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Dietary supplement

Clearer Thinking Grapefruit Flavor Ingredients & Drug Interactions

by Instavit

Clearer Thinking Grapefruit Flavor label
See full label image
Liquid 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 Clearer Thinking Grapefruit Flavor 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

Clearer Thinking Grapefruit Flavor is a dietary supplement by Instavit with 11 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,807 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Tea leaf extract, Gingko biloba, Panax ginseng. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Clearer Thinking Grapefruit Flavor by Instavit

Ask about any prescription or over-the-counter medication and we check it for interactions with Clearer Thinking Grapefruit Flavor by Instavit — and tell you which ingredient is responsible.

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Computed from our clinical databases

HelloPharmacist Scorecard of Clearer Thinking Grapefruit Flavor by Instavit

Four independent checks of what is known — a summary of the available information, not a grade of the product itself.

Evidence for Intended Use
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
Not assessable

The stated purpose hasn't been mapped to our evidence data yet.

Why this rating?
  • We haven't mapped this product's purpose to our evidence data yet — it'll be graded on the next content refresh.
Ingredient Transparency
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 11 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (40 mcg) without saying how much of each component you get.
Known Interaction Concern
Major identified

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

Why this rating?
  • 11 of the 11 matched ingredients can interact with medications — Ginkgo, Acetyl-l-carnitine, Vitamin B12, Vitamin B6, Coenzyme Q10, 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; cancer treatments; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,808 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.
Safety Information
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 11 of the 11 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 11 of 11.
  • General safety write-ups exist for 11 of 11.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

HelloPharmacist summaryFormula with limited ingredient disclosure with no assessable stated purpose. Major medication interactions have been identified, and safety information is well characterized.

Assessment coverage: 11 of 11 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 24, 2017.

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 Clearer Thinking Grapefruit Flavor, straight from the product label.

Brand Instavit
Barcode (UPC) 812189020157
Net contents 14 mL; 0.5 fl. Oz.
Market status Off market
Date entered into DSLD Feb 24, 2017
DSLD ID 70802
Product type Other Combinations
Supplement form Liquid
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Clearer Thinking Grapefruit Flavor by Instavit, 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:
0.5 mL
Maximum serving Sizes:
0.5 mL
Servings per container
28
UPC/BARCODE
812189020157
IngredientAmount% DV
Vitamin B62 mg100%
Folic Acid400 mcg100%
Vitamin B126 mcg100%
Vitamin E10 IU33%
Thiamine1.5 mg100%
Proprietary Blend40 mcg--
Acetyl-L-Carnitine0 NP--
Green Tea leaf extract0 NP--
Coenzyme Q100 NP--
Gingko biloba0 NP--
Phosphotidyl Serine0 NP--
Panax ginseng0 NP--

Other ingredients: purified Water, Vegetable Glycerine, Artificial Flavors, Citric Acid, Potassium Sorbate, Sodium Benzoate, Xanthan Gum, modified Gum Acacia, Sucralose, Acesulfame Potassium

Tap any ingredient to jump to its full detail below.

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

Need clearer thinking?

Spray your way with... Clearer Thinking Great tasting Dr formulated No pills to swallow

28 servings

For best before, see side of carton.

Made in the USA

FDA Statement of Identity

Multivitamin Oral Spray Supplement Designed To Support Brain Health

Precautions

Keep out of reach of children.

Do not purchase if seal is broken.

Cautions And Warnings: Do not exceed recommended daily dose.

Instavit Clearer Thinking should not be used as a substitute for a varied and well balanced diet. Do not use if inner seal is broken.

If you are pregnant, nursing, taking any medication or have a medical condition, please consult your healthcare practitioner before taking any dietary supplement.

Not intended for use by children.

Storage

Protect from heat, light and moisture.

Store in a cool dry place below 25(0)C.

Suggested/Recommended/Usage/Directions

Shake prior to use.

1. Open the lid 2. Spray into your mouth 3. Get on with the rest of your day

Recommended Use: Spray 4 sprays into your mouth. Shake before use.

FDA Disclaimer Statement

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

Brand IP Statement(s)

Looking to help support brain health? Instavit Clearer Thinking is a multivitamin nutritional supplement designed to help support brain health and function.

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

See for yourself

Clearer Thinking Grapefruit Flavor by Instavit label

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

Clearer Thinking Grapefruit Flavor 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 Clearer Thinking Grapefruit Flavor by Instavit

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

Serving size0.5 mL Dosage formLiquid Servings per container28 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
2 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

Folic Acid

Interacts with
40 drugs
400 mcg per serving

Folic acid is the man-made form of vitamin B9 and is one of the most well-studied supplements, especially for preventing serious birth defects when ta...

Folic Acid monograph & interactions

Vitamin B12

Interacts with
20 drugs
6 mcg per serving Form: Cyanocobalamin

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

Vitamin B12 monograph & interactions

Vitamin E

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

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

Vitamin E monograph & interactions

Thiamine

Interacts with
3 drugs
1.5 mg per serving Form: Thiamine Hydrochloride

Thiamine (vitamin B1) is an essential nutrient your body needs to turn food into energy and to keep your nerves and heart healthy. Most people get eno...

Thiamine monograph & interactions

Proprietary Blend

40 mcg per serving

Other (inactive) ingredients: Purified Water, Vegetable Glycerine, Artificial Flavors, Citric Acid, Potassium Sorbate, Sodium Benzoate, Xanthan Gum, Modified Gum Acacia, Sucralose, Acesulfame Potassium. These complete the product’s ingredient list but are not active constituents.

Interaction report

Clearer Thinking Grapefruit Flavor by Instavit Drug Interactions

Clearer Thinking Grapefruit Flavor contains 11 ingredients, and 11 of them have known drug interactions. Altogether they interact with 1,807 medications. Here’s the picture, then you can look up your own drug.

Want to check YOUR meds against Clearer Thinking Grapefruit Flavor?

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
1,807Drugs
14 Major 1,790 Moderate 3 Minor

Ingredients driving the most interactions

Green Tea leaf extract 1,293
Gingko biloba 1,266
Panax ginseng 1,130
Vitamin E 764
Phosphotidyl Serine 219

Individual Drug Interactions

The ingredients in Clearer Thinking Grapefruit Flavor interact with 1,807 drugs. Click any drug to see the details.

11 of the 11 ingredients in Clearer Thinking Grapefruit Flavor interact with drugs. Each result below shows which ingredient is responsible. Green Tea leaf extract Gingko biloba Panax ginseng Vitamin E Phosphotidyl Serine Vitamin B6 Acetyl-L-Carnitine Coenzyme Q10 Folic Acid Vitamin B12 Thiamine

Each ingredient & the kinds of drugs it affects

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

Green Tea 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

Gingko biloba23 drug types · 1,266 drugs

Talinolol

Taking ginkgo with talinolol seems to increase blood levels of talinolol.
There is some evidence that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of talinolol by 36% in healthy male individuals. However, single doses of ginkgo do not seem to affect talinolol pharmacokinetics.

Likelihood Probable Evidence B
Alprazolam (Xanax)

Theoretically, ginkgo might decrease the levels and clinical effects of alprazolam.
In clinical research, ginkgo extract (Ginkgold) 120 mg twice daily seems to decrease alprazolam levels by about 17%. However, ginkgo does not appear to decrease the elimination half-life of alprazolam. This suggests that ginkgo is more likely to decrease absorption of alprazolam rather than induce hepatic metabolism of alprazolam.

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin. Theoretically, ginkgo might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. However, population and clinical studies have produced mixed results. Some evidence shows that short-term use of ginkgo leaf does not significantly reduce platelet aggregation and blood clotting. A study in healthy males who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days found no change in prothrombin time. An analysis of a large medical record database suggests that ginkgo increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin. It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation. However, a meta-analysis of 18 studies using standardized ginkgo extracts, 80-480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. In addition, a single dose of ginkgo plus clopidogrel or ticlopidine does not seem to significantly increase bleeding time or platelet aggregation. Also, taking ginkgo leaf extract daily for 8 days in conjunction with rivaroxaban does not affect anti-factor Xa activity; however, this study did not evaluate bleeding time.

Likelihood Possible Evidence A
Anticonvulsants

Theoretically, ginkgo might reduce the effectiveness of anticonvulsants.
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves. Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity. However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking ginkgo with antidiabetes drugs might alter the response to antidiabetes drugs.
Ginkgo leaf extract seems to alter insulin secretion and metabolism, and might affect blood glucose levels in people with type 2 diabetes. The effect of ginkgo seems to differ depending on the insulin and treatment status of the patient. In diet-controlled diabetes patients with hyperinsulinemia, taking ginkgo does not seem to significantly affect insulin or blood glucose levels. In patients with hyperinsulinemia who are treated with oral hypoglycemic agents, taking ginkgo seems to decrease insulin levels and increase blood glucose following an oral glucose tolerance test. Researchers speculate that this could be due to ginkgo-enhanced hepatic metabolism of insulin. In patients with pancreatic exhaustion, taking ginkgo seems to stimulate pancreatic beta-cells, resulting in increased insulin and C-peptide levels, but with no significant change in blood glucose levels in response to an oral glucose tolerance test.

Likelihood Possible Evidence B
Atorvastatin (Lipitor)

Theoretically, ginkgo might decrease the levels and clinical effects of atorvastatin.
In humans, intake of ginkgo extract appears to increase atorvastatin clearance, reducing the area under the curve of atorvastatin by 10% to 14% and the maximum concentration by 29%. However, this interaction does not appear to affect cholesterol synthesis and absorption. Further, a model in rats with hyperlipidemia suggests that administering ginkgo extract does not impact blood levels of atorvastatin and leads to lower total cholesterol, low-density lipoprotein cholesterol, and triglycerides when compared with rats given atorvastatin alone.

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

Theoretically, ginkgo might increase levels of drugs metabolized by CYP1A2.
Laboratory research suggests that ginkgo leaf extract can mildly inhibit CYP1A2 enzymes. However, clinical research suggests ginkgo might not affect CYP1A2. Until more is known, use ginkgo cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.
Some clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce CYP2C19 enzymes and potentially decrease levels of drugs metabolized by these enzymes. However, other clinical research shows that taking ginkgo 120 mg twice daily for 12 days has no effect on levels of drugs metabolized by CYP2C19.

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

Theoretically, ginkgo might increase levels of drugs metabolized by CYP2C9.
In vitro, a specific standardized extract of ginkgo leaf (EGb 761) inhibits CYP2C9 activity . The terpenoid (ginkgolides) and flavonoid (quercetin, kaempferol, etc.) constituents seem to be responsible for this effect. Most ginkgo extracts contain some amount of these constituents. Therefore, other ginkgo leaf extracts might also inhibit the CYP2C9 enzyme. However, clinical research suggests that ginkgo might not have a significant effect on CYP2C9 in humans. Ginkgo does not seem to significantly affect the pharmacokinetics of CYP2C9 substrates diclofenac or tolbutamide.

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

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP3A4.
There is conflicting evidence about whether ginkgo induces or inhibits CYP3A4. Ginkgo does not appear to affect hepatic CYP3A4. However, it is not known if ginkgo affects intestinal CYP3A4. Preliminary clinical research suggests that taking ginkgo does not significantly affect levels of donepezil, lopinavir, or ritonavir, which are all CYP3A4 substrates. Other clinical research also suggests ginkgo does not significantly affect CYP3A4 activity. However, there are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4).

Likelihood Possible Evidence B
Efavirenz (Sustiva)

Theoretically, ginkgo might decrease the levels and clinical effects of efavirenz.
There are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. In one case, an HIV-positive male experienced over a 50% decrease in efavirenz levels over the course of 14 months while taking ginkgo extract. HIV-1 RNA copies also increased substantially, from less than 50 to more than 1500. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4). In another case report, a patient stable on antiviral therapy including efavirenz for 10 years, had an increase in viral load from <50 copies/mL to 1350 copies/mL after 2 months of taking a combination of supplements including ginkgo. After stopping ginkgo, the viral load was again controlled with the same antiviral therapy regimen.

Likelihood Possible Evidence D
Ibuprofen (Advil, Others)

Theoretically, ginkgo might increase the risk of bleeding when used with ibuprofen.
Ginkgo might have antiplatelet effects and has been associated with several case reports of spontaneous bleeding. In one case, a 71-year-old male had taken a specific ginkgo extract (Gingium, Biocur) 40 mg twice daily for 2.5 years. About 4 weeks after starting ibuprofen 600 mg daily he experienced a fatal intracerebral hemorrhage. However, the antiplatelet effects of ginkgo have been questioned. A meta-analysis and other studies have not found a significant antiplatelet effect with standardized ginkgo extracts, 80 mg to 480 mg taken daily for up to 32 weeks.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, taking ginkgo with P-glycoprotein substrates might increase the levels and adverse effects of these substrates.
A small clinical study in healthy volunteers shows that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of the P-glycoprotein substrate, talinolol, by 36% in healthy male individuals. However, single doses of ginkgo do not have the same effect.

Likelihood Possible Evidence B
Risperidone (Risperdal)

Theoretically, taking ginkgo with risperidone might increase the levels and adverse effects of risperidone.
A single case of priapism has been reported for a 26-year-old male with schizophrenia who used risperidone 3 mg daily along with ginkgo extract 160 mg daily. Risperidone is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4. CYP3A4 activity might be affected by ginkgo. Theoretically, ginkgo may inhibit the metabolism of risperidone and increase the risk of adverse effects.

Likelihood Possible Evidence D
Rosiglitazone (Avandia)

Theoretically, ginkgo might decrease the levels and clinical effects of rosiglitazone.
Animal research shows that ginkgo leaf extract orally 100 or 200 mg/kg daily for 10 days alters the pharmacodynamics of rosiglitazone in a dose-dependent manner. The 100 mg/kg and 200 mg/kg doses reduce the area under the concentration time curve (AUC) of rosiglitazone by 39% and 52%, respectively, and the half-life by 28% and 39%, respectively. It is hypothesized that these changes may be due to induction of cytochrome P450 2C8 by ginkgo.

Likelihood Possible Evidence D
Seizure Threshold Lowering Drugs

Theoretically, taking ginkgo with drugs that lower the seizure threshold might increase the risk for convulsions.
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves. Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity. However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy.

Likelihood Possible Evidence D
Simvastatin (Zocor)

Theoretically, ginkgo might decrease the levels and clinical effects of simvastatin.
Clinical research shows that taking ginkgo extract can reduce the area under the curve and maximum concentration of simvastatin by 32% to 39%. However, ginkgo extract does not seem to affect the cholesterol-lowering ability of simvastatin.

Likelihood Probable Evidence B
Sofosbuvir (Sovaldi)

Theoretically, ginkgo might increase the levels and clinical effects of sofosbuvir.
Animal research in rats shows that giving a ginkgo extract 25 mg/kg orally daily for 14 days increases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 11%, increases the half-life by 60%, and increases the plasma concentration at 4 hours by 38%. This interaction appears to be related to the inhibition of intestinal P-glycoprotein by ginkgo.

Likelihood Possible Evidence D
Tacrolimus (Prograf)

Theoretically, ginkgo might increase the blood levels of tacrolimus.
In vitro evidence suggests that certain biflavonoids in ginkgo leaves (i.e. amentoflavone, ginkgetin, bilobetin) may inhibit the metabolism of tacrolimus by up to 50%. This interaction appears to be time-dependent and due to inhibition of cytochrome P450 (CYP) 3A4 by these bioflavonoids. In rats given tacrolimus 1 mg/kg orally, amentoflavone was shown to increase the area under the concentration time curve (AUC) of tacrolimus by 3.8-fold.

Likelihood Possible Evidence D
Trazodone (Desyrel)

Theoretically, ginkgo might increase the levels and clinical effects of trazodone.
In a case report, an Alzheimer patient taking trazodone 20 mg twice daily and ginkgo leaf extract 80 mg twice daily for four doses became comatose. The coma was reversed by administration of flumazenil (Romazicon). Coma might have been induced by excessive GABA-ergic activity. Ginkgo flavonoids are thought to have GABA-ergic activity and act directly on benzodiazepine receptors. Ginkgo might also increase metabolism of trazodone to active GABA-ergic metabolites, possibly by inducing cytochrome P450 3A4 (CYP3A4) metabolism.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. Information from a medical database suggests that when taken concurrently with warfarin, ginkgo increases the risk of a bleeding adverse event by 38%. There is also some evidence that ginkgo leaf extract can inhibit cytochrome P450 2C9, an enzyme that metabolizes warfarin. This could result in increased warfarin levels. However, population and clinical research has produced mixed results. Clinical research in healthy people suggests that ginkgo has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. A meta-analysis of 18 studies using standardized ginkgo extracts, 80 mg to 480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. There is also some preliminary clinical research that suggests ginkgo might not significantly increase the effects of warfarin in patients that have a stable INR.

Likelihood Possible Evidence B
Nifedipine (Procardia)

Theoretically, taking ginkgo with oral, but not intravenous, nifedipine might increase levels and adverse effects of nifedipine.
Animal research and some clinical evidence suggests that taking ginkgo leaf extract orally in combination with oral nifedipine might increase nifedipine levels and cause increased side effects, such as headaches, dizziness, and hot flushes. However, taking ginkgo orally does not seem to affect the pharmacokinetics of intravenous nifedipine.

Likelihood Possible Evidence B
Omeprazole (Prilosec)

Theoretically, taking ginkgo with omeprazole might decrease the levels and clinical effects of omeprazole.
Clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce cytochrome P450 (CYP) 2C19 enzymes and decrease levels of omeprazole by about 27% to 42%.

Likelihood Possible Evidence B
Gingko biloba full monograph & interactions

Panax ginseng20 drug types · 1,130 drugs

Anticoagulant/Antiplatelet Drugs

Although Panax ginseng has shown antiplatelet effects in the laboratory, it is unlikely to increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that ginsenoside constituents in Panax ginseng might decrease platelet aggregation. However, research in humans suggests that ginseng does not affect platelet aggregation. Animal research indicates low oral bioavailability of Rb1 and rapid elimination of Rg1, which might explain the discrepancy between in vitro and human research. Until more is known, use with caution in patients concurrently taking anticoagulant or antiplatelet drugs.

Likelihood Unlikely Evidence B
Antidiabetes Drugs

Theoretically, taking Panax ginseng with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research suggests that Panax ginseng might decrease blood glucose levels. Monitor blood glucose levels closely.

Likelihood Probable Evidence B
Caffeine

Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects. Theoretically, caffeine might have an additive effect on the stimulant effects of Panax ginseng.

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

Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.
There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6%. In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount. However, contradictory research suggests Panax ginseng might not inhibit CYP2D6. Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.
Panax ginseng may affect the clearance of drugs metabolized by CYP3A4. One such drug is imatinib. Inhibition of CYP3A4 was believed to be responsible for a case of imatinib-induced hepatotoxicity. In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4. Clinical research shows that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng. Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.

Likelihood Possible Evidence B
Estrogens

Theoretically, concomitant use of large amounts of Panax ginseng might interfere with hormone replacement therapy.
Laboratory research and some case reports suggest that Panax ginseng can have estrogenic effects due to competition for estrogen receptors. The estrogenic activity is attributed to the ginsenoside constituents of Panax ginseng.

Likelihood Possible Evidence D
Furosemide (Lasix)

Theoretically, Panax ginseng might reduce the effects of furosemide.
There is some concern that Panax ginseng might contribute to furosemide resistance. There is one case of resistance to furosemide diuresis in a patient taking a germanium-containing ginseng product.

Likelihood Possible Evidence D
Imatinib (Gleevec)

Theoretically, Panax ginseng might increase the effects and adverse effects of imatinib.
A case of imatinib-induced hepatotoxicity has been reported for a 26-year-old male with chronic myelogenous leukemia stabilized on imatinib for 7 years. The patient took imatinib 400 mg along with a Panax ginseng-containing energy drink daily for 3 months. Since imatinib-associated hepatotoxicity typically occurs within 2 years of initiating therapy, it is believed that Panax ginseng affected imatinib toxicity though inhibition of cytochrome P450 3A4. CYP3A4 is the primary enzyme involved in imatinib metabolism.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, Panax ginseng use might interfere with immunosuppressive therapy.
Panax ginseng might have immune system stimulating properties.

Likelihood Possible Evidence B
Insulin

Theoretically, taking Panax ginseng with insulin might increase the risk of hypoglycemia.
Clinical research suggests that Panax ginseng might decrease blood glucose levels. Insulin dose adjustments might be necessary in patients taking Panax ginseng; use with caution.

Likelihood Probable Evidence B
Midazolam (Versed)

Theoretically, Panax ginseng may increase the clearance of midazolam.
Midazolam is metabolized by cytochrome P450 3A4 (CYP3A4). Clinical research suggests that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng.

Likelihood Probable Evidence B
Monoamine Oxidase Inhibitors (Maois)

Theoretically, Panax ginseng can interfere with MAOI therapy.
Concomitant use of Panax ginseng with phenelzine (Nardil) is associated with insomnia, headache, tremors, and hypomania.

Likelihood Probable Evidence D
Nifedipine (Procardia)

Theoretically, taking Panax ginseng with nifedipine might increase serum levels of nifedipine and the risk of hypotension.
Preliminary clinical research shows that concomitant use can increase serum levels of nifedipine in healthy volunteers. This might cause the blood pressure lowering effects of nifedipine to be increased when taken concomitantly with Panax ginseng.

Likelihood Possible Evidence B
Qt Interval-Prolonging Drugs

Theoretically, Panax ginseng has an additive effect with drugs that prolong the QT interval and potentially increase the risk of ventricular arrhythmias. However, research is conflicting.
Clinical research shows that short-term use of Panax ginseng can increase the QT interval. However, no changes in QT interval have been identified with prolonged use.

Likelihood Possible Evidence B
Raltegravir (Isentress)

Theoretically, taking Panax ginseng with raltegravir might increase the risk of liver toxicity.
A case report suggests that concomitant use of Panax ginseng with raltegravir can increase serum levels of raltegravir, resulting in elevated liver enzymes levels.

Likelihood Possible Evidence D
Selegiline (Eldepryl)

Theoretically, Panax ginseng might increase or decrease levels of selegiline, possibly altering the effects and side effects of selegiline.
Animal research shows that taking selegiline with a low dose of Panax ginseng extract (1 gram/kg) reduces selegiline bioavailability, while taking a high dose of Panax ginseng extract (3 grams/kg) increases selegiline bioavailability. More research is needed to confirm these effects.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Panax ginseng might affect the clearance of warfarin. However, this interaction appears to be unlikely.
There has been a single case report of decreased effectiveness of warfarin in a patient who also took Panax ginseng. However, it is questionable whether Panax ginseng was the cause of this decrease in warfarin effectiveness. Some research in humans and animals suggests that Panax ginseng does not affect the pharmacokinetics of warfarin. However, other research in humans suggests that Panax ginseng might modestly increase the clearance of the S-warfarin isomer. More evidence is needed to determine whether Panax ginseng causes a significant interaction with warfarin.

Likelihood Unlikely Evidence B
Fexofenadine (Allegra)

Theoretically, Panax ginseng might decrease blood levels of oral or intravenous fexofenadine.
Animal research suggests that taking Panax ginseng in combination with oral or intravenous fexofenadine may reduce the bioavailability of fexofenadine. Some scientists have attributed this effect to the ability of Panax ginseng to increase the expression of P-glycoprotein.

Likelihood Possible Evidence D
Lopinavir/Ritonavir (Kaletra)

Although Panax ginseng has demonstrated variable effects on cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir, Panax ginseng is unlikely to alter levels of lopinavir/ritonavir.
Lopinavir is metabolized by CYP3A4 and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Panax ginseng has shown variable effects on CYP3A4 activity in humans. However, taking Panax ginseng (Vitamer Laboratories) 500 mg twice daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in 12 healthy volunteers.

Likelihood Unlikely Evidence B
Panax ginseng full monograph & interactions

Vitamin E8 drug types · 764 drugs

Alkylating Agents

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

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence B
Antitumor Antibiotics

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

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

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

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

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

Likelihood Possible Evidence D
Selumetinib (Koselugo)

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

Likelihood Possible Evidence D
Warfarin (Coumadin)

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

Likelihood Possible Evidence B
Niacin

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

Likelihood Possible Evidence A
Vitamin E full monograph & interactions

Phosphotidyl Serine2 drug types · 219 drugs

Anticholinergic Drugs

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

Likelihood Possible Evidence B
Cholinergic Drugs

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

Likelihood Possible Evidence B
Phosphotidyl Serine 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

Acetyl-L-Carnitine4 drug types · 203 drugs

Acenocoumarol (Sintrom)

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

Likelihood Possible Evidence D
Serotonergic Drugs

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

Likelihood Possible Evidence D
Thyroid Hormone

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

Likelihood Probable Evidence B
Warfarin (Coumadin)

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

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

Coenzyme Q103 drug types · 198 drugs

Alkylating Agents

Coenzyme Q10 has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals.
Theoretically, antioxidants such as coenzyme Q10 might protect tumor cells from chemotherapeutic agents that work by inducing oxidative stress, such as alkylating agents (e.g., cyclophosphamide) and radiation therapy. The clinical importance of this interaction is unknown.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Coenzyme Q10 is chemically similar to menaquinone and might have vitamin K-like procoagulant effects, which could decrease the effects of warfarin.
Concomitant use of coenzyme Q10 and warfarin might reduce the anticoagulant effects of warfarin. Four cases of decreased warfarin efficacy thought to be due to coenzyme Q10 have been reported. However, there is some preliminary clinical research that suggests coenzyme Q10 might not significantly decrease the effects of warfarin in patients who have a stable INR.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, coenzyme Q10 might have additive effects with antihypertensive drugs.
Some clinical research shows that coenzyme Q10 can significantly lower blood pressure, although other studies have shown conflicting results.

Likelihood Possible Evidence B
Coenzyme Q10 full monograph & interactions

Folic Acid7 drug types · 40 drugs

5-Fluorouracil

Theoretically, high doses of folic acid might increase the toxicity of 5-fluorouracil.
Increases in gastrointestinal side effects of 5-fluorouracil, such as stomatitis and diarrhea, have been described in two clinical studies when leucovorin, a form of folic acid, was administered with 5-fluorouracil.

Likelihood Possible Evidence D
Capecitabine (Xeloda)

Use of high-dose folic acid might contribute to capecitabine toxicity.
Clinical research suggests that higher serum folate levels are associated with an increased risk for moderate or severe toxicity during capecitabine-based treatment for colorectal cancer. Additionally, in one case report, taking folic acid 15 mg daily might have contributed to increased toxicity, including severe diarrhea, vomiting, edema, hand-foot syndrome, and eventually death, in a patient prescribed capecitabine.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Folic acid might reduce the efficacy of methotrexate as a cancer treatment when given concurrently.
Methotrexate exerts its cytotoxic effects by preventing conversion of folic acid to the active form needed by cells. There is some evidence that folic acid supplements reduce the efficacy of methotrexate in the treatment of acute lymphoblastic leukemia, and theoretically they could reduce its efficacy in the treatment of other cancers. Advise cancer patients to consult their oncologist before using folic acid supplements. In patients treated with long-term, low-dose methotrexate for rheumatoid arthritis (RA) or psoriasis, folic acid supplements can reduce the incidence of side effects, without reducing efficacy.

Likelihood Probable Evidence B
Phenobarbital (Luminal)

Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of phenobarbital and worsening seizure control. Monitor closely for increased seizure activity.

Likelihood Probable Evidence B
Phenytoin (Dilantin)

Folic acid might reduce serum levels of phenytoin in some patients.
Folic acid may be a cofactor in phenytoin metabolism. Folic acid, in doses of 1 mg daily or more, can reduce serum levels of phenytoin in some patients. Increases in seizure frequency have been reported. If folic acid supplements are added to established phenytoin therapy, monitor serum phenytoin levels closely. If phenytoin and folic acid are started at the same time and continued together, adverse changes in phenytoin pharmacokinetics are avoided. Note that phenytoin also reduces serum folate levels.

Likelihood Probable Evidence B
Primidone (Mysoline)

Folic acid might have antagonistic effects on primidone and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of primidone and worsening seizure control. Monitor closely for increased seizure activity. Note that primidone also reduces serum folate levels.

Likelihood Probable Evidence B
Pyrimethamine (Daraprim)

Folic acid might antagonize the effects of pyrimethamine.
Folic acid can antagonize the antiparasitic effects of pyrimethamine against toxoplasmosis and Pneumocystis carinii pneumonia. Folic acid doesn't antagonize the effects of pyrimethamine in the treatment of malaria, because malarial parasites cannot use exogenous folic acid. Use folinic acid as an alternative to folic acid when indicated.

Likelihood Probable Evidence D
Folic Acid full monograph & interactions

Vitamin B121 drug type · 20 drugs

Metformin (Glucophage)

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

Likelihood Possible Evidence A
Vitamin B12 full monograph & interactions

Thiamine1 drug type · 3 drugs

Trimethoprim (Proloprim)

Trimethoprim might increase blood levels of thiamine.
In vitro, animal, and clinical research suggest that trimethoprim inhibits intestinal thiamine transporter ThTR-2, hepatic transporter OCT1, and renal transporters OCT2, MATE1, and MATE2, resulting in paradoxically increased thiamine plasma concentrations.

Likelihood Probable Evidence B
Thiamine full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Clearer Thinking Grapefruit Flavor, from the product label.

Instavit

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Name
Instavit US LLC
Street Address
PO Box 1351
City
Walled Lake
State
MI
ZipCode
48390
Phone Number
888-450-3639
Web Address
www.instavit.com
Pharmacist Counseling Corner

Clearer Thinking Grapefruit Flavor by Instavit: Common Questions

Does Clearer Thinking Grapefruit Flavor by Instavit interact with any medications?
Yes. Based on its ingredients, Clearer Thinking Grapefruit Flavor has a known interaction with 1,807 medications, including 14 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Clearer Thinking Grapefruit Flavor contains 11 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.

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The Full Monographs Behind Clearer Thinking Grapefruit Flavor’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

Folic Acid

Interacts with 40 drugs

Folic acid is the man-made form of vitamin B9 and is one of the most well-studied supplements, especially for preventing serious birth defects when taken before and during early pregnancy. I...

Read the full Folic Acid monograph → Herb & supplement monograph

Vitamin B12

Interacts with 20 drugs

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

Read the full Vitamin B12 monograph → Herb & supplement monograph

Vitamin E

Interacts with 764 drugs

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

Read the full Vitamin E monograph → Herb & supplement monograph

Thiamine

Interacts with 3 drugs

Thiamine (vitamin B1) is an essential nutrient your body needs to turn food into energy and to keep your nerves and heart healthy. Most people get enough from food, but supplements are clear...

Read the full Thiamine monograph → Herb & supplement monograph

Acetyl-l-carnitine

Interacts with 203 drugs

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

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

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

Coenzyme Q10

Interacts with 198 drugs

CoQ10 is a vitamin-like substance your body makes naturally that helps cells produce energy and acts as an antioxidant. It is generally well tolerated and is most studied for heart condition...

Read the full Coenzyme Q10 monograph → Herb & supplement monograph

Ginkgo

Interacts with 1,266 drugs

Ginkgo is one of the world's most popular herbal supplements, mostly taken to support memory and circulation. The evidence for these uses is mixed and generally weak, and it is not proven to...

Read the full Ginkgo monograph → Herb & supplement monograph

Phosphatidylserine

Interacts with 219 drugs

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

Read the full Phosphatidylserine monograph → Herb & supplement monograph

Panax Ginseng

Interacts with 1,130 drugs

Panax ginseng is a popular traditional herb used to boost energy, ease stress, and support overall wellness, though scientific evidence is mixed and mostly preliminary. It is generally well...

Read the full Panax Ginseng monograph →
Sources

Sources & How We Checked

Clearer Thinking Grapefruit Flavor'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 642 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
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  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 →

Folic Acid 56 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol 1993;28:466-9. PubMed
  3. Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41. PubMed
  4. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed
  5. Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726-35. PubMed
  6. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-6. PubMed
  7. Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: Before and after folic acid administration. Epilepsia 1992;33:712-20. PubMed
  8. Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41:1125-9. PubMed
  9. Leeb BF, Witzmann G, Ogris E, et al. Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients. Clin Exp Rheumatol 1995;13:459-63.
  10. Morgan SL, Baggott JE, Lee JY, Alarcón GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease preventi
  11. Dijkmans BA. Folate supplementation and methotrexate. Br J Rheumatol 1995;34:1172-4. PubMed
  12. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
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  14. Amer College of Rheumatology ad hoc committee on clinical guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723-31. DOI
  15. Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc 2000;100:88-94. PubMed
  16. 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
  17. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-78.
  18. Antony AC. Megaloblastic Anemias. In: Hoffman R, Benz Jr EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone 2000: 451-79.
  19. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96. DOI
  20. Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.
  21. Ortiz Z, Shea B, Suarez Almazor M, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis (Cochrane Review). Cochrane Database Syst Rev 2000;2:CD000951. PubMed
  22. Van Delden C, Hirschel B. Folinic acid supplements to pyrimethamine-sulfadiazine for Toxoplasma encephalitis are associated with better outcome (letter). J Infect Dis 1996;173:1294-5. PubMed
  23. Schroder H, Clausen N, Ostergard E, Pressler T. Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia. Ped Hematol Oncol 1986;3:241-7. PubMed
  24. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673-81. PubMed
  25. Morris MC, Evans DA, Bienias JL, et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 2005;62:641-5. PubMed
  26. Bonaa KH, Njolstad I, Ueland PM, et al. NORVIT: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Enlg J Med 2006;354:1578-88. PubMed
  27. 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
  28. Figueiredo JC, Grau MV, Haile RW, et al. Folic acid and risk of prostate cancer: Results from a randomized clinical trial. J Natl Cancer Inst 2009;101:432-5. PubMed
  29. Clippe C, Freyer G, Milano G, Trillet-Lenoir V. Lethal toxicity of capecitabine due to abusive folic acid prescription. Clin Oncol (R Coll Radiol) 2003;15:299-300. PubMed
  30. Bedford Laboratories. Leucovorin calcium [package insert]. Bedford, OH. September 2008. Available at: http://www.bedfordlabs.com/BedfordLabsWeb/products/inserts/LCV-P02.pdf.
  31. Ebbing M, Bonaa KH, Nygard O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009;302:2119-26.
  32. Haberg, S. E., London, S. J., Stigum, H., Nafstad, P., and Nystad, W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis.Child 2009;94(3):180-184. PubMed
  33. Whitrow, M. J., Moore, V. M., Rumbold, A. R., and Davies, M. J. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol. 12-15-2009;170(12):1486-1493. PubMed
  34. Collin, S. M., Metcalfe, C., Refsum, H., Lewis, S. J., Zuccolo, L., Smith, G. D., Chen, L., Harris, R., Davis, M., Marsden, G., Johnston, C., Lane, J. A., Ebbing, M., Bonaa, K. H., Nygard, O., Ueland, P. M., Grau, M. V., Baron, J. A., Donovan, J. L., Nea
  35. Baggott, J. E., Oster, R. A., and Tamura, T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol. 2012;36(1):78-81. PubMed
  36. 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
  37. 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
  38. Taneja S, Strand TA, Kumar T, et al. Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial. Am J Clin Nutr 2013;98(3):731-7. PubMed
  39. van Wijngaarden JP, Swart KM, Enneman AW, et al. Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial. Am J Clin
  40. Qin X, Fan F, Cui Y, Chen F, Chen Y, Cheng X, Li Y, Wang B, Xu X, Xu X, Huo Y, Wang X. Folic acid supplementation with and without vitamin B6 and revascularization risk: a meta-analysis of randomized controlled trials. Clin Nutr. 2014;33(4):603-12. PubMed
  41. Crider KS, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am J Clin Nutr. 2013;98(5):1272-81. PubMed
  42. Matsubara S, Imai K, Murayama K, Higashizawa T. Severe liver dysfunction during nausea and vomiting of pregnancy: folic acid supplement as a suggested culprit. J Obstet Gynaecol. 2012;32(7):701-2. PubMed
  43. Qin X, Cui Y, Shen L, Sun N, Zhang Y, Li J, Xu X, Wang B, Xu X, Huo Y, Wang X. Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials. Int J Cancer. 2013 1;133(5):1033-41. PubMed
  44. Tio M, Andrici J, Cox MR, Eslick GD. Folate intake and the risk of prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2014;17(3):213-9. PubMed
  45. Tomaszewski JJ, Richman EL, Sadetsky N, O'Keefe DS, Carroll PR, Davies BJ, Chan JM. Impact of folate intake on prostate cancer recurrence following definitive therapy: data from CaPSURE. J Urol. 2014;191(4):971-6. PubMed
  46. Valera-Gran D, García de la Hera M, Navarrete-Muñoz EM, Fernandez-Somoano A, Tardón A, Julvez J, Forns J, Lertxundi N, Ibarluzea JM, Murcia M, Rebagliato M, Vioque J; Infancia y Medio Ambiente (INMA) Project. Folic acid supplements during pregnancy and ch
  47. Van Der Woude DA, De Vries J, Van Wijk EM, Verzijl JM, Pijnenborg JM. A randomized controlled trial examining the addition of folic acid to iron supplementation in the treatment of postpartum anemia. Int J Gynaecol Obstet. 2014;126(2):101-5. PubMed
  48. Vila-Nova C, Wehby GL, Queirós FC, Chakraborty H, Félix TM, Goco N, Moore J, Gewehr EV, Lins L, Affonso CM, Murray JC. Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil. J Perinat Med. 201 PubMed
  49. Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J, Manson JE, Hankey GJ, Spence JD, Galan P, Bønaa KH, Jamison R, Gaziano JM, Guarino P, Baron JA, Logan RF, Giovannucci EL, den Heijer M, Ueland PM, Bennett D, Collins R, Peto R; B-V
  50. Wehby GL, Félix TM, Goco N, Richieri-Costa A, Chakraborty H, Souza J, Pereira R, Padovani C, Moretti-Ferreira D, Murray JC. High dosage folic acid supplementation, oral cleft recurrence and fetal growth. Int J Environ Res Public Health. 2013 4;10(2):590-6 PubMed
  51. Fanidi A, Carreras-Torres R, Larose TL, et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019 Sep 15;145(6):1499-1503. PubMed
  52. Liu J, Li Z, Ye R, Liu J, Ren A. Periconceptional folic acid supplementation and risk of parent-reported asthma in children at 4-6 years of age. ERJ Open Res. 2020;6(1):00250-2019. PubMed
  53. Houghton LA, Sherwood KL, Pawlosky R, Ito S, O'Connor DL. [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr. 2006 Apr;83(4):842-50. PubMed
  54. Houghton LA, Yang J, O'Connor DL. Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements. Am J Clin Nutr. 2009 Jan;89(1):216-20. PubMed
  55. Chan SL, Chan AWH, Mo F, et al. Association Between Serum Folate Level and Toxicity of Capecitabine During Treatment for Colorectal Cancer. Oncologist. 2018 Dec;23(12):1436-1445. PubMed
  56. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T

See these in context on the Folic Acid monograph →

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

See these in context on the Vitamin B12 monograph →

Vitamin E 64 references
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Parts of this content are provided by the Therapeutic Research Center, LLC.

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

© 2021 Therapeutic Research Center, LLC

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