Major interaction on record — check this product against your medications before combining. Based on 18 of 19 ingredients. Check your meds →
Dietary supplement

Cleanse Ingredients & Drug Interactions

by Wellthy Nutraceuticals

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

Cleanse is a dietary supplement by Wellthy Nutraceuticals with 19 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,402 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Ginger root extract, Milk Thistle powder, Grape seed extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Cleanse by Wellthy Nutraceuticals

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

From our pharmacy team — supplement deep dive

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 19 of its 19 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Cleanse contains 19 active ingredients. The B vitamins—Vitamin B6, Folic Acid, Riboflavin, and Thiamine—support energy and nerve function.

Alpha Lipoic Acid, Selenium, and Resveratrol are antioxidants. L-Carnitine supports heart and muscle metabolism.

The herbal components include Dong Quai, Milk Thistle powder, Cranberry Whole Fruit Extract, Dandelion extract, Agaricus mushroom extract, and Ginger root extract. Lutein supports eye health.

Pantothenic Acid (another B vitamin) and 3,3'-Diindolylmethane (a compound from cruciferous vegetables) round out the blend. One ingredient, DigeSeb Plus a Proprietary Enzyme Blend, is a proprietary blend we cannot fully characterize.

The capsules contain cellulose, rice flour powder, and magnesium stearate as inactive ingredients.

Does it work?

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

The graded evidence we hold for these ingredients covers different conditions than the ones this product is marketed for, so there's no established rating for its stated use.

Why this rating?
  • The label markets this product for: Gentle daily full body detox.
  • We looked for evidence on: Liver health, Digestive support, Antioxidant support, General wellness.
  • The closest evidence on file: Resveratrol is rated "Possibly Ineffective" for Nonalcoholic fatty liver disease (NAFLD) (Natural Medicines).
  • Also on file: Alpha-lipoic Acid is rated "Possibly Ineffective" for Alcohol-related liver disease.
  • Also on file: Milk Thistle is rated "Insufficient Reliable Evidence To Rate" for Alcohol-related liver disease, Metabolic dysfunction-associated steatotic liver disease (MASLD), Nonalcoholic fatty liver disease (NAFLD), Toxin-induced liver damage, and more.

The data shows varying levels of evidence for different uses. Vitamin B6 is effective for sideroblastic anemia and deficiency, and likely effective for lowering homocysteine; it's possibly effective for pregnancy-induced nausea.

Folic Acid is effective for folate deficiency and likely effective for preventing neural tube birth defects and managing methotrexate toxicity. Thiamine is effective for thiamine deficiency and Wernicke-Korsakoff syndrome.

Several ingredients are rated possibly effective for specific conditions: Alpha Lipoic Acid for diabetic nerve pain, hyperlipidemia, and obesity; L-Carnitine for high cholesterol, heart failure, and chest pain; Milk Thistle for type 2 diabetes; Cranberry for urinary tract infections; Ginger for pregnancy nausea, period pain, and osteoarthritis; Grape Seed Extract for chronic venous insufficiency; Lutein for age-related macular degeneration and cataracts; and Resveratrol for obesity and allergic rhinitis. For many other uses listed in the formula—such as Dong Quai for various conditions, Selenium for certain health states, and Agaricus mushroom for multiple conditions—the evidence is insufficient to rate.

Riboflavin, Pantothenic Acid, and Dandelion have no established effectiveness ratings in the data we hold.

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 18 of the 18 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 18 of 18.
  • General safety write-ups exist for 18 of 18.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated at standard doses. Vitamin B6 is safe in normal food and supplement amounts, though high doses over time can harm nerves (sensory neuropathy); it's likely safe in pregnancy but possibly unsafe at high doses.

Folic Acid is generally safe at recommended doses and likely safe in pregnancy for birth-defect prevention. Riboflavin, Thiamine, and Pantothenic Acid are considered very safe at typical levels.

Alpha Lipoic Acid is generally well tolerated but should be avoided in pregnancy and breastfeeding due to insufficient data. L-Carnitine can cause stomach upset and a fishy odor at high doses and is not well studied in pregnancy or breastfeeding.

Dong Quai may increase bleeding and cause sun sensitivity; it is possibly unsafe in pregnancy and should be avoided while breastfeeding. Milk Thistle is generally well tolerated but should be avoided in pregnancy; safety during breastfeeding requires caution.

Cranberry is likely safe in pregnancy and breastfeeding at food amounts, though concentrated supplements need more study. Selenium is safe within the upper intake limit of 400 mcg daily but is toxic in excess; high-dose supplements should be avoided in pregnancy unless advised by a doctor.

Dandelion is generally well tolerated as food but less studied at supplement strength; limited data exist for pregnancy and breastfeeding. Agaricus mushroom is generally tolerated as food but should be avoided as a supplement in pregnancy and breastfeeding due to insufficient data.

Ginger is generally well tolerated and likely safe in pregnancy for morning sickness (under doctor guidance) and likely safe while breastfeeding. Grape Seed Extract is likely safe in pregnancy and breastfeeding when used as food; concentrated supplements need more study.

Lutein and Resveratrol are likely safe in pregnancy and breastfeeding. Diindolylmethane is generally well tolerated short-term but should be avoided in pregnancy and breastfeeding due to lack of data.

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

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

Why this rating?
  • 16 of the 18 matched ingredients can interact with medications — Milk Thistle, Resveratrol, Grape, Dandelion, Alpha-lipoic Acid, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; lithium; Parkinson's medications.
  • For scale: 1,403 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.

Check with your pharmacist or doctor before taking this product if you use blood thinners or antiplatelet drugs (Warfarin, other anticoagulants, aspirin, clopidogrel), seizure medications (Phenytoin, Phenobarbital, Primidone), diabetes medications, thyroid hormone replacement, cancer medications, or drugs metabolized by liver enzymes (including statins like atorvastatin, calcium channel blockers like nifedipine, and immunosuppressants). The most serious concern is a Major-severity interaction between Dong Quai and Warfarin that increases bleeding risk.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with no established evidence rating for its marketed use. Major medication interactions have been identified, and safety information is well characterized.

Cleanse is a complex multi-ingredient supplement with a significant interaction profile, especially if you take blood thinners, seizure medications, diabetes drugs, or medications metabolized by liver enzymes. If you're on any prescription medications—particularly warfarin, phenytoin, phenobarbital, or cancer treatments—talk with your pharmacist or doctor before using this product.

Most individual ingredients are generally well tolerated, but their combination and your personal medication history matter.

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

Assessment coverage: 18 of 19 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated May 22, 2021.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Cleanse, straight from the product label.

Brand Wellthy Nutraceuticals
Barcode (UPC) 860000027618
Net contents 60 Veggie Cap(s)
Market status On market
Date entered into DSLD May 22, 2021
DSLD ID 248176
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegan, Vegetarian, Adult (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Cleanse by Wellthy Nutraceuticals, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
30
UPC/BARCODE
860000027618
IngredientAmount% DV
Vitamin B65 mg250%
Folic Acid200 mcg50%
Alpha Lipoic Acid5 mg--
Riboflavin5 mg294%
Thiamine5 mg333%
Pantothenic Acid6 mg6%
L-Carnitine L-Tartrate500 mg--
Dong Quai10 mg--
Milk Thistle powder10 mg--
Cranberry Whole Fruit Extract10 mg--
Selenium100 mcg143%
Dandelion extract400 mg--
DigeSeb Plus a Proprietary Enzyme Blend100 mg--
Agaricus bisporus extract100 mg--
Ginger root extract100 mg--
Grape seed extract20 mg--
3,3'-Diindolymethane15 mg--
Lutein powder1 mg--
Resveratrol 20% powder1 mg--

Other ingredients: Cellulose, Plant, Rice Flour powder, Magnesium Stearate

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.
Precautions

This product is not intended for use by any persons under age 18, who are pregnant or lactating, or have serious medical conditions.

This product is not intended for use by any persons under age 18, who are pregnant or lactating, or have serious medical conditions.

Keep out of reach of children.

Warning: Do not exceed recommended dose listed. All persons should consult a physician before using dietary supplements, as individuals may have different supplement needs. Consumption of this product that is inconsistent with recommended usage may produce adverse side effects. Discontinue use and contact physician immediately if you experience any adverse effects.

FDA Disclaimer Statement

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

General Statements

Instagram Twitter Facebook @imwellthy 1 product = 1 meal For every wellthy product you purchase we provide a meal to someone in need through local food banks.

Formulation

Gentle daily full body detox

All natural 60 veggie caps

Vegan

GMP Certified Good Manufacturing Practice Made In U.S.A.

Gluten Free Dairy Free Free Of Banned Substances

Formula

Paleo Friendly

Suggested/Recommended/Usage/Directions

Suggested Use: Take two capsule once a day with at least 8oz of water and after a meal to cleanse your body of toxins and decrease bloating and water weight.

For complete wellness take with: Sweat Fat burner & thermogenic Sleep Night time fat burn & sleep aid Ketofuel Instant ketosis and energy

Seals/Symbols

GMP Certified Good Manufacturing Practice Made In U.S.A.

See for yourself

Cleanse by Wellthy Nutraceuticals label

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

What’s inside

The Ingredients in Cleanse by Wellthy Nutraceuticals

These are the 19 active ingredients this product is made of. Select any to open its full monograph.

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

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

Vitamin B6

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

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

Vitamin B6 monograph & interactions

Folic Acid

Interacts with
40 drugs
200 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

Alpha Lipoic Acid

Interacts with
263 drugs
5 mg per serving

Alpha-lipoic acid (ALA) is an antioxidant made naturally by the body and found in small amounts in foods. It is most studied for diabetic nerve pain,...

Alpha Lipoic Acid monograph & interactions

Riboflavin

Interacts with
20 drugs
5 mg per serving

Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally...

Riboflavin monograph & interactions

Thiamine

Interacts with
3 drugs
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

Pantothenic Acid

No known
interactions
6 mg per serving Form: D-Calcium Pantothenate

Pantothenic acid is vitamin B5, an essential nutrient your body uses to turn food into energy. True deficiency is very rare because it is found in nea...

Pantothenic Acid monograph & interactions

L-Carnitine L-Tartrate

Interacts with
19 drugs
500 mg per serving

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

L-Carnitine L-Tartrate monograph & interactions

Dong Quai

Interacts with
163 drugs
10 mg per serving

Dong Quai is a traditional Chinese herb often called "female ginseng" and is mostly used for menstrual and menopausal complaints. High-quality scienti...

Dong Quai monograph & interactions

Milk Thistle powder

Interacts with
954 drugs
10 mg per serving

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin....

Milk Thistle powder monograph & interactions

Cranberry Whole Fruit Extract

Interacts with
712 drugs
10 mg per serving

Cranberry is best known for helping to prevent repeated urinary tract infections (UTIs) in some people, and the evidence here is moderate but mixed. I...

Cranberry Whole Fruit Extract monograph & interactions

Selenium

Interacts with
321 drugs
100 mcg per serving Form: Selenium Bisglycinate Complex

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who...

Selenium monograph & interactions

Dandelion extract

Interacts with
457 drugs
400 mg per serving

Dandelion is a common plant used in food and traditional medicine, often promoted as a natural 'water pill' and digestive aid. Human evidence for thes...

Dandelion extract monograph & interactions

DigeSeb Plus a Proprietary Enzyme Blend

100 mg per serving Form: Amylases, Cellulase, Diastase, HemiSEB, Invertase, Lactase, Lipase, Protease Blend

Agaricus bisporus extract

Interacts with
86 drugs
100 mg per serving Form: Polysaccharides

Agaricus mushroom (often Agaricus blazei/subrufescens) is a culinary and medicinal mushroom studied mostly for possible immune and antioxidant effects...

Agaricus bisporus extract monograph & interactions

Ginger root extract

Interacts with
1,007 drugs
100 mg per serving Form: Gingerols

Ginger is a widely used culinary spice with a long history in traditional medicine, and it has the strongest evidence for helping with nausea and vomi...

Ginger root extract monograph & interactions

Grape seed extract

Interacts with
910 drugs
20 mg per serving Form: Proanthocyanidins

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and b...

Grape seed extract monograph & interactions

3,3'-Diindolymethane

Interacts with
269 drugs
15 mg per serving

Diindolylmethane (DIM) is a compound made when your body digests cruciferous vegetables, and it is sold as a supplement mainly for hormone balance and...

3,3'-Diindolymethane monograph & interactions

Lutein powder

No known
interactions
1 mg per serving Form: Tagetes erecta L.

Lutein is a plant-based antioxidant pigment that concentrates in the eye, and the best evidence suggests it (often combined with zeaxanthin) may help...

Lutein powder monograph & interactions

Resveratrol 20% powder

Interacts with
822 drugs
1 mg per serving Form: Japanese Knotweed

Resveratrol is a plant compound found in red grapes, berries, and peanuts that is popular for heart health, anti-aging, and antioxidant support. While...

Resveratrol 20% powder monograph & interactions

Other (inactive) ingredients: Cellulose, Plant, Rice Flour powder, Magnesium Stearate. These complete the product’s ingredient list but are not active constituents.

Interaction report

Cleanse by Wellthy Nutraceuticals Drug Interactions

Want to check YOUR meds against Cleanse?

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
1,402Drugs
2 Major 1,366 Moderate 34 Minor

Each ingredient & the kinds of drugs it affects

For each ingredient in Cleanse 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.

Ginger root extract14 drug types · 1,007 drugs

Anticoagulant/Antiplatelet Drugs

Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation. However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials. Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels.

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

Ginger might increase or decrease the levels of CYP3A4 substrates.
In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity. Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Losartan (Cozaar)

Theoretically, ginger might increase levels of losartan and the risk of hypotension.
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan. It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

Likelihood Possible Evidence D
Nifedipine (Procardia)

Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.

Likelihood Possible Evidence D
Phenprocoumon (Marcoumar, Others)

Ginger might increase the risk of bleeding with phenprocoumon.
Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Ginger might increase the risk of bleeding with warfarin.
Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation. In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin. In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen. A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months. However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. Until more is known, monitor INRs closely in patients taking large amounts of ginger.

Likelihood Possible Evidence B
Calcium Channel Blockers

Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects. Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone.

Likelihood Unlikely Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time.

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

Theoretically, ginger might increase the levels of CYP1A2 substrates.
In vitro research shows that ginger inhibits CYP1A2 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2B6 (Cyp2B6) Substrates

Theoretically, ginger might increase the levels of CYP2B6 substrates.
In vitro research shows that ginger inhibits CYP2B6 activity. However, this interaction has not been reported in humans.

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

Theoretically, ginger might increase the levels of CYP2C9 substrates.
In vitro research shows that ginger inhibits CYP2C9 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Metronidazole (Flagyl)

Theoretically, ginger might increase levels of metronidazole.
In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced.

Likelihood Possible Evidence D

Milk Thistle powder17 drug types · 954 drugs

Antidiabetes Drugs

Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
Clinical research shows that milk thistle extract, alone or along with tree turmeric extract, can lower blood glucose levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, including those already taking antidiabetes drugs. Additionally, animal research shows that milk thistle extract increases the metformin maximum plasma concentration and area under the curve and decreases the renal clearance of metformin, due to inhibition of the multi-drug and toxin extrusion protein 1 (MATE1) renal tubular transport protein.

Likelihood Possible Evidence B
Cytochrome P450 2B6 (Cyp2B6) Substrates

Theoretically, milk thistle might inhibit CYP2B6.
An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels.

Likelihood Possible Evidence D
Glucuronidated Drugs

Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase, although the significance of this effect is unclear.

Likelihood Possible Evidence D
Ledipasvir

Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination.

Likelihood Possible Evidence D
Morphine

Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.
Animal research shows that milk thistle reduces serum levels of morphine by up to 66%. In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.

Likelihood Possible Evidence D
Raloxifene (Evista)

Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.
Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines.

Likelihood Possible Evidence D
Sirolimus (Rapamune)

Milk thistle might decrease the clearance of sirolimus.
Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients. It is unclear if this interaction occurs in patients without hepatic impairment.

Likelihood Possible Evidence B
Sofosbuvir (Solvaldi)

Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.
Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion. Whether this interaction occurs in humans is not known.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, milk thistle might increase the effects of warfarin.
In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement. Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin.

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

It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
In vitro research suggests that milk thistle might inhibit CYP2C9. Additionally, 3 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP2C9 substrates, including imatinib and capecitabine. However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide. Differences in results could be due to differences in dosages or formulations utilized.

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

It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
While laboratory research shows conflicting results, pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir. However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine.

Likelihood Unlikely Evidence D
Estrogens

Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
Animal research suggests that a milk thistle extract of silymarin binds to estrogen receptor beta.

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

Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).
Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action, and animal research shows this increases the maximum plasma concentration of pitavastatin and pravastatin. The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin.

Likelihood Unlikely Evidence D
Indinavir (Crixivan)

Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.
One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25%. However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir. Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir.

Likelihood Unlikely Evidence B
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Milk thistle may inhibit one form of OATP, OATP-B1, which could reduce the bioavailability and clinical effects of OATP-B1 substrates.
In vitro research shows that milk thistle inhibits OATP-B1. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are OATP substrates, including sorafenib and methotrexate. OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
In vitro research shows that milk thistle can inhibit P-glycoprotein activity and 1 case report from the World Health Organization (WHO) adverse drug reaction database describes increased abdominal pain in a patient taking milk thistle and the cancer medication vincristine, a P-glycoprotein substrate, though this patient was also taking methotrexate. However, a small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein substrate.

Likelihood Unlikely Evidence B

Grape seed extract9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water. Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

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

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.

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

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.

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

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination.

Likelihood Possible Evidence D
Phenacetin

Grape juice might decrease phenacetin absorption.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2).

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

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.

Likelihood Unlikely Evidence D

Resveratrol 20% powder5 drug types · 822 drugs

Anticoagulant/Antiplatelet Drugs

Resveratrol may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Resveratrol seems to have antiplatelet effects.

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

Theoretically, resveratrol might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that resveratrol can inhibit CYP1A2 enzymes. However, this interaction has not been reported in humans.

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

Theoretically, resveratrol might increase levels of drugs metabolized by CYP2C19.
In vitro research shows that resveratrol can inhibit CYP2C19 enzymes. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Resveratrol might increase levels of drugs metabolized by CYP2E1.
In vitro research suggests that resveratrol inhibits CYP2E1 isoenzyme. Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35%. Chlorzoxazone is used as a probe drug for CYP2E1.

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

Theoretically, resveratrol might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that resveratrol can inhibit the CYP3A4 enzyme. However, clinical research shows that taking resveratrol 3000 mg daily for 8 weeks does not necessitate dose adjustments to medications metabolized by CYP3A4.

Likelihood Possible Evidence D

Cranberry Whole Fruit Extract6 drug types · 712 drugs

Atorvastatin (Lipitor)

Theoretically, cranberry might increase levels and adverse effects of atorvastatin.
In one case report, a patient taking atorvastatin experienced upper back pain, rhabdomyolysis, and abnormal liver function after drinking cranberry juice 16 ounces daily for 2 weeks. Theoretically, this may have been caused by inhibition of cytochrome P450 3A4 (CYP3A4) enzymes by cranberry juice, as atorvastatin is a CYP3A4 substrate. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice. Patients taking atorvastatin should avoid large quantities of cranberry juice.

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

Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.
A case of upper back pain, rhabdomyolysis, and abnormal liver function has been reported for a patient taking atorvastatin, a CYP3A4 substrate, in combination with cranberry juice 16 ounces daily for 2 weeks. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice. Also, animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine, a CYP3A4 substrate, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control.

Likelihood Possible Evidence D
Nifedipine (Procardia)

Theoretically, cranberry might increase the levels and adverse effects of nifedipine.
Animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine treatment, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, cranberry might increase the levels and adverse effects of warfarin. However, research is conflicting.
There is contradictory evidence about the effect of cranberry juice on warfarin. Case reports have linked cranberry juice consumption to increases in the international normalized ratio (INR) in patients taking warfarin, resulting in severe spontaneous bleeding and excessive postoperative bleeding. Daily consumption of cranberry sauce for one week has also been linked to an increase in INR in one case report. In a small study in healthy young males, taking a high dose of 3 grams of cranberry juice concentrate capsules, equivalent to 57 grams of fruit daily, for 2 weeks produced a 30% increase in the area under the INR-time curve after a single 25-mg dose of warfarin. However, 3 very small clinical studies in patients stabilized on warfarin reported that cranberry juice 250 mL once or twice daily for 7 days (27% cranberry juice or pure cranberry juice) or 240 mL once daily for 14 days does not significantly increase INR or affect plasma warfarin levels. The reasons for these discrepant findings are unclear. It is possible that the form and dose of cranberry may play a role, as cranberry extracts and juices contain different constituents. Additionally, an in vitro study evaluating 5 different cranberry juices found varying effects, with only a cranberry concentrate, and not diluted cranberry juices, inhibiting CYP2C9. However, this concentrate did not inhibit CYP2C9 activity in humans.

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

Theoretically, cranberry might increase the levels and adverse effects of CYP2C9 substrates. However, research is conflicting.
There is contradictory evidence about the effect of cranberry on CYP2C9 enzymes. In vitro evidence suggests that flavonoids in cranberry inhibit CYP2C9 enzymes. However, clinical research shows that cranberry juice does not significantly affect the levels, metabolism, or elimination of the CYP2C9 substrates flurbiprofen or diclofenac. Also, in patients stabilized on warfarin, drinking cranberry juice 250 mL daily for 7 days does not significantly increase the anticoagulant activity of warfarin, a CYP2C9 substrate. Additional pharmacokinetic research shows that cranberry juice does not increase peak plasma concentrations or area under the concentration-time curve of warfarin.

Likelihood Unlikely Evidence B
Diclofenac (Voltaren, Others)

Theoretically, cranberry might modestly increase the levels and adverse effects of diclofenac.
In vitro evidence suggests that cranberry juice inhibits diclofenac metabolism by human liver microsomes. However, drinking cranberry juice does not seem to affect diclofenac metabolism in humans.

Likelihood Unlikely Evidence B

Dandelion extract7 drug types · 457 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, taking dandelion root along with anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.
In vitro research suggests that dandelion root inhibits platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, dandelion might increase the risk for hypoglycemia when used with antidiabetes drugs.
Laboratory research suggests that dandelion extract may have moderate alpha-glucosidase inhibitor activity and might also increase insulin secretion. Also, in a case report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemia 2 weeks after beginning to eat salads containing dandelion.

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

Theoretically, dandelion might increase levels of drugs metabolized by CYP1A2.
Laboratory research suggests that dandelion might inhibit CYP1A2. So far, this interaction has not been reported in humans. However, until more is known, watch for an increase in the levels of drugs metabolized by CYP1A2 in patients taking dandelion.

Likelihood Possible Evidence D
Glucuronidated Drugs

Theoretically, dandelion might increase the clearance of drugs that are UDP-glucuronosyltransferase substrates.
There is some preliminary evidence that dandelion might induce UDP-glucuronosyltransferase, a phase II enzyme.

Likelihood Possible Evidence D
Lithium

Theoretically, through diuretic effects, dandelion might reduce excretion and increase levels of lithium.
Animal research suggests that dandelion has diuretic properties. As diuretics can increase serum lithium levels, the dose of lithium might need to be decreased when taken with dandelion.

Likelihood Probable Evidence D
Potassium-Sparing Diuretics

Theoretically, dandelion might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.
Dandelion contains significant amounts of potassium.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, dandelion might lower fluoroquinolone levels.
Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73%. However, this effect has not been reported in humans.

Likelihood Possible Evidence D

Selenium6 drug types · 321 drugs

Anticoagulant/Antiplatelet Drugs

Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity. Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation.

Likelihood Possible Evidence D
Barbiturates

Theoretically, selenium might prolong the sedating effects of barbiturates.
Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates. Selenium seems to prolong the sedative effect of pentobarbital in animal models.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, selenium might interfere with warfarin activity.
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors. Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity.

Likelihood Possible Evidence D
Contraceptive Drugs

Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels. It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium.

Likelihood Possible Evidence B
Niacin

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

Likelihood Possible Evidence A

3,3'-Diindolymethane3 drug types · 269 drugs

Diuretic Drugs

Theoretically, diindolylmethane might increase the risk of hyponatremia if used with sodium-depleting diuretics.
Large doses of diindolylmethane (600 mg daily) have been associated with two cases of asymptomatic hyponatremia in clinical research.

Likelihood Possible Evidence B
Estrogens

Theoretically, diindolylmethane might increase or decrease the effects of estrogens.
Diindolylmethane might have mild estrogenic or antiestrogenic effects. Theoretically, large amounts of diindolylmethane might interfere with hormone replacement therapy.

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

Theoretically, diindolylmethane might lower serum levels of CYP1A2 substrates.
In vitro evidence suggests that diindolylmethane can induce CYP1A2. Theoretically, it might increase metabolism of CYP1A2 substrates and lower serum concentrations. This interaction has not been reported in humans.

Likelihood Unlikely Evidence D

Alpha Lipoic Acid5 drug types · 263 drugs

Alkylating Agents

Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of alkylating agents.
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of chemotherapy drugs that 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 alpha-lipoic acid have on chemotherapy. Advise patients to consult their oncologist before using alpha-lipoic acid.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, alpha-lipoic acid may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro, alpha-lipoic acid inhibits platelet aggregation.

Likelihood Possible Evidence D
Antitumor Antibiotics

Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of antitumor antibiotics.
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of antitumor antibiotic drugs, which work by generating 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 alpha-lipoic acid have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using alpha-lipoic acid.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, alpha-lipoic acid might decrease the effects of thyroid hormone drugs.
Animal research suggests that co-administration of thyroxine with alpha-lipoic acid reduces conversion into the active T3 form.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking alpha-lipoic acid with antidiabetes drugs might increase the risk of hypoglycemia.
Although some small clinical studies have suggested that alpha-lipoic acid can lower blood glucose levels, larger clinical studies in patients with diabetes have shown no clinically meaningful effect. Additionally, co-administration of single doses of alpha-lipoic acid and glyburide or acarbose did not cause detectable drug interactions in healthy volunteers.

Likelihood Unlikely Evidence B

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

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

Likelihood Possible Evidence B
Antihypertensive Drugs

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Levodopa

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

Likelihood Unlikely Evidence D

Dong Quai3 drug types · 163 drugs

Warfarin (Coumadin)

Dong quai may increase the risk of bleeding when used with warfarin.
Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding. In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.
Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components. Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin. However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding. Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.

Likelihood Possible Evidence D
Estrogens

Theoretically, dong quai may reduce the effects of estrogens.
Dong quai has estrogenic effects. Theoretically, concomitant use of large amounts of dong quai might interfere with hormone replacement therapy due to competition for estrogen receptors.

Likelihood Possible Evidence D

Agaricus bisporus extract1 drug type · 86 drugs

Antidiabetes Drugs

Theoretically, taking agaricus mushroom with antidiabetes drugs might increase the risk of hypoglycemia.
In one clinical study in patients with type 2 diabetes who are stabilized on conventional oral hypoglycemic agents, 3 of 29 patients taking an agaricus mushroom extract 500 mg three times daily for 12 weeks reported hypoglycemia, compared to one of 29 patients in the placebo group.

Likelihood Possible Evidence D

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

Riboflavin1 drug type · 20 drugs

Tetracycline Antibiotics

Theoretically, taking riboflavin with tetracycline antibiotics may decrease the potency of these antibiotics.
In vitro research suggests that riboflavin may inhibit the potency of tetracycline antibiotics. It is not clear if this effect is clinically significant, as this interaction has not been reported in humans.

Likelihood Possible Evidence D

L-Carnitine L-Tartrate3 drug types · 19 drugs

Acenocoumarol (Sintrom)

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

Likelihood Possible Evidence D
Thyroid Hormone

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

Likelihood Probable Evidence B
Warfarin (Coumadin)

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

Likelihood Possible Evidence D

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
The maker

Brand information

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

Wellthy Nutraceuticals

See all Wellthy Nutraceuticals products
Name
Wellthy LLC
City
Las Vegas
State
NV
Phone Number
(888) 886-4909
Web Address
www.ImWellthy.com
Pharmacist Counseling Corner

Cleanse by Wellthy Nutraceuticals: Common Questions

Does Cleanse by Wellthy Nutraceuticals interact with any medications?
Yes. Based on its ingredients, Cleanse has a known interaction with 1,402 medications, including 2 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Cleanse contains 19 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take Cleanse if I'm on warfarin?
No—not without talking to your doctor first. Dong Quai in this formula carries a Major-severity interaction with warfarin and can increase bleeding risk. Several other ingredients (Vitamin B6, Alpha Lipoic Acid, Ginger, Milk Thistle, Cranberry, Selenium, L-Carnitine, and Grape Seed Extract) also have documented interactions with blood thinners. Your doctor needs to know about all your medications before you start.
Is it safe to take Cleanse while pregnant?
It depends on the ingredient and dose. Folic Acid and some B vitamins are recommended during pregnancy, but others—such as Alpha Lipoic Acid, Dong Quai, Milk Thistle, Diindolylmethane, and Resveratrol—should be avoided or used only under doctor supervision due to insufficient safety data. Talk to your obstetrician or midwife before taking this product.
Can I take Cleanse if I have type 2 diabetes?
Check with your doctor first. Several ingredients—Alpha Lipoic Acid, Milk Thistle, Dandelion, Agaricus mushroom, and Ginger—may lower blood sugar and increase the risk of low blood sugar (hypoglycemia) if you're already on diabetes medication. Your doctor may need to monitor or adjust your diabetes drug dose.
What does DigeSeb Plus do?
DigeSeb Plus is listed as a proprietary enzyme blend in this formula, but we don't have interaction or effectiveness data on file for it, so we can't tell you what it does or whether it affects medications. Ask your pharmacist if you'd like more details about this ingredient.
Is Cleanse effective for detox or cleansing?
The ingredients have different roles—some are vitamins, some are antioxidants, and some are herbal compounds—but no single ingredient in this product is rated as effective specifically for 'detox' or 'cleansing.' Many have insufficient evidence or are only possibly effective for other specific uses. Your body's liver and kidneys already do the detoxifying work.
What are the most common side effects of taking Cleanse?
Individual ingredients can cause stomach upset (nausea, diarrhea, heartburn), headache, and changes in urine color (from Riboflavin). Ginger may cause a burning sensation in the mouth. Higher doses of Vitamin B6 increase the risk of nerve damage. Most side effects are mild at typical supplement doses, but stop and call your pharmacist if you have unusual symptoms.

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

Not sure if Cleanse is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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

Cleanse label
Go deeper

The Full Monographs Behind Cleanse’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

Alpha-lipoic Acid

Interacts with 263 drugs

Alpha-lipoic acid (ALA) is an antioxidant made naturally by the body and found in small amounts in foods. It is most studied for diabetic nerve pain, where some evidence suggests it may help...

Read the full Alpha-lipoic Acid monograph →
Herb & supplement monograph

Riboflavin

Interacts with 20 drugs

Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally very safe at typical doses, and the stro...

Read the full Riboflavin 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

Pantothenic Acid

Pantothenic acid is vitamin B5, an essential nutrient your body uses to turn food into energy. True deficiency is very rare because it is found in nearly all foods, and most people meet thei...

Read the full Pantothenic Acid monograph →
Herb & supplement monograph

L-carnitine

Interacts with 19 drugs

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

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

Dong Quai

Interacts with 163 drugs

Dong Quai is a traditional Chinese herb often called "female ginseng" and is mostly used for menstrual and menopausal complaints. High-quality scientific evidence that it works for these use...

Read the full Dong Quai monograph →
Herb & supplement monograph

Milk Thistle

Interacts with 954 drugs

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin. While it is generally well tolerated, th...

Read the full Milk Thistle monograph →
Herb & supplement monograph

Cranberry

Interacts with 712 drugs

Cranberry is best known for helping to prevent repeated urinary tract infections (UTIs) in some people, and the evidence here is moderate but mixed. It is not a reliable treatment for an act...

Read the full Cranberry monograph →
Herb & supplement monograph

Selenium

Interacts with 321 drugs

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who eat a varied diet get enough, and supple...

Read the full Selenium monograph →
Herb & supplement monograph

Dandelion

Interacts with 457 drugs

Dandelion is a common plant used in food and traditional medicine, often promoted as a natural 'water pill' and digestive aid. Human evidence for these uses is very limited, so its benefits...

Read the full Dandelion monograph →
Herb & supplement monograph

Agaricus Mushroom

Interacts with 86 drugs

Agaricus mushroom (often Agaricus blazei/subrufescens) is a culinary and medicinal mushroom studied mostly for possible immune and antioxidant effects. The human evidence is limited and not...

Read the full Agaricus Mushroom monograph →
Herb & supplement monograph

Ginger

Interacts with 1,007 drugs

Ginger is a widely used culinary spice with a long history in traditional medicine, and it has the strongest evidence for helping with nausea and vomiting, including from motion sickness, pr...

Read the full Ginger monograph →
Herb & supplement monograph

Grape

Interacts with 910 drugs

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is he...

Read the full Grape monograph →
Herb & supplement monograph

Diindolylmethane

Interacts with 269 drugs

Diindolylmethane (DIM) is a compound made when your body digests cruciferous vegetables, and it is sold as a supplement mainly for hormone balance and cancer prevention. Although early lab s...

Read the full Diindolylmethane monograph →
Herb & supplement monograph

Lutein

Lutein is a plant-based antioxidant pigment that concentrates in the eye, and the best evidence suggests it (often combined with zeaxanthin) may help slow progression of age-related macular...

Read the full Lutein monograph →
Herb & supplement monograph

Resveratrol

Interacts with 822 drugs

Resveratrol is a plant compound found in red grapes, berries, and peanuts that is popular for heart health, anti-aging, and antioxidant support. While lab and animal studies are promising, s...

Read the full Resveratrol monograph →
Sources

Sources & How We Checked

Cleanse'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 527 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

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

See these in context on the Vitamin B6 monograph →

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.
  13. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed
  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 →

Alpha-lipoic Acid 48 references
  1. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  2. Anon. Alpha-lipoic acid. Altern Med Rev 1998;3:308-10.
  3. Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with Type 2 diabetes. Diabetes Care 1999;22:280-7. PubMed
  4. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid: A 3-week, multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995;38:1425-33.
  5. Gleiter CH, Schreeb KH, Freudenthaler S, et al. Lack of interaction between thioctic acid, glibenclamide and acarbose. Br J Clin Pharmacol 1999;48:819-25. PubMed
  6. Jacob S, Henriksen EJ, Tritschler HJ, et al. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabet 1996;104:284-8. PubMed
  7. Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45:872-4.
  8. Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled, pilot trial. Free Rad Biol Med 1999;27:309-14.
  9. Segermann J, Hotze A, Ulrich H, Rao GS. Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels. Arzneimittelforschung 1991;41:1294-8.
  10. Beitner H. Randomized, placebo controlled, double-blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoaging of facial skin. Br J Dermatol 2003;149:841-9.
  11. Ziegler D, Nowak H, Kempler P, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A meta-analysis. Diabet Med 2004;21:114-21.
  12. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  13. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  14. Vincent HK, Bourguignon CM, Vincent KR, Taylor AG. Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. J Alt Complement Med 2007;13:577-84. PubMed
  15. Furukawa N, Miyamura N, Nishida K, et al. Possible relevance of alpha lipoic acid contained in a health supplement in a case of insulin autoimmune syndrome. Diabetes Res Clin Pract 2007;75:366-7. PubMed
  16. Ziegler D., Ametov A., Barinov A., Dyck P. J., Gurieva I., Low P. A., Munzel U., Yakhno N., Raz I., Novosadova M., Maus J., Samigullin, R. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Car
  17. Gu X. M., Zhang S. S., Wu J. C., Tang Z. Y., Lu Z. Q., Li H., Liu C., Chen L., Ning, G. [Efficacy and safety of high-dose a-lipoic acid in the treatment of diabetic polyneuropathy]. Zhonghua Yi Xue Za Zhi 2010;90(35):2473-2476.
  18. Porasuphatana S., Suddee S., Nartnampong A., Konsil J., Harnwong B., Santaweesuk A. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled
  19. Ansar H., Mazloom Z., Kazemi F., Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J 2011;32(6):584-588. DOI
  20. de Oliveira A. M., Rondó P. H., Luzia L. A., D'Abronzo F. H., Illison V. K. The effects of lipoic acid and a-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, pla
  21. Mazloom Z., Ansar H. The Effect of Alpha-Lipoic Acid on Blood Pressure in Type 2 Diabetics. Iranian Journal of Endocrinology and Metabolism 2009;11(3):245-250.
  22. Volchegorskii I. A., Rassokhina L. M., Koliadich M. I., Alekseev M. I. [Comparative study of alpha-lipoic acid and mexidol effects on affective status, cognitive functions and quality of life in diabetes mellitus patients]. Eksp Klin Farmakol 2011;74(11):
  23. Cavalcanti D. R., da Silveira F. R. Alpha lipoic acid in burning mouth syndrome--a randomized double-blind placebo-controlled trial. J Oral Pathol Med 2009;38(3):254-261. PubMed
  24. Koh E. H., Lee W. J., Lee S. A., Kim E. H., Cho E. H., Jeong E., Kim D. W., Kim M. S., Park J. Y., Park K. G., Lee H. J., Lee I. K., Lim S., Jang H. C., Lee K. H., Lee K. U. Effects of alpha-lipoic Acid on body weight in obese subjects. Am J Med 2011;124( PubMed
  25. Bergqvist-Karlsson, A., Thelin, I., and Bergendorff, O. Contact dermatitis to alpha-lipoic acid in an anti-wrinkle cream. Contact Dermatitis 2006;55(1):56-57.
  26. Tang, J., Wingerchuk, D. M., Crum, B. A., Rubin, D. I., and Demaerschalk, B. M. Alpha-lipoic acid may improve symptomatic diabetic polyneuropathy. Neurologist. 2007;13(3):164-167. PubMed
  27. Hegazy SK, Tolba OA, Mostafa TM, Eid MA, El-Afify DR. Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes. Rev Diabet Stud 2013;10(1):58-67. PubMed
  28. Huang Z, Wan X, Liu J, et al. Short-term continuous subcutaneous insulin infusion combined with insulin sensitizers rosiglitazone, metformin, or antioxidant a-lipoic acid in patients with newly diagnosed type 2 diabetes mellitus. Diabetes Technol Ther 201
  29. Sarezky D, Raquib AR, Dunaief JL, Kim BJ. Tolerability in the elderly population of high-dose alpha lipoic acid: a potential antioxidant therapy for the eye. Clin Ophthalmol. 2016 Sep 29;10:1899-1903. PubMed
  30. Boriani F, Granchi D, Roatti G, Merlini L, Sabattini T, Baldini N. Alpha-lipoic acid after median nerve decompression at the carpal tunnel: a randomized controlled trial. J Hand Surg Am. 2017 Apr;42(4):236-42. PubMed
  31. Karkabounas S, Papadopoulos N, Anastasiadou C, et al. Effects of a-lipoic Acid, carnosine, and thiamine supplementation in obese patients with type 2 diabetes mellitus: A randomized, double-blind study. J Med Food. 2018;21(12):1197-1203.
  32. Murray GL, Colombo J. (r)Alpha lipoic acid is a safe, effective pharmacologic therapy of chronic orthostatic hypotension associated with low sympathetic tone. Int J Angiol. 2019;28(3):188-193. PubMed
  33. Bobe G, Michels AJ, Zhang WJ, et al. A randomized controlled trial of long-term (R)-α-lipoic acid supplementation promotes weight loss in overweight or obese adults without altering baseline elevated plasma triglyceride concentrations. J Nutr. 2020:
  34. Passiatore M, Perna A, De-Vitis R, Taccardo G. The use of alfa-lipoic acid-R (ALA-R) in patients with mild-moderate carpal tunnel syndrome: A randomised controlled open label prospective study. Malays Orthop J. 2020;14(1):1-6. PubMed
  35. El-Nahas MR, Elkannishy G, Abdelhafez H, Elkhamisy ET, El-Sehrawy AA. Oral alpha lipoic acid treatment for symptomatic diabetic peripheral neuropathy: A randomized double-blinded placebo-controlled study. Endocr Metab Immune Disord Drug Targets. 2020. PubMed
  36. Kim BJ, Hunter A, Brucker AJ, et al. Orally administered alpha lipoic acid as a treatment for geographic atrophy: A randomized clinical trial. Ophthalmol Retina. 2020;4(9):889-898. PubMed
  37. Derosa G, D'Angelo A, Preti P, Maffioli P. Safety and efficacy of alpha lipoic acid during 4 years of observation: A retrospective, clinical trial in healthy subjects in primary prevention. Drug Des Devel Ther. 2020;14:5367-5374.
  38. Sun Y, Guan X, Wang H, et al. Randomized clinical trial of combined therapy with oral a-lipoic acid and NB-UVB for nonsegmental stable vitiligo. Dermatol Ther. 2021;34(1):e14610.
  39. Gilron I, Robb S, Tu D, et al. Double-blind, randomized, placebo-controlled crossover trial of alpha-lipoic acid for the treatment of fibromyalgia pain: the IMPALA trial. Pain. 2021;162(2):561-568. PubMed
  40. Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R. Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking a-lipoic acid. Clin Endocrinol (Oxf). 2014;81(2):204-9.
  41. Yukina M, Nuralieva N, Solovyev M, Troshina E, Vasilyev E. Insulin autoimmune syndrome. Endocrinol Diabetes Metab Case Rep. 2020;2020:19-0159. PubMed
  42. Moffa S, Improta I, Rocchetti S, Mezza T, Giaccari A. Potential cause-effect relationship between insulin autoimmune syndrome and alpha lipoic acid: Two case reports. Nutrition. 2019;57:1-4. PubMed
  43. Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking a-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313X18819601.
  44. EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, et al. Scientific opinion on the relationship between intake of alpha-lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome. EFSA J 2021;19(6):e06577. PubMed
  45. Jibril AT, Jayedi A, Shab-Bidar S. Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose-response meta-analysis of randomized trials. Endocr Connect 2022;11(10):e220322. PubMed
  46. Corazza M, Arlotti E, Schettini N, Pacetti L, Bianchi A, Borghi A. Allergic contact dermatitis due to a-lipoic acid in a topical over-the-counter product: A case report. Contact Dermatitis 2023.
  47. Velasco-Amador JP, Prados-Carmona Á, Navarro-Triviño FJ. Contact urticaria syndrome caused by alpha-lipoic acid in a master formula for vulvar lichen sclerosus. Contact Dermatitis 2023;89(2):136-137. PubMed
  48. Sehgal T, Ohri U, Mittal N, Attri P, Dishant F. A Case of Insulin Autoimmune Syndrome in an Indian Male Taking Alpha-Lipoic Acid. Cureus 2023;15(8):e43743. PubMed

See these in context on the Alpha-lipoic Acid monograph →

Riboflavin 5 references
  1. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-70. PubMed
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Leeson LJ, Weidenheimer JF. Stability of tetracycline and riboflavin. J Pharm Sci. 1969;58(3):355-7. PubMed
  4. MacLennan, S. C., Wade, F. M., Forrest, K. M., Ratanayake, P. D., Fagan, E., and Antony, J. High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. J Child Neurol. 2008;23(11):1300-1304.
  5. Dietary reference intakes (DRIs): estimated average requirements. Food and Nutrition Board, Institute of Medicine, National Academics. https://www.nal.usda.gov/sites/default/files/fnic_uploads//recommended_intakes_individuals.pdf Accessed July 24, 2017.

See these in context on the Riboflavin monograph →

Thiamine 7 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. 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
  4. Rogovik, A. L., Vohra, S., and Goldman, R. D. Safety considerations and potential interactions of vitamins: should vitamins be considered drugs? Ann.Pharmacother. 2010;44(2):311-324. PubMed
  5. Arruti N, Bernedo N, Audicana MT, Villarreal O, Uriel O, Muñoz D. Systemic allergic dermatitis caused by thiamine after iontophoresis. Contact Dermatitis. 2013 Dec;69(6):375-6. PubMed
  6. Thiamine hydrochloride injection package insert. Lake Zurich, IL: Fresenius Kabi, LLC; September 2019.
  7. Vora B, Wen A, Yee SW, et al. The Effect of Trimethoprim on Thiamine Absorption: A Transporter-Mediated Drug-Nutrient Interaction. Clin Pharmacol Ther 2023;114(2):381-392.

See these in context on the Thiamine monograph →

Pantothenic Acid 11 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Debourdeau PM, Djezzar S, Estival JL, et al. Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H. Ann Pharmacother 2001;35:424-6. DOI
  4. Schmuth, M., Wimmer, M. A., Hofer, S., Sztankay, A., Weinlich, G., Linder, D. M., Elias, P. M., Fritsch, P. O., and Fritsch, E. Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double-blind study. Br.J.Dermatol. 2 PubMed
  5. Schreck, U., Paulsen, F., Bamberg, M., and Budach, W. Intraindividual comparison of two different skin care conceptions in patients undergoing radiotherapy of the head-and-neck region. Creme or powder? Strahlenther.Onkol. 2002;178(6):321-329. PubMed
  6. Herbst, R. A., Uter, W., Pirker, C., Geier, J., and Frosch, P. J. Allergic and non-allergic periorbital dermatitis: patch test results of the Information Network of the Departments of Dermatology during a 5-year period. Contact Dermatitis 2004;51(1):13-1 PubMed
  7. Champault, G. and Patel, J. C. [Treatment of constipation with Bepanthene]. Med.Chir Dig. 1977;6(1):57-59.
  8. Scott LN, Fiume M, Bergfeld WF, et al. Safety Assessment of Panthenol, Pantothenic Acid, and Derivatives as Used in Cosmetics. Int J Toxicol 2022;41(3_suppl):77-128. PubMed
  9. Han J, Warshaw EM. Allergic Contact Dermatitis to Panthenol in "Hypoallergenic" Products. Dermatitis 2023;34(1):62-63. PubMed
  10. Blanchard G, Kerre S, Walker A, et al. Allergic contact dermatitis from pantolactone and dexpanthenol in wound healing creams. Contact Dermatitis 2022;87(5):468-471. PubMed
  11. Peltier E, Trapp S, de Salvo R, et al. A new dexpanthenol-containing liquid cleanser for atopic-prone skin: Results from two prospective clinical studies evaluating cutaneous tolerability, moisturization potential, and effects on barrier function. J Cosme PubMed

See these in context on the Pantothenic Acid monograph →

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

See these in context on the L-carnitine monograph →

Dong Quai 19 references
  1. Hirata JD, Swiersz LM, Zell B, et al. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 1997;68:981-6. PubMed
  2. Page RL II, Lawrence JD. Potentiation of warfarin by dong quai. Pharmacotherapy 1999;19:870-6. PubMed
  3. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7. DOI
  4. Eagon PK, Elm MS, Hunter DS, et al. Medicinal herbs: modulation of estrogen action. Era of Hope Mtg, Dept Defense; Breast Cancer Res Prog, Atlanta, GA 2000;Jun 8-11.
  5. Dr. Duke's Phytochemical and Ethnobotanical Databases. Available at: http://www.ars-grin.gov/duke/.
  6. Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause 2002;9:145-50. PubMed
  7. Shi M, Chang L, He G. [Stimulating action of Carthamus tinctorius L., Angelica sinensis (Oliv.) Diels and Leonurus sibiricus L. on the uterus]. Zhongguo Zhong Yao Za Zhi 1995;20:173-5, 192.
  8. Hoult JR, Paya M. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol 1996;27:713-22.. PubMed
  9. Cheong JL, Bucknall R. Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient. Postgrad Med J 2005;81:266-7.. PubMed
  10. Chang CJ, Chiu JH, Tseng LM, et al. Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells. Eur J Clin Invest 2006;36:588-96. PubMed
  11. Chuang CH, Doyle P, Wang JD, et al. Herbal medicines used during the first trimester and major congenital malformations: an analysis of data from a pregnancy cohort study. Drug Saf 2006;29:537-48. PubMed
  12. Lau CBS, Ho TCY, Chan TWL, Kim SCF. Use of dong quai (Angelica sinensis) to treat peri- and postmenopausal symptoms in women with breast cancer: is it appropriate? Menopause 2005;12:734-40.
  13. Ellis GR, Stephens MR. Untitled (photograph and a brief case report). BMJ 1999;319:650.
  14. Nambiar, S., Schwartz, R. H., and Constantino, A. Hypertension in mother and baby linked to ingestion of Chinese herbal medicine. West J Med 1999;171(3):152.
  15. Lee, S. K., Cho, H. K., Cho, S. H., Kim, S. S., Nahm, D. H., and Park, H. S. Occupational asthma and rhinitis caused by multiple herbal agents in a pharmacist. Ann.Allergy Asthma Immunol. 2001;86(4):469-474. PubMed
  16. Xu, J. and Li, G. [Observation on short-term effects of Angelica injection on chronic obstructive pulmonary disease patients with pulmonary hypertension]. Zhongguo Zhong Xi Yi Jie He Za Zhi 2000;20(3):187-189.
  17. Scott, G. N. and Elmer, G. W. Update on natural product--drug interactions. Am J Health Syst.Pharm 2-15-2002;59(4):339-347. PubMed
  18. Circosta, C., Pasquale, R. D., Palumbo, D. R., Samperi, S., and Occhiuto, F. Estrogenic activity of standardized extract of Angelica sinensis. Phytother.Res. 2006;20(8):665-669.
  19. Fung FY, Wong WH, Ang SK, et al. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017;32:88-96. PubMed

See these in context on the Dong Quai monograph →

Milk Thistle 69 references
  1. Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;9:105-13. PubMed
  2. Anon. Milk thistle: Effects on liver disease and cirrhosis and clinical adverse effects. Summary, Evidence Report/Technology Assessment: Number 21, September 2000. Agency for Healthcare Research and Quality, Rockville, MD. Available at: http://www.ahrq.g
  3. Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, et al. Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 2000;86:250-6. PubMed
  4. Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3. DOI
  5. Kim DH, Jin YH, Park JB, Kobashi K. Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull 1994;17:443-5. PubMed
  6. Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998;28:615-21. PubMed
  7. Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002;22:551-6. PubMed
  8. Boerth J, Strong KM. The clinical utility of milk thistle (Silybum marianum) in cirrhosis of the liver. J Herb Pharmacother 2002;2:11-7.
  9. Tanamly MD, Tadros F, Labeeb S, et al. Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis 2004;36:752-9. PubMed
  10. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004;76:428-40. .
  11. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006;20;1036-9.
  12. Deng JW, Shon JH, Shin HJ, et al. Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharm Res 2008;25:1807-14. PubMed
  13. Kim CS, Choi SJ, Park CY, et al. Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats. Anticancer Res 2010;30:79-85.
  14. Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94. PubMed
  15. van Erp NP, Baker SD, Zhao M, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 2005;11:7800-6.
  16. Budzinski JW, Trudeau VL, Drouin CE, et al. Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol 2007;85:966-78.
  17. Doehmer J, Weiss G, McGregor GP, Appel K. Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro 2011;25:21-7. PubMed
  18. Jiao Z, Shi XJ, Li ZD, et al. Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients. Br.J.Clin.Pharmacol. 2009;68(1):47-60.
  19. Gurley, B. J., Barone, G. W., Williams, D. K., Carrier, J., Breen, P., Yates, C. R., Song, P. F., Hubbard, M. A., Tong, Y., and Cheboyina, S. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin phar
  20. Allain, H., Schuck, S., Lebreton, S., Strenge-Hesse, A., Braun, W., Gandon, J. M., and Brissot, P. Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease. Dement.Geriatr.Cogn Disord. 1999;10(3):181-185. PubMed
  21. Angulo, P., Patel, T., Jorgensen, R. A., Therneau, T. M., and Lindor, K. D. Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 2000;32(5):897-900. PubMed
  22. Bean, P. The use of alternative medicine in the treatment of hepatitis C. Am.Clin.Lab 2002;21(4):19-21.
  23. Hussain, S. A. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J.Med.Food 2007;10(3):543-547. PubMed
  24. El-Kamary, S. S., Shardell, M. D., Abdel-Hamid, M., Ismail, S., El-Ateek, M., Metwally, M., Mikhail, N., Hashem, M., Mousa, A., Aboul-Fotouh, A., El-Kassas, M., Esmat, G., and Strickland, G. T. A randomized controlled trial to assess the safety and effic
  25. Gharagozloo, M., Moayedi, B., Zakerinia, M., Hamidi, M., Karimi, M., Maracy, M., and Amirghofran, Z. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. Fundam.Clin.Pharmaco
  26. Ladas, E. J., Kroll, D. J., Oberlies, N. H., Cheng, B., Ndao, D. H., Rheingold, S. R., and Kelly, K. M. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL PubMed
  27. Sayyah, M., Boostani, H., Pakseresht, S., and Malayeri, A. Comparison of Silybum marianum (L.) Gaertn. with fluoxetine in the treatment of Obsessive-Compulsive Disorder. Prog.Neuropsychopharmacol.Biol.Psychiatry 3-17-2010;34(2):362-365. PubMed
  28. Flaig, T. W., Glode, M., Gustafson, D., van, Bokhoven A., Tao, Y., Wilson, S., Su, L. J., Li, Y., Harrison, G., Agarwal, R., Crawford, E. D., Lucia, M. S., and Pollak, M. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients w
  29. Ramirez-Santos, A., Perez-Bustillo, A., Gonzalez-Sixto, B., Suarez-Amor, O., and Rodriguez-Prieto, M. A. [Acute generalized exanthematous pustulosis due to milk thistle (Silybum marianum) tea]. Actas Dermosifiliogr. 2011;102(9):744-745. DOI
  30. Loguercio C, Andreone P, Brisc C, et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic Biol Med 2012;52(9):1658-65. PubMed
  31. Yakoot, M. and Salem, A. Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial. BMC.Gastroenterol. 2012;12:32. PubMed
  32. Fallahzadeh, M. K., Dormanesh, B., Sagheb, M. M., Roozbeh, J., Vessal, G., Pakfetrat, M., Daneshbod, Y., Kamali-Sarvestani, E., and Lankarani, K. B. Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic
  33. Fried, M. W., Navarro, V. J., Afdhal, N., Belle, S. H., Wahed, A. S., Hawke, R. L., Doo, E., Meyers, C. M., and Reddy, K. R. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon t
  34. Fallah Huseini, H., Larijani, B., Fakhrzadeh, H., Rajabi Pour, B., Akhondzadeh, S., Toliat, T., and Heshmat, R. The clinical trial of Silybum Marianum seed extract (Silymarin) on type II diabetic patients with hyperlipidemia. Iran J.Diabetes Lipid Disord
  35. Mironets VI, Krasovskaia EA, and Polishchuk II. [A case of urticaria during Carsil treatment]. Vrach Delo 1990;7:86-87.
  36. Velussi M, Cernigoi AM, Viezzoli L, and et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Curr Ther Res 1993;53(5):533-545. DOI
  37. Marcelli R, Bizzoni P, Conte D, and et al. Randomized controlled study of the efficacy and tolerability of a short course of IdB 1016 in the treatment of chronic persistent hepatitis. Eur Bull Drug Res 1992;1(3):131-135.
  38. Vailati A, Aristia L, Sozze E, and et al. Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 1993;64(3):219-228.
  39. Marena C and Lampertico M. Preliminary clinical development of silipide: a new complex of silybin in toxic liver disorders. Planta Med 1991;57(2):A124-A125. DOI
  40. Grungreiff K, Albrecht M, and Strenge-Hesse A. Benefit of medicinal liver therapy in general practice. Med Welt 1995;46:222-227.
  41. Frerick F, Kuhn U, and Strenge-Hesse A. Silymarin--ein Phytopharmakon zur Behandlung toxischen Leberschaden: Anwendungsbeobachtung bei 2169 Patienten. Kassenarzt 1990;33:36-41.
  42. Schuppan D, Strosser W, Burkard G, and et al. Influence of Legalon(TM) 140 on the metabolism of collagen in patients with chronic liver disease--Review by measurement of PIIINP-values. Zeitschrift fur Allgemeinmedizin 1998;74:577-584.
  43. Studlar M. Die Behandlung chronischer Leberkrankungen mit Silymarin und B-Vitaminen. Therapiewoche 1985;35:3375-3378.
  44. Anon. Adverse reaction: milk thistle-associated toxicity. Nurse Drug Alert 1999;23(7):51.
  45. Gufford BT, Chen G, Vergara AG, et al. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction. Drug Metab Dispos. 2015;43(9):1353-9. PubMed
  46. El-Shitany NA, Hegazy S, El-Desoky K. Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine. 2010;17(2):116-25. PubMed
  47. Seidlová-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W. Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx
  48. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  49. Derosa G, Romano D, D'Angelo A, Maffioli P. Berberis aristata/Silybum marianum fixed combination (Berberol(®)) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial. Phyto PubMed
  50. Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015;15:334. PubMed
  51. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-6. PubMed
  52. Rastegarpanah M, Malekzadeh R, Vahedi H, et al. A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis. Chin J Integr Med. 2015;21(12):902-6. PubMed
  53. Di Pierro F, Bellone I, Rapacioli G, Putignano P. Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins. Diabetes Metab Syndr Obes. 2015;8:8 PubMed
  54. Di Pierro F, Villanova N, Agostini F, Marzocchi R, Soverini V, Marchesini G. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control. Diabetes Metab Syndr Obes. 2012;5:213-7. PubMed
  55. Guarino G, Strollo F, Carbone L, et al. Bioimpedance analysis, metabolic effects and safety of the association Berberis aristata/Bilybum marianum: a 52-week double-blind, placebo-controlled study in obese patients with type 2 diabetes. J Biol Regul Homeos
  56. Ebrahimpour-Koujan S, Gargari BP, Mobasseri M, Valizadeh H, Asghari-Jafarabadi M. Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A T
  57. Lash DB, Ward S. CYP2C9-mediated warfarin and milk thistle interaction. J Clin Pharm Ther. 2019. PubMed
  58. Malekshah RE, Khaleghian A. Influence of Silybum marianum on morphine addicted rats, biochemical parameters and molecular simulation studies on µ-opioid receptor. Drug Res (Stuttg). 2019;69(11):630-638. PubMed
  59. Soleymani S, Ayati MH, Mansourzadeh MJ, Namazi N, Zargaran A. The effects of Silymarin on the features of cardiometabolic syndrome in adults: A systematic review and meta-analysis. Phytother Res. 2022 Jan 11. doi: 10.1002/ptr.7364. PubMed
  60. Gamissans M, Expósito-Serrano V, López-Llunell C, Valdivieso L, Garbayo-Salmons P. Bullous pemphigoid triggered by Silybum marianum: an unexpected side effect of an herbal remedy. Int J Dermatol. 2021 Aug 7. doi: 10.1111/ijd.15822. PubMed
  61. Aboras SI, Korany MA, El-Yazbi AF, Ragab MAA, Abdine HH. In-depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 and ledipasvir in rat plasma using LC-MS. Biomed Chromatogr 2022;36(9):e5427. PubMed
  62. Wattanakrai P, Nimmannitya K. A Randomized, Double-Blind, Split-Face Study of Topical Silymarin vs 2% Hydroquinone Cream in Melasmas. J Drugs Dermatol 2022;21(12):1304-1310. PubMed
  63. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
  64. Zhang W, Zhang Y, Wen C, Jiang X, Wang L. In vitro Assessment of the Effects of Silybin on CYP2B6-mediated Metabolism. Planta Med 2023. PubMed
  65. Bechtold BJ, Lynch KD, Oyanna VO, et al. Rifampin- and Silymarin-Mediated Pharmacokinetic Interactions of Exogenous and Endogenous Substrates in a Transgenic OATP1B Mouse Model. Mol Pharm 2024;21(5):2284-2297. PubMed
  66. Mohammadi S, Asbaghi O, Afrisham R, et al. Impacts of Supplementation with Silymarin on Cardiovascular Risk Factors: A Systematic Review and Dose-Response Meta-Analysis. Antioxidants (Basel) 2024;13(4):390. PubMed
  67. Rustamzadeh A, Sadigh N, Vahabi Z, et al. Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer's patients: A double-blind placebo-controlled randomized clinical trial. IBRO Neurosci Rep 2024;17:108-121. PubMed
  68. Fatemi Shandiz A, Karimi G, Dayyani M, Hosseini S, Elyasi S. Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer. J Oncol Pharm Pract 2024. PubMed
  69. Duan X, Bai W, Hu J, et al. Inhibitory effect of flavonoids on multidrug and toxin extrusion protein 1 function: Implications for food/herb-drug interaction and drug-induced kidney injury. J Appl Toxicol 2024;44(9):1388-1402. PubMed

See these in context on the Milk Thistle monograph →

Cranberry 33 references
  1. Anon. Possible interaction between warfarin and cranberry juice. Current Problems in Pharmacovigilance 2003;29:8. PubMed
  2. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33. PubMed
  3. Hodek P, Trefil P, Stiborova M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 2002;139:1-21.. PubMed
  4. Grant P. Warfarin and cranberry juice: An interaction? J Heart Valve Dis 2004;13:25-6.
  5. Suvarna R, Pirmohamed M, Henderson L. Possible interaction between warfarin and cranberry juice. BMJ 2003;327:1454. PubMed
  6. Li Z, Seeram NP, Carpenter CL, et al. Cranberry does not affect prothrombin time in male subjects on warfarin. J Am Diet Assoc 2006;106:2057-61. PubMed
  7. Lilja JJ, Backman JT, Neuvonen PJ. Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam - probes of CYP2C9, CYP1A2 and CYP3A4. Clin Pharmacol The 2007:81:833-9. PubMed
  8. Wing DA, Rumney PJ, Preslicka CW, Chung JH. Daily cranberry juice for the prevention of asymptomatic bacteriuria in pregnancy: a randomized, controlled pilot study. J Urol 2008;180:1367-72. PubMed
  9. Mohammed Abdul MI, Jiang X, Williams KM, et al. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. Br J Pharmacol 2008;154:1691-700. PubMed
  10. McMurdo MET, Argo I, Phillips G, et al. Cranberry or trimethoprim for the prevention of recurrently urinary tract infections? A randomized controlled trial in older women. J Antimicrob Chemother 2009;63:389-95.
  11. Mergenhagen KA, Sherman O. Elevated International Normalized Ratio after concurrent ingestion of cranberry sauce and warfarin. Am J Health-Syst Pharm 2008;65:2113-6. PubMed
  12. Ansell J, McDonough M, Zhao Y, et al. The absence of an interaction between warfarin and cranberry juice: a randomized, double-blind trial. J Clin Pharmacol 2009;49:824-30. PubMed
  13. Haber SL, Cauthon KA, Raney EC. Cranberry and warfarin interaction: a case report and review of the literature. Consult Pharm 2012;27:58-65. PubMed
  14. Hamann GL, Campbell JD, George CM. Warfarin-cranberry juice interaction. Ann Pharmacother 2011;45:e17. PubMed
  15. Roberts D, Flanagan P. Case report: Cranberry juice and warfarin. Home Healthc Nurse 2011;29:92-7.
  16. Garcia-Calatayud, S., Larreina Cordoba, J. J., and Lozano De La Torre MJ. [Severe cranberry juice poisoning]. An.Esp.Pediatr. 2002;56(1):72-73.
  17. Patel, D. A., Gillespie, B., Sobel, J. D., Leaman, D., Nyirjesy, P., Weitz, M. V., and Foxman, B. Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study. Am J Obstet.Gy PubMed
  18. Isele, H. [Fatal bleeding under warfarin plus cranberry juice. Is it due to salicylic acid?]. MMW.Fortschr.Med 3-11-2004;146(11):13.
  19. Linsenmeyer, T. A., Harrison, B., Oakley, A., Kirshblum, S., Stock, J. A., and Millis, S. R. Evaluation of cranberry supplement for reduction of urinary tract infections in individuals with neurogenic bladders secondary to spinal cord injury. A prospecti
  20. McMurdo, M. E., Bissett, L. Y., Price, R. J., Phillips, G., and Crombie, I. K. Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial. Age Ageing 2005;34(3):256- PubMed
  21. Sylvan, L. and Justice, N. P. Possible interaction between warfarin and cranberry juice. Am Fam.Physician 9-15-2005;72(6):1000.
  22. Niklasson, A. and Andren, L. [Interaction between Waran and cranberry juice]. Lakartidningen 3-15-2006;103(11):853-854.
  23. Rindone, J. P. and Murphy, T. W. Warfarin-cranberry juice interaction resulting in profound hypoprothrombinemia and bleeding. Am J Ther 2006;13(3):283-284. PubMed
  24. Uesawa, Y. and Mohri, K. Effects of cranberry juice on nifedipine pharmacokinetics in rats. J Pharm Pharmacol 2006;58(8):1067-1072. PubMed
  25. Valentova, K., Stejskal, D., Bednar, P., Vostalova, J., Cihalik, C., Vecerova, R., Koukalova, D., Kolar, M., Reichenbach, R., Sknouril, L., Ulrichova, J., and Simanek, V. Biosafety, antioxidant status, and metabolites in urine after consumption of dried
  26. Royer, D. J., George, J. N., and Terrell, D. R. Thrombocytopenia as an adverse effect of complementary and alternative medicines, herbal remedies, nutritional supplements, foods, and beverages. Eur J Haematol 2010;84(5):421-429. PubMed
  27. Stapleton, A. E., Dziura, J., Hooton, T. M., Cox, M. E., Yarova-Yarovaya, Y., Chen, S., and Gupta, K. Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily: a randomized controlled trial. Mayo.Clin.Proc. PubMed
  28. Doad GJ, Kabange W. Cranberry juice, atorvastatin and back pain. J Med Assoc Ga 2014;103(1):14.
  29. Griffiths AP, Beddall A, Pegler S. Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin. J R Soc Promot Health 2008;128(6):324-6. PubMed
  30. Mellen CK, Ford M, Rindone JP. Effect of high-dose cranberry juice on the pharmacodynamics of warfarin in patients. Br J Clin Pharmacol 2010;70(1):139-42. PubMed
  31. Ushijima K, Tsuruoka S, Tsuda H, Hasegawa G, Obi Y, Kaneda T, Takahashi M, Maekawa T, Sasaki T, Koshimizu TA, Fujimura A. Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects. Br J Clin Pharmaco PubMed
  32. Ngo N, Brantley SJ, Carrizosa DR, et al. The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation. J Exp Pharmacol. 2010;2010(2):83-91.
  33. Williams G, Stothart CI, Hahn D, Stephens JH, Craig JC, Hodson EM. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2023;11(11):CD001321. PubMed

See these in context on the Cranberry monograph →

Selenium 36 references
  1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  2. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  3. Trafikowska U, Zachara BA, Wiacek M, et al. Selenium supply and glutathione peroxidase activity in breastfed Polish infants. Acta Paediatr 1996;85:1143-5. PubMed
  4. Duffield-Lillico AJ, Slate EH, Reid ME, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 2003;95:1477-81.. PubMed
  5. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  6. Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96. PubMed
  7. Davila JC, Edds GT, Osuna O, Simpson CF. Modification of the effects of aflatoxin B1 and warfarin in young pigs given selenium. Am J Vet Res 1983;44:1877-83. DOI
  8. Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in healthy nulliparas. S Afr Med J 1988;73:163-5.
  9. Lloyd B, Lloyd RS, Clayton BE. Effect of smoking, alcohol and other factors on the selenium status of a healthy population. J Epidemiol Commun Health 1983;37:213-7. PubMed
  10. Capel ID, Jenner M, Williams DC, et al. The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity. J Steroid Biochem 1981;14:729-32. PubMed
  11. Contempre B, Dumont JE, Ngo B, et al. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol PubMed
  12. Hofbauer LC, Spitzweg C, Magerstadt RA, Heufelder AE. Selenium-induced thyroid dysfunction. Postgrad Med J 1997;73:103-4. PubMed
  13. Debski B, Milner JA. Dietary selenium supplementation prolongs pentobarbital induced hypnosis. J Nutr Biochem 2004;15:548-53. PubMed
  14. Ishikawa M, Sasaki M, Koiwai K, et al. Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. J Pharmacobiodyn 1992;15:377-85. PubMed
  15. Lippmann SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial (SELECT). JAMA 2009;301:39-51. DOI
  16. Reid SM, Middleton P, Cossich MC, Crowther CA. Interventions for clinical and subclinical hypothyroidism in pregnancy. Cochrane Database Syst Rev 2010;(7):CD007752. PubMed
  17. Vinceti, M., Wei, E. T., Malagoli, C., Bergomi, M., and Vivoli, G. Adverse health effects of selenium in humans. Rev.Environ.Health 2001;16(4):233-251. PubMed
  18. Abrams, C. K., Siram, S. M., Galsim, C., Johnson-Hamilton, H., Munford, F. L., and Mezghebe, H. Selenium deficiency in long-term total parenteral nutrition. Nutr Clin Pract 1992;7(4):175-178. PubMed
  19. Spiller, H. A. and Pfiefer, E. Two fatal cases of selenium toxicity. Forensic Sci Int 8-24-2007;171(1):67-72. PubMed
  20. Negro, R., Greco, G., Mangieri, T., Pezzarossa, A., Dazzi, D., and Hassan, H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol.Metab 2007;92(4):1263-1268. PubMed
  21. Alexander, J. Selenium. Novartis.Found.Symp 2007;282:143-149.
  22. Salonen, J. T., Salonen, R., Seppanen, K., Rinta-Kiikka, S., Kuukka, M., Korpela, H., Alfthan, G., Kantola, M., and Schalch, W. Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial
  23. Kupka, R., Mugusi, F., Aboud, S., Msamanga, G. I., Finkelstein, J. L., Spiegelman, D., and Fawzi, W. W. Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and chil
  24. Kamble, P., Mohsin, N., Jha, A., Date, A., Upadhaya, A., Mohammad, E., Khalil, M., Pakkyara, A., and Budruddin, M. Selenium intoxication with selenite broth resulting in acute renal failure and severe gastritis. Saudi.J Kidney Dis.Transpl. 2009;20(1):106
  25. Peretz, A., Neve, J., Desmedt, J., Duchateau, J., Dramaix, M., and Famaey, J. P. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am.J Clin.Nutr. 1991;53(5):1323-1328. PubMed
  26. Kumpulainen, J., Salmenpera, L., Siimes, M. A., Koivistoinen, P., and Perheentupa, J. Selenium status of exclusively breast-fed infants as influenced by maternal organic or inorganic selenium supplementation. Am.J Clin.Nutr. 1985;42(5):829-835. PubMed
  27. Han, L. and Zhou, S. M. Selenium supplement in the prevention of pregnancy induced hypertension. Chin Med J (Engl) 1994;107(11):870-871.
  28. Kiremidjian-Schumacher, L., Roy, M., Wishe, H. I., Cohen, M. W., and Stotzky, G. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol.Trace Elem.Res. 1994;41(1-2):115-127. PubMed
  29. Srivastava, A. K., Gupta, B. N., Bihari, V., and Gaur, J. S. Generalized hair loss and selenium exposure. Vet.Hum.Toxicol. 1995;37(5):468-469.
  30. Sudfeld CR, Aboud S, Kupka R, et al. Effect of selenium supplementation on HIV-1 RNA detection in breast milk of Tanzanian women. Nutrition 2014;30(9):1081-4. PubMed
  31. Rees K, Hartley L, Day C, et al. Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;1:CD009671. PubMed
  32. Thompson PA, Ashbeck EL, Roe DJ, et al. Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes. J Natl Cancer Inst. 2016;108(12). PubMed
  33. Wichman J, Winther KH, Bonnema SJ, Hegedüs L. Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: a systematic review and meta-analysis. Thyroid 2016;26(12):1681-92. PubMed
  34. Vinceti M, Filippini T, Rothman KJ. Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis. Eur J Epidemiol. 2018 Sep;33(9):789-810. Epub 2018 Jul 5. Review. PubMed
  35. Fallah S, Sani FV, Firoozrai M. Effect of contraceptive pill on the selenium and zinc status of healthy subjects. Contraception. 2009;80(1):40-3. PubMed
  36. Malpas CB, Vivash L, Genc S, et al. A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate Alzheimer's Disease. J Alzheimers Dis. 2016;54(1):223-232. PubMed

See these in context on the Selenium monograph →

Dandelion 27 references
  1. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol 2001;53:1323-9. PubMed
  2. Williams CA, Goldstone F, Greenham J. Flavonoids, cinnamic acids and coumarins from the different tissues and medicinal preparations of Taraxacum officinale. Phytochemistry 1996;42:121-7. PubMed
  3. Hussain Z, Waheed A, Qureshi RA, et al. The effect of medicinal plants of Islamabad and Murree region of Pakistan on insulin secretion from INS-1 cells. Phytother Res 2004;18:73-7. PubMed
  4. Racz-Kotilla E, Racz G, Solomon A. The action of Taraxacum officinale extracts on the body weight and diuresis of laboratory animals. Planta Med 1974;26:212-7. PubMed
  5. Zhu M, Wong PY, Li RC. Effects of taraxacum mongolicum on the bioavailability and disposition of ciprofloxacin in rats. J Pharm Sci 1999;88:632-4. PubMed
  6. Jovanovic M, Mimica-Dukic N, Poljacki M, Boza P. Erythema multiforme due to contact with weeds: a recurrence after patch testing. Contact Dermatitis 2003;48:17-25. PubMed
  7. Chivato T, Juan F, Montoro A, Laguna R. Anaphylaxis induced by ingestion of a pollen compound. J Investig Allergol Clin Immunol 1996;6:208-9.
  8. Cohen SH, Yunginger JW, Rosenberg N, Fink JN. Acute allergic reaction after composite pollen ingestion. J Allergy Clin Immunol 1979;64:270-4. PubMed
  9. Lovell CR, Rowan M. Dandelion dermatitis. Contact Dermatitis 1991;25:185-8. PubMed
  10. Agarwal SC, Crook JR, Pepper CB. Herbal remedies -- how safe are they? A case report of polymorphic ventricular tachycardia/ventricular fibrillation induced by herbal medication used for obesity. Int J Cardiol 2006;106:260-1. PubMed
  11. Martín-Muñoz MF, Bartolome B, Caminoa M, et al. Bee pollen: a dangerous food for allergic children. Identification of responsible allergens. Allergol Immunopathol (Madr) 2010;38:263-5. PubMed
  12. Neef H, Cilli F, Declerck PJ, et al. Platelet anti-aggregating activity of Taraxacum officinale Weber. Phytotherapy Research 1996;10:s138-s140.
  13. Cuzzolin L, Zaffani S, and Benoni G. Safety implications regarding use of phytomedicines. Eur.J Clin Pharmacol. 2006;62:37-42. PubMed
  14. Posadzki, P., Watson, L. K., and Ernst, E. Adverse effects of herbal medicines: an overview of systematic reviews. Clin Med 2013;13(1):7-12. PubMed
  15. Wakelin, S. H., Marren, P., Young, E., and Shaw, S. Compositae sensitivity and chronic hand dermatitis in a seven-year-old boy. Br J Dermatol 1997;137(2):289-291. PubMed
  16. Ingber, A. Seasonal allergic contact dermatitis from Taraxacum officinale (dandelion) in an Israeli florist. Contact Dermatitis 2000;43(1):49.
  17. Rodriguez, B., Rodriguez, A., de Barrio, M., Tornero, P., and Baeza, M. L. Asthma induced by canary food mix. Allergy Asthma Proc. 2003;24(4):265-268.
  18. Syhaieva, I. A. [Efficiency of specific immunotherapy in treatment of patients with seasonal allergic rhinitis]. Lik.Sprava. 2006;(1-2):51-53.
  19. Catania, M. A., Oteri, A., Caiello, P., Russo, A., Salvo, F., Giustini, E. S., Caputi, A. P., and Polimeni, G. Hemorrhagic cystitis induced by an herbal mixture. South.Med.J. 2010;103(1):90-92. PubMed
  20. Goksu, E., Eken, C., Karadeniz, O., and Kucukyilmaz, O. First report of hypoglycemia secondary to dandelion (Taraxacum officinale) ingestion. Am J Emerg.Med 2010;28(1):111-112. PubMed
  21. Fernandez-Gonzalez, D., Gonzalez-Parrado, Z., Vega-Maray, A. M., Valencia-Barrera, R. M., Camazon-Izquierdo, B., De, Nuntiis P., and Mandrioli, P. Platanus pollen allergen, Pla a 1: quantification in the atmosphere and influence on a sensitizing populati
  22. Liang, K. L., Su, M. C., Shiao, J. Y., Wu, S. H., Li, Y. H., and Jiang, R. S. Role of pollen allergy in Taiwanese patients with allergic rhinitis. J Formos.Med Assoc. 2010;109(12):879-885. PubMed
  23. Yang, Y., Zhao, Y., Wang, C. S., Wang, X. D., and Zhang, L. [Prevalence of sensitization to aeroallergens in 10 030 patients with allergic rhinitis]. Zhonghua Er.Bi Yan.Hou Tou.Jing.Wai Ke Za Zhi 2011;46(11):914-920.
  24. Davies, M. G. and Kersey, P. J. Contact allergy to yarrow and dandelion. Contact Dermatitis 1986;14(4):256-257. PubMed
  25. Collins JM and Miller DR. Dandelion green bezoar following antrectomy and vagotomy - case report. J Kansas Med Soc 1966;67(6):303-304.
  26. Moriarty B, Pinney JH, Owen-Casey MP, Rustin MH, Deroide F, Laing C, Davenport A. Digital necrosis from dandelion tea. Br J Dermatol. 2013 Jul;169(1):227-30. PubMed
  27. Onal S, Timur S, Okutucu B, Zihnioglu F. Inhibition of alphaglucosidase by aqueous extracts of some potent antidiabetic medicinal herbs. Prep Biochem Biotechnol 2005;35:29-36.

See these in context on the Dandelion monograph →

Agaricus Mushroom 5 references
  1. Hsu CH, Liao YL, Lin SC, et al. The mushroom Agaricus Blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo-controlled clinical trial. J Altern Complement Med 2
  2. Mukai H, Watanabe T, Ando M, Katsumata N. An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patients. Jpn J Clin Oncol 2006;36:808-10. PubMed
  3. Ohno S, Sumiyoshi Y, Hashine K, et al. Phase I clinical study of the dietary supplement, Agaricus blazei Murill, in cancer patients in remission. Evid Based Complement Alternat Med 2011, doi 10.1155/2011/192381.
  4. Suehiro M, Katoh N, Kishimoto S. Chelitis due to Agaricus blazei Murill mushroom extract. Contact Dermatitis 2007;56(5):293-4.
  5. Iwai N, Okuda T, Sawada R, et al. Interstitial lung disease associated with Agaricus blazei Murill in a patient with pancreatic ductal adenocarcinoma receiving gemcitabine-based therapy. Case Rep Gastroenterol 2022;16(1):229-234.

See these in context on the Agaricus Mushroom monograph →

Ginger 64 references
  1. Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1991;38:19-24. PubMed
  2. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2000;(2):CD000145. PubMed
  3. Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 2001;97:577-82. DOI
  4. Backon J. Ginger in preventing nausea and vomiting of pregnancy; a caveat due to its thromboxane synthetase activity and effect on testosterone binding. Eur J Obstet Gynecol Reprod Biol 1991;42:163-4. PubMed
  5. Srivastava KC. Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids 1989;35:183-5. PubMed
  6. Stewart JJ, Wood MJ, Wood CD, Mims ME. Effects of ginger on motion sickness susceptibility and gastric function. Pharmacology 1991;42:111-20. PubMed
  7. Smith C, Crowther C, Willson K, et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639-45. PubMed
  8. Portnoi G, Chng LA, Karimi-Tabesh L, et al. Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy. Am J Obstet Gynecol 2003;189:1374-7.. PubMed
  9. Wigler I, Grotto I, Caspi D, Yaron M. The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis. Osteoarthritis Cartilage 2003;11:783-9. PubMed
  10. Ghayur MN, Gilani AH. Ginger lowers blood pressure through blockade of voltage-dependent calcium channels. J Cardiovasc Pharmacol 2005;45:74-80. PubMed
  11. Thomson M, Al-Qattan KK, Al-Sawan SM, et al. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot Essent Fatty Acids 2002;67:475-8. PubMed
  12. Kanerva L, Estlander T, Jolanki R. Occupational allergic contact dermatitis from spices. Contact Dermatitis 1996;35:157-62. PubMed
  13. Akhani SP, Vishwakarma SL, Goyal RK. Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats. J Pharm Pharmacol 2004;56:101-5.
  14. Kruth P, Brosi E, Fux R, et al. Ginger-associated overanticoagulation by phenprocoumon. Ann Pharmacother 2004;38:257-60. PubMed
  15. Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005;59:425-32. PubMed
  16. Borrelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol 2005;105:849-56. PubMed
  17. Smith C, Crowther C, Wilson K et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639-45. PubMed
  18. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8. PubMed
  19. 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.
  20. Ozgoli G, Goli M, Moattar F. Comparison of effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea. J Altern Complement Med 2009;15:129-32. PubMed
  21. Black CD, Herring MP, Hurley DJ, O'Connor PJ. Ginger (Zingiber officinale) reduces muscle pain caused by eccentric exercise. J Pain 2010;11:894-903. PubMed
  22. Heitmann K, Nordeng H, Holst L. Safety of ginger use in pregnancy: results from a large population-based cohort study. Eur J Clin Pharmacol 2012 Jun 17. PubMed
  23. Ryan JL, Heckler CE, Roscoe JA, et al. Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients. Support Care Cancer. 2012;20:1479-89. PubMed
  24. Backon J. Ginger as an antiemetic: possible side effects due to its thromboxane synthetase activity. Anaesthesia. 1991;46(8):705-6.. PubMed
  25. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002;27:391-401. PubMed
  26. Argento A, Tiraferri E, Marzaloni M. [Oral anticoagulants and medicinal plants. An emerging interaction]. Ann Ital Med Int. 2000;15:139-43.
  27. Young HY, Liao JC, Chang YS, et al. Synergistic effect of ginger and nifedipine on human platelet aggregation: a study in hypertensive patients and normal volunteers. Am J Chin Med. 2006;34:545-51. PubMed
  28. Greenway FL, Liu Z, Martin CK, et al. Safety and efficacy of NT, an herbal supplement, in treating human obesity. Int J Obes (Lond). 2006;30:1737-41. PubMed
  29. Shalansky S, Lynd L, Richardson K, et al. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27:1237-47. PubMed
  30. Lesho EP, Saullo L, Udvari-Nagy S. A 76-year-old woman with erratic anticoagulation. Cleve Clin J Med. 2004;71:651-6. PubMed
  31. Okonta JM, Uboh M, Obonga WO. Herb-Drug Interaction: A Case Study of Effect of Ginger on the Pharmacokinetic of Metronidazole in Rabbit. Indian Journal of Pharmaceutical Sciences (India) 2008;70(230):232. PubMed
  32. Chiang HM, Chao PD, Hsiu SL, et al. Ginger significantly decreased the oral bioavailability of cyclosporine in rats. Am J Chin Med. 2006;34:845-55. PubMed
  33. Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol. 2005;97:227-30. PubMed
  34. Ojewole JA. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. Phytother Res. 2006;20:764-72.
  35. Al-Amin ZM, Thomson M, Al-Qattan KK, et al. Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. Br J Nutr. 2006;96:660-6.
  36. Islam MS, Choi H. Comparative effects of dietary ginger (Zingiber officinale) and garlic (Allium sativum) investigated in a type 2 diabetes model of rats. J Med Food. 2008;11:152-9.
  37. Cady RK, Goldstein J, Nett R, et al. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache 2011;51:1078-86.
  38. Futrell, J. M. and Rietschel, R. L. Spice allergy evaluated by results of patch tests. Cutis 1993;52(5):288-290.
  39. Sripramote, M. and Lekhyananda, N. A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy. J Med Assoc.Thai. 2003;86(9):846-853.
  40. Lohsiriwat, S., Rukkiat, M., Chaikomin, R., and Leelakusolvong, S. Effect of ginger on lower esophageal sphincter pressure. J.Med.Assoc.Thai. 2010;93(3):366-372.
  41. Liu, P. H. and Ho, H. L. Ginger and drug bezoar induced small bowel obstruction. J R.Coll.Surg.Edinb. 1983;28(6):397-398.
  42. Maghbooli M, Golipour F, Moghimi Esfandabadi A, Yousefi M. Comparison between the efficacy of ginger and sumatriptan in the ablative treatment of the common migraine. Phytother Res 2014;28(3):412-5. PubMed
  43. Mahluji S, Attari VE, Mobasseri M, Payahoo L, Ostadrahimi A, Golzari SE. Effects of ginger (Zingiber officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients. Int J Food Sci Nutr 2013;64(6):682-6.
  44. Mozaffari-Khosravi H, Talaei B, Jalali BA, Najarzadeh A, Mozayan MR. The effect of ginger powder supplementation on insulin resistance and glycemic indices in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Complement PubMed
  45. Paramdeep G. Efficacy and tolerability of ginger (Zingiber officinale) in patients of osteoarthritis of knee. Indian J Physiol Pharmacol 2013;57(2):177-83.
  46. Rahnama P, Montazeri A, Huseini HF, Kianbakht S, Naseri M. Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med 2012;12:92. PubMed
  47. Viljoen E, Visser J, Koen N, Musekiwa A. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J 2014;13:20. PubMed
  48. Bartels EM, Folmer VN, Bliddal H, et al. Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials. Osteoarthritis Cartilage. 2015;23(1):13-21. PubMed
  49. Choi JS, Han JY, Ahn HK, et al. Assessment of fetal and neonatal outcomes in the offspring of women who had been treated with dried ginger (Zingiberis rhizoma siccus) for a variety of illnesses during pregnancy. J Obstet Gynaecol. 2015;35(2):125-30.
  50. Marx W, McKavanagh D, McCarthy AL, Bird R, Ried K, Chan A, Isenring L. The effect of ginger (Zingiber officinale) on platelet aggregation: A systematic literature review. PLoS One. 2015;10(10):e0141119. PubMed
  51. Crichton M, Marshall S, Marx W, McCarthy AL, Isenring E. Efficacy of ginger (Zingiber officinale) in ameliorating chemotherapy-induced nausea and vomiting and chemotherapy-related outcomes: A systematic review update and meta-analysis. J Acad Nutr Diet. 2 PubMed
  52. Martins LB, Rodrigues AMDS, Monteze NM, et al. Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) in the prophylactic treatment of migraine. Cephalalgia. 2020;40(1):88-95.
  53. Martins LB, Rodrigues AMDS, Rodrigues DF, Dos Santos LC, Teixeira AL, Ferreira AVM. Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) addition in migraine acute treatment. Cephalalgia. 2019;39(1):68-76.
  54. Ahad A, Raish M, Bin Jardan YA, Alam MA, Al-Mohizea AM, Al-Jenoobi FI. Effect of Hibiscus sabdariffa and Zingiber officinale on the antihypertensive activity and pharmacokinetic of losartan in hypertensive rats. Xenobiotica. 2020:1-11.
  55. Okuhira H, Nakatani Y, Furukawa F, Kanazawa N. Anaphylaxis to ginger induced by herbal medicine. Allergol Int. 2020;69(1):159-160. PubMed
  56. Yamprasert R, Chanvimalueng W, Mukkasombut N, Itharat A. Ginger extract versus Loratadine in the treatment of allergic rhinitis: a randomized controlled trial. BMC Complement Med Ther. 2020;20(1):116. PubMed
  57. Ebrahimzadeh A, Ebrahimzadeh A, Mirghazanfari SM, Hazrati E, Hadi S, Milajerdi A. The effect of ginger supplementation on metabolic profiles in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. PubMed
  58. Alam MA, Bin Jardan YA, Alzenaidy B, et al. Effect of Hibiscus sabdariffa and Zingiber officinale on pharmacokinetics and pharmacodynamics of amlodipine. J Pharm Pharmacol 2021;73(9):1151-60.
  59. Akbarzadeh E, Heydari M, Atarzadeh F, Jaladat AM. Chronic dysuria following ginger (Zingiber officinale) use: a case report. Galen Med J 2018;7:e1086. DOI
  60. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  61. Rostamkhani H, Veisi P, Niknafs B, Jafarabadi MA, Ghoreishi Z. The effect of zingiber officinale on prooxidant-antioxidant balance and glycemic control in diabetic patients with ESRD undergoing hemodialysis: a double-blind randomized control trial. BMC Co PubMed
  62. Husain I, Dale OR, Idrisi M, et al. Evaluation of the Herb-Drug Interaction (HDI) Potential of Zingiber officinale and Its Major Phytoconstituents. J Agric Food Chem. 2023;71(19):7521-7534.
  63. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed
  64. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed

See these in context on the Ginger monograph →

Grape 34 references
  1. Kiesewetter H, Koscielny J, Kalus U, et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung
  2. Xiao Dong S, Zhi Ping Z, Zhong Xiao W, et al. Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 1999;48:638-40. PubMed
  3. Vaswani SK, Hamilton RG, Carey RN, et al. Anaphylaxis recurrent urticaria and angioedema from grape hypersensitivity. J Allergy Clin Immunol 1998;101:S31.
  4. Chevallier A. The Encyclopedia of Medicinal Plants. London, UK: Dorling Kindersley, Ltd., 1996.
  5. Bernstein DI, Bernstein CK, Deng C, et al. Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study. Ann Allergy Asthma Immunol 2002;88:272-8.. PubMed
  6. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33. PubMed
  7. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  8. Ray, S. D., Parikh, H., Hickey, E., Bagchi, M., and Bagchi, D. Differential effects of IH636 grape seed proanthocyanidin extract and a DNA repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent aniline hydroxylation. Mol Cell B PubMed
  9. O'Byrne, D. J., Devaraj, S., Grundy, S. M., and Jialal, I. Comparison of the antioxidant effects of Concord grape juice flavonoids alpha-tocopherol on markers of oxidative stress in healthy adults. Am J Clin.Nutr. 2002;76(6):1367-1374.
  10. Schaefer, E., Peil, H., Ambrosetti, L., and Petrini, O. Oedema protective properties of the red vine leaf extract AS 195 (Folia vitis viniferae) in the treatment of chronic venous insufficiency. A 6-week observational clinical trial. Arzneimittelforschun PubMed
  11. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  12. de Lange, D. W., Scholman, W. L., Kraaijenhagen, R. J., Akkerman, J. W., and van de Wiel, A. Alcohol and polyphenolic grape extract inhibit platelet adhesion in flowing blood. Eur.J Clin.Invest 2004;34(12):818-824. PubMed
  13. Samet, J. M. and Coultas, D. B. Reduced forced vital capacity in California grape workers. What does it mean? Am Rev.Respir.Dis 1992;145(2 Pt 1):255-256. PubMed
  14. Gamsky, T. E., McCurdy, S. A., Samuels, S. J., and Schenker, M. B. Reduced FVC among California grape workers. Am Rev.Respir.Dis 1992;145(2 Pt 1):257-262. PubMed
  15. de Lange, D. W., Verhoef, S., Gorter, G., Kraaijenhagen, R. J., van de Wiel, A., and Akkerman, J. W. Polyphenolic grape extract inhibits platelet activation through PECAM-1: an explanation for the French paradox. Alcohol Clin.Exp.Res 2007;31(8):1308-1314 PubMed
  16. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu
  17. Krikorian, R., Nash, T. A., Shidler, M. D., Shukitt-Hale, B., and Joseph, J. A. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103(5):730-734. PubMed
  18. Ingersoll, G. L., Wasilewski, A., Haller, M., Pandya, K., Bennett, J., He, H., Hoffmire, C., and Berry, C. Effect of concord grape juice on chemotherapy-induced nausea and vomiting: results of a pilot study. Oncol.Nurs.Forum 2010;37(2):213-221. PubMed
  19. Oliveira-Freitas, V. L., Dalla, Costa T., Manfro, R. C., Cruz, L. B., and Schwartsmann, G. Influence of purple grape juice in cyclosporine bioavailability. J Ren Nutr. 2010;20(5):309-313. PubMed
  20. Hollis, J. H., Houchins, J. A., Blumberg, J. B., and Mattes, R. D. Effects of concord grape juice on appetite, diet, body weight, lipid profile, and antioxidant status of adults. J Am Coll.Nutr. 2009;28(5):574-582. PubMed
  21. Dohadwala, M. M., Hamburg, N. M., Holbrook, M., Kim, B. H., Duess, M. A., Levit, A., Titas, M., Chung, W. B., Vincent, F. B., Caiano, T. L., Frame, A. A., Keaney, J. F., Jr., and Vita, J. A. Effects of Concord grape juice on ambulatory blood pressure in
  22. Rabe, E., Stucker, M., Esperester, A., Schafer, E., and Ottillinger, B. Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study. Eur.J Vasc.Endovasc. PubMed
  23. Trotta, M., Cesaretti, M., Conzi, R., Derchi, L. E., and Borgonovo, G. Elderly male with mesogastric pain. Small bowel obstruction caused by an intact fresh grape. Ann.Emerg.Med 2011;58(4):e1-e2. PubMed
  24. McCurdy, S. A., Wiggins, P., Schenker, M. B., Munn, S., Shaieb, A. M., Weinbaum, Z., Goldsmith, D., McGillis, S. T., Berman, B., and Samuels, S. Assessing dermatitis in epidemiologic studies: occupational skin disease among California grape and tomato ha
  25. Winter, C. K. and Kurtz, P. H. Factors influencing grape worker susceptibility to skin rashes. Bull.Environ.Contam Toxicol. 1985;35(3):418-426. PubMed
  26. Yamasaki, R., Dekio, S., and Jidoi, J. Contact dermatitis from grape bud. Contact Dermatitis 1985;12(4):226-227. PubMed
  27. Cox, J. and Grigg, M. Small bowel obstruction by an intact grape. J Am Geriatr.Soc 1986;34(7):550. PubMed
  28. Faircloth, D. E. and Robison, W. J. Obstruction of the sigmoid colon by grape seeds. JAMA 11-27-1981;246(21):2430. PubMed
  29. Marguerie, C. and Drouet, M. [Occupational eosinophilic lung in a grape grower: role of sulfites]. Allerg.Immunol.(Paris) 1995;27(5):163-167.
  30. Brito, FF., Martinez, A., Palacios, R., Mur, P., Gomez, E., Galindo, P. A., Borja, J., and Martinez, J. Rhinoconjunctivitis and asthma caused by vine pollen: a case report. J Allergy Clin Immunol 1999;103(2 Pt 1):262-266. PubMed
  31. Ras RT, Zock PL, Zebregs YE, et al. Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension. Br J Nutr 2013;110(12):2234-41. PubMed
  32. Berry AC, Nakshabendi R, Abidali H, et al. Adverse effects of grape seed extract supplement: A clinical case and long-term follow-up. J Diet Suppl. 2016;13(2):232-5. PubMed
  33. Martínez-Maqueda D, Zapatera B, Gallego-Narbón A, Vaquero MP, Saura-Calixto F, Pérez-Jiménez J. A 6-week supplementation with grape pomace to subjects at cardiometabolic risk ameliorates insulin sensitivity, without affecting other metabolic syndrome mark
  34. Moon SW, Shin YU, Cho H, Bae SH, Kim HK; and for the Mogen Study Group. Effect of grape seed proanthocyanidin extract on hard exudates in patients with non-proliferative diabetic retinopathy. Medicine (Baltimore) 2019;98(21):e15515. PubMed

See these in context on the Grape monograph →

Diindolylmethane 14 references
  1. Natl Inst Health, Natl Inst Environmental Health Sci. Indole-3-carbinol. Available at: http://ntp-server.niehs.nih.gov.
  2. Balk JL. Indole-3-carbinol for cancer prevention. Altern Med Alert 2000; 3:105-7.
  3. Riby JE, Chang GHF, Firestone GL, Bjeldanes LF. Ligand-independent activation of estrogen receptor function by 3,3'-diindolylmethane in human breast cancer cells. Biochem Pharmacol 2000;60:167-77. PubMed
  4. Lake BG, Tredger JM, Renwick AB, et al. 3'3-diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. Xenobiotica 1998;28:803-11. PubMed
  5. Dalessandri, K. M., Firestone, G. L., Fitch, M. D., Bradlow, H. L., and Bjeldanes, L. F. Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Canc PubMed
  6. Reed, G. A., Arneson, D. W., Putnam, W. C., Smith, H. J., Gray, J. C., Sullivan, D. K., Mayo, M. S., Crowell, J. A., and Hurwitz, A. Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmetha
  7. Reed, G. A., Sunega, J. M., Sullivan, D. K., Gray, J. C., Mayo, M. S., Crowell, J. A., and Hurwitz, A. Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. Cancer Epidemiol.Biomarkers Prev. 2008; PubMed
  8. Del Priore G., Gudipudi, D. K., Montemarano, N., Restivo, A. M., Malanowska-Stega, J., and Arslan, A. A. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol.Oncol. 2010;116(3):464-467. PubMed
  9. Heath, E. I., Heilbrun, L. K., Li, J., Vaishampayan, U., Harper, F., Pemberton, P., and Sarkar, F. H. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3'- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am.J.Transl.R
  10. Jellinck, P. H., Forkert, P. G., Riddick, D. S., Okey, A. B., Michnovicz, J. J., and Bradlow, H. L. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem.Pharmacol. 3-9-1993;45(5):1129-1136. PubMed
  11. Bui PV, Moualla M, Upson DJ. A Possible Association of Diindolylmethane with Pulmonary Embolism and Deep Venous Thrombosis. Case Rep Med. 2016;2016:7527098. PubMed
  12. Castañon A, Tristram A, Mesher D, Powell N, Beer H, Ashman S, Rieck G, Fielder H, Fiander A, Sasieni P. Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. Br J Cancer. 20 PubMed
  13. Le TM, Sanders CJ, van de Corput L, van Erpecum KJ, Röckmann H. Drug rash with eosinophilia and systemic symptoms caused by the dietary supplement diindolylmethane. J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):175-6. PubMed
  14. Pence ST, Mehta K, Crum-Bailey J. The Serious Side of Supplements: An Ischemic Stroke in a Healthy 38-year-old Female. Mil Med 2022. PubMed

See these in context on the Diindolylmethane monograph →

Lutein 2 references
  1. Brown L, Rimm EB, Seddon JM, et al. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr 1999;70:517-24. PubMed
  2. Chasan-Taber L, Willett WC, Seddon JM, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr 1999;70:509-16. PubMed

See these in context on the Lutein monograph →

Resveratrol 24 references
  1. Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: a molecule whose time has come? And gone? Clin Biochem 1997;30:91-113.
  2. Pace-Asciak CR, Rounova O, Hahn SE, et al. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clin Chim Acta 1996;246:163-82. PubMed
  3. Bertelli AA, Giovannini L, Bernini W, et al. Antiplatelet activity of cis-resveratrol. Drugs Exp Clin Res 1996;22:61-3.
  4. Pace-Asciak CR, Hahn S, Diamandis EP, et al. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 1995;235:207-19.
  5. Bertelli A, Bertelli AA, Gozzini A, Giovannini L. Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exp Clin Res 1998;24:133-8.
  6. Bertelli AA, Giovannini L, Giannessi D, et al. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React 1995;17:1-3.
  7. Piver B, Berthou F, Dreano Y, Lucas D. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett 2001;125:83-91. PubMed
  8. Chang, T. K., Chen, J., and Lee, W. B. Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J.Pharmacol.Exp.Ther. 2001;299(3):874-882.
  9. Dobrydneva, Y., Williams, R. L., and Blackmore, P. F. trans-Resveratrol inhibits calcium influx in thrombin-stimulated human platelets. Br.J.Pharmacol. 1999;128(1):149-157.
  10. Kirk, R. I., Deitch, J. A., Wu, J. M., and Lerea, K. M. Resveratrol decreases early signaling events in washed platelets but has little effect on platalet in whole food. Blood Cells Mol.Dis. 2000;26(2):144-150.
  11. Zbikowska, H. M. and Olas, B. Antioxidants with carcinostatic activity (resveratrol, vitamin E and selenium) in modulation of blood platelet adhesion. J Physiol Pharmacol. 2000;51(3):513-520.
  12. Olas, B., Wachowicz, B., Saluk-Juszczak, J., and Zielinski, T. Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thromb.Res 8-15-2002;107(3-4):141-145. PubMed
  13. Yu, C., Shin, Y. G., Kosmeder, J. W., Pezzuto, J. M., and van Breemen, R. B. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun.Mass Spectro PubMed
  14. Ma, Z. H. and Ma, Q. Y. Resveratrol: a medical drug for acute pancreatitis. World J Gastroenterol. 6-7-2005;11(21):3171-3174. PubMed
  15. la, Porte C., Voduc, N., Zhang, G., Seguin, I., Tardiff, D., Singhal, N., and Cameron, D. W. Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Cli PubMed
  16. Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A., Perloff, M., Booth, T. D., Vasilinin, G., Sen, A., Schinas, A. M., Piccirilli, G., Brown, K., Steward, W. P., Gescher, A. J., and Brenner, D. E. Repeat dose study of the cancer chemopreventive
  17. Pendurthi, U. R., Williams, J. T., and Rao, L. V. Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells : A possible mechanism for the cardiovascular benefits associated with moderate consumption of wine. PubMed
  18. Chachay VS, Macdonald GA, Martin JH, Whitehead JP, O'Moore-Sullivan TM, Lee P, Franklin M, Klein K, Taylor PJ, Ferguson M, Coombes JS, Thomas GP, Cowin GJ, Kirkpatrick CM, Prins JB, Hickman IJ. Resveratrol does not benefit patients with nonalcoholic fatty
  19. Bedada SK, Neerati P. Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers. Phytother Res. 2016;30(3):463-8. PubMed
  20. Lin CT, Sun XY, Lin AX. Supplementation with high-dose trans-resveratrol improves ultrafiltration in peritoneal dialysis patients: a prospective, randomized, double-blind study. Ren Fail. 2016;38(2):214-21. PubMed
  21. Li Q, Yang G, Xu H, Tang S, Lee WY. Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Med Ther 2021;21(1):214. PubMed
  22. McCreary MR, Schnell PM, Rhoda DA. Randomized double-blind placebo-controlled proof-of-concept trial of resveratrol for outpatient treatment of mild coronavirus disease (COVID-19). Sci Rep 2022;12(1):10978. PubMed
  23. Abdelhaleem IA, Brakat AM, Adayel HM, Asla MM, Rizk MA, Aboalfetoh AY. The effects of resveratrol on glycemic control and cardiometabolic parameters in patients with T2DM: A systematic review and meta-analysis. Med Clin (Barc) 2022;158(12):576-585. PubMed
  24. Badaoui A. Allergic contact dermatitis to resveratrol and Scutellaria baicalensis root extract in a cosmetic product. Contact Dermatitis 2022.

See these in context on the Resveratrol monograph →

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

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

© 2021 Therapeutic Research Center, LLC

Keep exploring