101. Kim MK, Park EA, Kim HJ, et al. Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS? Reprod Biomed Online. 2013;26(1):22-9. PubMed
  102. Silman RE. Melatonin: a contraceptive for the nineties. Eur J Obstet Gynecol Reprod Biol. 1993;49(1-2):3-9. PubMed
  103. Briggs GG, Freeman RK, Forinash AB, Towers CV. Drugs in Pregnancy and Lactation. 11th ed. Philadelphia, PA: Wolters Kluwer, 2017.
  104. Onseng K, Johns NP, Khuayjarernpanishk T, et al. Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation. J Altern Complement Med 2017;23(12):957-63. PubMed
  105. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. PubMed
  106. Gonçalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016;87(10):1127-32. PubMed
  107. Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL. Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry 2017;56(11):948-57.e4. PubMed
  108. Baandrup L, Lindschou J, Winkel P, Gluud C, Glenthoj BY. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder: A randomised, placebo-controlled, blinded trial. World J Biol Psychi PubMed
  109. Lui MFG, Chow HKD, Wong WMK, Tsang WNW. Melatonin affects postural control in community-dwelling older adults while dual-tasking: a randomized observation study. J Aging Phys Act. 2018 May 29:1-24. PubMed
  110. Fallah R, Shoroki FF, Ferdosian F. Safety and efficacy of melatonin in pediatric migraine prophylaxis. Curr Drug Saf. 2015;10(2):132-5. PubMed
  111. Scheuer C, Pommergaard HC, Rosenberg J, Gogenur I. Effect of topical application of melatonin cream 12.5% on cognitive parameters: a randomized, placebo-controlled, double-blind crossover study in healthy volunteers. J Dermatolog Treat. 2016 Nov;27(6):488 PubMed
  112. Doosti-Irani A, Ostadmohammadi V, Mirhosseini N et al. The effects of melatonin supplementation on glycemic control: A systematic review and meta-analysis of randomized controlled trials. Horm Metab Res. 2018;50(11):783-790. PubMed
  113. Farrokhian A, Tohidi M, Ahanchi NS, et al. Effect of bedtime melatonin administration in patients with type 2 diabetes: A triple-blind, placebo-controlled, randomized trial. Iran J Pharm Res. 2019;18(Suppl1):258-268.
  114. Hayashi M, Mishima K, Fukumizu M, et al. Melatonin treatment and adequate sleep hygiene interventions in children with autism spectrum disorder: A randomized controlled trial. J Autism Dev Disord 2021. PubMed
  115. Esmaeili A, Nassiri Toosi M, Taher M, et al. A pilot randomized, clinical trial of the anti-pruritus effect of melatonin in patients with chronic liver disease. Iran J Pharm Res 2021;20(2):462-472.
  116. Yan W, Li C, Song X, Zhou W, Chen Z. Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis. Medicine (Baltimore) 2022;101(43):e31411. PubMed
  117. Ameri A, Frouz Asadi M, Ziaei A, et al. Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial. Inflammopharmacology 2023;31(1):265-274. PubMed
  118. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949. PubMed

See these in context on the Melatonin monograph →

Theanine 6 references
  1. Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-glutamylethylamide in spontaneously hypertensive rats. Life Sci 1998;62:1065-8.
  2. Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., and Scholey, A. B. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol.Psychol. 2008;77(2):113-122. PubMed
  3. Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T., and Takeuchi, N. Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci.Biotechnol.Biochem. 1995;59(4):615-618. PubMed
  4. Lyon MR, Kapoor MP, Juneja LR. The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern Med Rev. 2011;16(4):348-
  5. Hidese S, Ota M, Wakabayashi C, et al. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr 2017;29(2):72-9.
  6. Tsuchiya T, Honda H, Oikawa M, et al. Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients. Int J Clin Oncol 2016;21(6):1085-90. PubMed

See these in context on the Theanine monograph →

L-carnitine 41 references
  1. Ellaway CM, Williams K, Leonard H, et al. Rett syndrome: randomized controlled trial of L-carnitine. J Child Neurol 1999;14:162-7. PubMed
  2. Anon. Carnitor (levocarnitine) package insert. Sigma-Tau Pharmaceuticals Inc, Gaithersburg, MD. December 1999.
  3. Cherchi A, Lai C, Angelino F, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo-controlled, crossover study. Int J Clin Pharmacol Ther Toxicol 1985;23:569-72.
  4. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology 1997;35:16-23. PubMed
  5. Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Meta
  6. Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.
  7. Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385. PubMed
  8. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet 2003;42:941-67. PubMed
  9. 12761 Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 2004;1033:158-67. PubMed
  10. Ciacci C, Peluso G, Iannoni E, et al. L-Carnitine in the treatment of fatigue in adult celiac disease patients: a pilot study. Dig Liver Dis 2007;39:922-8. PubMed
  11. Cruciani RA, Dvorkin E, Homel P, et al. Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. J Pain Symptom Manage 2006;32:551-9. PubMed
  12. Lebrun C, Alchaar H, Candito M, et al. Levocarnitine administration in multiple sclerosis patients with immunosuppressive therapy-induced fatigue. Mult Scler 2006;12:321-4. PubMed
  13. Malaguarnera M, Cammalleri L, Gargante MP, et al. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 2007;86:1738-44. PubMed
  14. Mantovani G, Maccio A, Madeddu C, et al. Randomized phase III clinical trial of five different arms of treatment in 322 patients with cancer cachexia. Oncologist 2010;15:200-11.
  15. Angelova-Fischer I, Rippke F, Fischer TW, Neufang G, Zillikens D. A double-blind, randomized, vehicle-controlled efficacy assessment study of a skin care formulation for improvement of mild to moderately severe acne. J Eur Acad Dermatol Venereol. 2013 Jul PubMed
  16. Hatamkhani S, Khalili H, Karimzadeh I, Dashti-Khavidaki S, Abdollahi A, Jafari S. Carnitine for prevention of antituberculosis drug-induced hepatotoxicity: a randomized, clinical trial. J Gastroenterol. Hepatol. 2014 May;29(5):997-1004. PubMed
  17. Boehm G, Stahl B. Oligosaccharides from milk. J Nutr 2007;137(3 Suppl 2):847S-849S.
  18. Van Oudheusden, L. J. and Scholte, H. R. Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Prostaglandins Leukot.Essent.Fatty Acids 2002;67(1):33-38. PubMed
  19. Derosa, G., Cicero, A. F., Gaddi, A., Mugellini, A., Ciccarelli, L., and Fogari, R. The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus. Clin Ther 2003;25(5):1429-1439. PubMed
  20. Foitzik, K., Hoting, E., Heinrich, U., Tronnier, H., and Paus, R. Indications that topical L-carnitin-L-tartrate promotes human hair growth in vivo. J Dermatol.Sci 2007;48(2):141-144. PubMed
  21. Kumar, A., Singh, R. B., Saxena, M., Niaz, M. A., Josh, S. R., Chattopadhyay, P., Mechirova, V., Pella, D., and Fedacko, J. Effect of carni Q-gel (ubiquinol and carnitine) on cytokines in patients with heart failure in the Tishcon study. Acta Cardiol. 20
  22. Cruciani, R. A., Dvorkin, E., Homel, P., Culliney, B., Malamud, S., Lapin, J., Portenoy, R. K., and Esteban-Cruciani, N. L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. J Pa PubMed
  23. Malaguarnera, M., Vacante, M., Avitabile, T., Malaguarnera, M., Cammalleri, L., and Motta, M. L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Am J Clin.Nutr 2009;89(1):71-76. PubMed
  24. Alvarez, T. M., Guardiola, P. D., Roldan, J. O., Elviro, R., Wevers, R., and Guijarro, G. [Primary trimethylaminuria: the fish odor syndrome]. Endocrinol.Nutr. 2009;56(6):337-340.
  25. Wu, Z. M., Lu, X., Wang, Y. W., Sun, J., Tao, J. W., Yin, F. H., and Cheng, H. J. [Short-term medication of L-carnitine before intracytoplasmic sperm injection for infertile men with oligoasthenozoospermia]. Zhonghua Nan.Ke.Xue 2012;18(3):253-256.
  26. Tarighat, Esfanjani A., Mahdavi, R., Ebrahimi, Mameghani M., Talebi, M., Nikniaz, Z., and Safaiyan, A. The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis. Biol.Trace Elem.Res 2012;150(1-3): PubMed
  27. DiNicolantonio, J. J., Lavie, C. J., Fares, H., Menezes, A. R., and O'Keefe, J. H. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544-551. PubMed
  28. Huang, W. W., Wang, M. Y., Shi, H. M., Peng, Y., Peng, C. S., Zhang, M., Li, Y., Lu, J., and Li, X. B. Comparative study of bioactive constituents in crude and processed Glycyrrhizae radix and their respective metabolic profiles in gastrointestinal tract
  29. Madsen KL, Preisler N, Orngreen MC, Andersen SP, Olesen JH, Lund AM, Vissing J. Patients with medium-chain acyl-coenzyme a dehydrogenase deficiency have impaired oxidation of fat during exercise but no effect of L-carnitine supplementation. J Clin Endocri
  30. Prohaska ES, Muzyk AJ, Rivelli SK. Levocarnitine-induced hypophosphatemia in a hemodialysis patient with acute valproic acid toxicity. J Neuropsychiatry Clin Neurosci. 2012 Winter;24(1):E18-9. PubMed
  31. Shang R, Sun Z, Li H. Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2014 Jul 21;14:88. PubMed
  32. Zhang JJ, Wu ZB, Cai YJ, Ke B, Huang YJ, Qiu CP, Yang YB, Shi LY, Qin J. L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study. Nutr J. 2014 Nov 26;13:110. PubMed
  33. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L-carn
  34. Jun DW, Kim BI, Cho YK, Kim HJ, Kwon YO, Park SY, Han SY, Baek YH, Jung YJ, Kim HY, Kim W, Heo J, Woo HY, Hwang SG, Rim KS, Choi JY, Bae SH, Lee YS, Lim YS,Cheong JY, Cho SW, Lee BS, Kim SH, Sohn JH, Kim TY, Paik YH, Kim JK, Lee KS. Efficacy and safety of
  35. An JH, Kim YJ, Kim KJ, et al. L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial. Endocr J. 2016;63(10):885-95. PubMed
  36. Chen N, Yang M, Zhou M, Xiao J, Guo J, He L. L-carnitine for cognitive enhancement in people without cognitive impairment. Cochrane Database Syst Rev. 2017;3:CD009374. PubMed
  37. Khajeh B, Dashti-Khavidaki S, Nasiri-Toosi M, Mohammadi K, Jafari A. Effects of pre-transplant L-carnitine supplementation on primary graft dysfunction in liver transplant recipients: a pilot, randomized, placebo-controlled clinical trial. Res Pharm Sci. PubMed
  38. Kubota K, Uojima H, Shao X, et al. Additional L-carnitine Reduced the Risk of Hospitalization in Patients with Overt Hepatic Encephalopathy on Rifaximin. Dig Dis 2021. PubMed
  39. Amini L, Yaghini O, Ghazavi M, Aslani N. L-carnitine versus propranolol for pediatric migraine prophylaxis. Iran J Child Neurol 2021;15(2):77-86.
  40. Shakibaei F, Jelvani D. Effect of adding l -carnitine to risperidone on behavioral, cognitive, social, and physical symptoms in children and adolescents with autism: A randomized double-blinded placebo-controlled clinical trial. Clin Neuropharmacol 2023;4 PubMed
  41. Moustafa I, Connolly C, Anis M, Mustafa H, Oosthuizen F, Viljoen M. A prospective study to evaluate the efficacy and safety of vitamin E and levocarnitine prophylaxis against doxorubicin-induced cardiotoxicity in adult breast cancer patients. J Oncol Phar PubMed

See these in context on the L-carnitine 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 →

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

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Lemon Balm 12 references
  1. Wolbling RH, Leonhardt K. Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine 1994;1:25-31.
  2. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry 2003;74:863-6. PubMed
  3. Kennedy DO, Scholey AB, Tildesley NT, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav 2002;72:953-64. PubMed
  4. Albrecht M, Berger W, Laux P, Schmidt U, et al. Psychopharmaka und Verkehrssicherheit. Der Einfluß von Euvegal&reg; - Dragees forte auf die Fahrtüchtigkeit und Kombinationswirkungen mit Alkohol Z Allg Med 1995;71:1215-25.
  5. Herberg, KW. Nebenwirkungen pflanzlicher Beruhigungsmittel/ Leistung und Befinden nach Einnahme einer Baldrian-Hopfen-Kombination. Z.Allg Med 1996;72:234-240.
  6. Soulimani R, Fleurentin J, Mortier F, et al. Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse. Planta Med. 1991 Apr;57:105-9.
  7. Sourgens H, Winterhoff H, Gumbinger HG, et al. Antihormonal effects of plant extracts. TSH- and prolactin-suppressing properties of Lithospermum officinale and other plants. Planta Med. 1982 Jun;45:78-86. DOI
  8. Auf'mkolk M, Ingbar JC, Amir SM, et al. Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. Endocrinology. 1984 Aug;115:527-34. PubMed
  9. Santini F, Vitti P, Ceccarini G, et al. In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest. 2003 Oct;26:950-5. PubMed
  10. Alijaniha F, et al. Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. J Ethnopharmacol. 2015;164:378-384. doi: 10.1016/j.jep.2015.02.007. Epub 2015 Feb 11. PubMed
  11. Araj-Khodaei M, Noorbala AA, Yarani R, et al. A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression. BMC Complement Med Ther. 2020;20(1):207. PubMed
  12. Kucuk U, Pham M, Raza Raja MH, Saad Shaukat MH, Clark R. Transient complete atrioventricular block associated with herbal supplement use. S D Med 2023;76(7):311-313.

See these in context on the Lemon Balm monograph →

Valerian 37 references
  1. Willey LB, Mady SP, Cobaugh DJ, Wax PM. Valerian overdose: a case report. Vet Hum Toxicol 1995;37:364-5.
  2. Kuhlmann J, Berger W, Podzuweit H, Schmidt U. The influence of valerian treatment on "reaction time, alertness and concentration" in volunteers. Pharmacopsychiatry 1999;32:235-41. PubMed
  3. Klepser TB, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health Syst Pharm 1999;56:125-38. PubMed
  4. Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 1999;51:505-12. PubMed
  5. Garges HP, Varia I, Doraiswamy PM. Cardiac complications and delirium associated with Valerian root withdrawal. [Letter to the Editor]. JAMA 1998;280:1566-7. PubMed
  6. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  7. MacGregor FB, Abernethy VE, Dahabra S, et al. Hepatotoxicity of herbal remedies. BMJ 1989;299:1156-7. PubMed
  8. Leathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med 1985;2:144-8. PubMed
  9. Hadley S, Petry JJ. Valerian. Am Fam Physician 2003;67:1755-8..
  10. Glass JR, Sproule BA, Herrmann N, et al. Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J Clin Psychopharmacol 2003;23:260-8. PubMed
  11. Lefebvre T, Foster BC, Drouin CE, et al. In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4. J Pharm Pharmaceut Sci 2004;7:265-73.
  12. Yuan CS, Mehendale S, Xiao Y, et al. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 2004;98:353-8. PubMed
  13. Donovan JL, DeVane CL, Chavin KD, et al. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:1333-6. PubMed
  14. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  15. Gutierrez S, Ang-Lee MK, Walker DJ, Zacny JP. Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers. Pharmacol Biochem Behav 2004;78:57-64. PubMed
  16. Jacobs BP, Bent S, Tice JA, et al. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine (Baltimore) 2005;84:197-207. PubMed
  17. National Toxicology Program, US Department of Health and Human Services. Chemical Information Review Document for Valerian (Valeriana officinalis L.) [CAS No. 8057-49-6] and Oils [CAS No. 8008-88-6]. Supporting Nomination for Toxicological Evaluation by t
  18. Fernández-San-Martín MI, Masa-Font R, Palacios-Soler L, et al. Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. 2010 Jun;11:505-11. PubMed
  19. Coxeter PD, Schluter PJ, Eastwood HL, et al. Valerian does not appear to reduce symptoms for patients with chronic insomnia in general practice using a series of randomised n-of-1 trials. Complement Ther Med. 2003 Dec;11:215-22. PubMed
  20. Diaper A, Hindmarch I. A double-blind, placebo-controlled investigation of the effects of two doses of a valerian preparation on the sleep, cognitive and psychomotor function of sleep-disturbed older adults. Phytother Res. 2004 Oct;18:831-6. PubMed
  21. Cuellar NG, Ratcliffe SJ. Does valerian improve sleepiness and symptom severity in people with restless legs syndrome? Altern Ther Health Med 2009;15:22-8.
  22. Chen D, Klesmer J, Giovanniello A, et al. Mental status changes in an alcohol abuser taking valerian and gingko biloba. Am J Addict. 2002 Winter;11:75-7. PubMed
  23. Albrecht M, Berger W, Laux P, Schmidt U, et al. Psychopharmaka und Verkehrssicherheit. Der Einfluß von Euvegal&reg; - Dragees forte auf die Fahrtüchtigkeit und Kombinationswirkungen mit Alkohol Z Allg Med 1995;71:1215-25.
  24. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009 Dec;23:1795-6.
  25. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. 2007 Nov;101:350-8.
  26. Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol. 2007 Jan;100:23-30. PubMed
  27. Alkharfy, K. M. and Frye, R. F. Effect of valerian, valerian/hops extracts, and valerenic acid on glucuronidation in vitro. Xenobiotica 2007;37(2):113-123.
  28. Vassiliadis, T., Anagnostis, P., Patsiaoura, K., Giouleme, O., Katsinelos, P., Mpoumponaris, A., and Eugenidis, N. Valeriana hepatotoxicity. Sleep Med 2009;10(8):935. PubMed
  29. Muller, Z., Sarkany, A., Altorjay, A., Szilagyi, A., Tura, T., and Ozsvar, Z. [Liver failure a la Eastern Europe]. Orv.Hetil. 3-22-2009;150(12):555-557. PubMed
  30. National Toxicology Program, US Department of Health and Human Services. Chemical Information Review Document for Valerian (Valeriana officinalis L.) [CAS No. 8057-49-6] and Oils [CAS No. 8008-88-6]. 2009;
  31. Wells SR. International intravenous administration of a crude valerian root extract. NACCT 1995;33:542.
  32. Aydinoglu U, Özcan H, Yücel A, Yücel N, Mutlu M. Valerian induced hypomania: a case report. Bull Clin Psychopharma 2012;22(Suppl. 1):S63.
  33. Mirabi P, Mojab F. The effects of valerian root on hot flashes in menopausal women. Iran J Pharm Res 2013;12(1):217-22.
  34. Thomas K, Canedo J, Perry PJ, et al. Effects of valerian on subjective sedation, field sobriety testing and driving simulator performance. Accid Anal Prev. 2016 Jul;92:240-4. PubMed
  35. Kia YH, Alexander S, Dowling D, Standish R. A case of steroid-responsive valerian-associated hepatitis. Intern Med J. 2016 Jan;46(1):118-9. PubMed
  36. Burke H, Jiang S, Chatham P, Stern TA. Delirium After Withdrawal From Valerian Root: A Case Report. Psychosomatics. 2020;61(6):787-790. PubMed
  37. Hajizadeh I, Jamshidi M, Kazemi M, Kargar H, Sadeghi T. Comparison the effect of valerian and gabapentin on RLS and sleep quality in hemodialysis patients: A randomized clinical trial. Ther Apher Dial 2023.

See these in context on the Valerian monograph →

Griffonia Simplicifolia 22 references
  1. Cangiano C, Ceci F, Cancino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992;56:863-7. PubMed
  2. U.S. Food and Drug Administration. Impurities confirmed in dietary supplement 5-hydroxy-L-tryptophan. FDA Talk Paper, August 31, 1998; T98-48.
  3. Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med 1980;303:782-7. PubMed
  4. Poldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24:53-81.
  5. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache 2000;40:451-6.
  6. U. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. Information Paper on L-Tryptophan and 5-hydroxy-L-tryptophan, February 2001.
  7. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  8. Johnson KL, Klarskov K, Benson LM, et al. Presence of peak X and related compounds: the reported contaminant in case related 5-hydroxy-L-tryptophan associated with eosinophilia-myalgia syndrome. J Rheumatol 1999;26:2714-7.
  9. Iovieno, N., Dalton, E. D., Fava, M., and Mischoulon, D. Second-tier natural antidepressants: review and critique. J Affect.Disord. 2011;130(3):343-357. PubMed
  10. den Boer JA, Westenberg HG. Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. Psychiatry Res 1990;31:267-78. PubMed
  11. Jangid P, Malik P, Singh P, Sharma M, Gulia AK. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr 2013;6:29-34. PubMed
  12. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm 1989;76:109-17. PubMed
  13. Angst J, Woggon B, Schoepf J. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr 1977;224:175-86. DOI
  14. Titus F, Dávalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol 1986;25:327-9. PubMed
  15. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci 1985;29:239-48.
  16. Wyatt, R. J., Vaughan, T., Galanter, M., Kaplan, J., and Green, R. Behavioral changes of chronic schizophrenic patients given L-5- hydroxytryptophan. Science 9-22-1972;177(54):1124-1126. PubMed
  17. van Hiele LJ. l-5-Hydroxytryptophan in depression: the first substitution therapy in psychiatry? The treatment of 99 out-patients with 'therapy-resistant' depressions. Neuropsychobiology 1980;6:230-40. PubMed
  18. Pranzatelli, M. R., Tate, E., Huang, Y., Haas, R. H., Bodensteiner, J., Ashwal, S., and Franz, D. Neuropharmacology of progressive myoclonus epilepsy: response to 5- hydroxy-L-tryptophan. Epilepsia 1995;36(8):783-791. PubMed
  19. Trouillas P, Serratrice G, Laplane D, et al. Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study. Arch Neurol 1995;52:456-60. PubMed
  20. Pardo JV. Mania following addition of hydroxytryptophan to monoamine oxidase inhibitor. Gen Hosp Psychiatry 2012;34(1):102.e13-4. PubMed
  21. Lemaire PA, Adosraku RK. An HPLC method for the direct assay of the serotonin precursor, 5-hydroxytrophan, in seeds of Griffonia simplicifolia. Phytochem Anal 2002;13(6):333-7.
  22. Esposito M, Precenzano F, Sorrentino M, Avolio D, Carotenuto M. A medical food formulation of Griffonia simplicifolia/magnesium for childhood periodic syndrome therapy: an open-label study on motion sickness. J Med Food 2015;18(8):916-20.

See these in context on the Griffonia Simplicifolia monograph →

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

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Hops 15 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217:369-78. PubMed
  4. Milligan SR, Kalita JC, Heyerick A, et al. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab 1999;84:2249-52.. PubMed
  5. Milligan SR, Kalita JC, Pocock V, et al. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab 2000;85:4912-5.. DOI
  6. Henderson MC, Miranda CL, Stevens JF, et al. In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus. Xenobiotica 2000;30:235-51.. PubMed
  7. Mannering, G. J., Shoeman, J. A., and Deloria, L. B. Identification of the antibiotic hops component, colupulone, as an inducer of hepatic cytochrome P-4503A in the mouse. Drug Metab Dispos 1992;20(2):142-147. DOI
  8. Skorska, C., Mackiewicz, B., Gora, A., Golec, M., and Dutkiewicz, J. Health effects of inhalation exposure to organic dust in hops farmers. Ann.Univ Mariae.Curie Sklodowska [Med] 2003;58(1):459-465.
  9. Schiller, H., Forster, A., Vonhoff, C., Hegger, M., Biller, A., and Winterhoff, H. Sedating effects of Humulus lupulus L. extracts. Phytomedicine. 2006;13(8):535-541. PubMed
  10. van Hunsel, F. P. and Kampschoer, P. [Postmenopausal bleeding and dietary supplements: a possible causal relationship with hop- and soy-containing preparations]. Ned.Tijdschr.Geneeskd. 2012;156(41):A5095.
  11. Fenselau, C. and Talalay, P. Is oestrogenic activity present in hops? Food Cosmet.Toxicol. 1973;11(4):597-602. PubMed
  12. Godnic-Cvar, J., Zuskin, E., Mustajbegovic, J., Schachter, E. N., Kanceljak, B., Macan, J., Ilic, Z., and Ebling, Z. Respiratory and immunological findings in brewery workers. Am J Ind Med 1999;35(1):68-75. DOI
  13. Lee KM, Jung JS, Song DK, and et al. Effects of Humulus lupulus extract on the central nervous system in mice. Planta Med 1993;59(Suppl):A691.
  14. Assessment report on Humulus lupulus L., flos. European Medicines Agency, 2014. Available at: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-humulus-lupulus-l-flos_en.pdf. Accessed September 29, 2021.
  15. van Breemen RB, Chen L, Tonsing-Carter A, et al. Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women. J Agric Food Chem. 2020;68(18):5212-5220. PubMed

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

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