Major interaction on record — check this product against your medications before combining. Based on 16 of 18 ingredients. Check your meds →
Dietary supplement

Testaplexx Ingredients & Drug Interactions

by Frontline Formulations

Testaplexx label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 23, 2026 · Label data from the NIH DSLD
What is this page for?

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

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

The interaction bottom line Most serious interaction: Major

Testaplexx is a dietary supplement by Frontline Formulations with 18 active ingredients. Its ingredients are commonly taken for bone health and osteoporosis, correcting vitamin d deficiency, immune system support.Based on those ingredients, 1,625 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are KSM-66, Bioperine, Horny Goat Weed extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Testaplexx by Frontline Formulations

Ask about any prescription or over-the-counter medication and we check it for interactions with Testaplexx by Frontline Formulations — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
Prefer a human? Send your question to our licensed pharmacists — free, answered by email within 24 hours.

HelloPharmacist Scorecard of Testaplexx by Frontline Formulations

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

From our pharmacy team — supplement deep dive

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

What’s inside

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 18 of its 18 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Testaplexx contains 18 ingredients, of which the active ones include vitamins and herbal extracts. The main actives are Vitamin D3 for bone and mineral health; Zinc for immune function and healing; DHEA and Tongkat Ali (also called Eurycoma longifolia) for hormone support and sexual function; Tribulus terrestris for sexual health; and Saw Palmetto for prostate health.

You'll also find Maca Root Extract, Stinging Nettle leaf extract, and Horny Goat Weed extract — all traditionally used for vitality and sexual function — alongside Ashwagandha (KSM-66) for stress and sleep, Milk Thistle for liver support, Bergamot Fruit Extract, Diindolylmethane, N-Acetyl L-Cysteine, Bioperine (black pepper extract) to boost absorption, and Arimistane. The product has no inactive fillers listed.

Does it work?

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

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

Why this rating?
  • The label markets this product for: Optimize testosterone and libido with prostate support.
  • We looked for evidence on: Age-related testosterone deficiency, Benign prostatic hyperplasia (BPH), Antidepressant-induced sexual dysfunction, Erectile dysfunction, Sexual function, Vitality.
  • The strongest evidence on file: Tribulus is rated "Possibly Effective" for Sexual dysfunction (Natural Medicines).
  • Also on file: Saw Palmetto is rated "Possibly Ineffective" for Benign prostatic hyperplasia (BPH).
  • Also on file: Zinc is rated "Possibly Ineffective" for Sexual dysfunction.

The evidence for Testaplexx's ingredients is mixed. Vitamin D3 is effective for treating rickets, renal bone disease, and certain calcium disorders.

Zinc is effective for zinc deficiency and likely effective for Wilson disease, though evidence for acne and age-related eye disease is weaker. DHEA shows likely effectiveness for vaginal atrophy in women but only possibly effective for depression and skin aging.

Tribulus is possibly effective for sexual function but ineffective for athletic performance. Saw Palmetto is possibly ineffective for benign prostate enlargement.

Ashwagandha is possibly effective for anxiety, stress, and insomnia. Milk Thistle is possibly effective for type 2 diabetes.

For most other ingredients — including Maca Root Extract, Stinging Nettle, Horny Goat Weed, Bergamot, Tongkat Ali, Diindolylmethane, N-Acetyl Cysteine, and Arimistane — the evidence ranges from insufficient to establish effectiveness to not established in the data we hold.

The evidence, ingredient by ingredient Vitamin D Zinc Dhea Maca Tribulus Saw Palmetto Diindolylmethane Eurycoma Longifolia

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 15 of the 16 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 16 of 16.
  • General safety write-ups exist for 16 of 16.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

At recommended doses, most ingredients are generally well tolerated. Vitamin D3 is safe in typical amounts but can cause toxicity if taken in very high doses over time, leading to elevated calcium and related symptoms; pregnancy use is acceptable only under a doctor's guidance.

Zinc is safe below 40 mg daily for adults, though higher doses may cause nausea, diarrhea, and a metallic taste. DHEA carries caution — it's a hormone and can cause acne, mood changes, and in women, deeper voice and facial hair; pregnancy use is unsafe.

Tribulus, Saw Palmetto, Maca Root Extract, Tongkat Ali, Horny Goat Weed, Bergamot, and Stinging Nettle should all be avoided during pregnancy and breastfeeding due to insufficient safety data or traditional concerns about hormone effects. DHEA, Arimistane, and Bergamot are explicitly unsafe or possibly unsafe in pregnancy.

Ashwagandha has rare but serious concerns about liver damage and should be used cautiously. NAC is generally well tolerated but most adverse effects occur at very high doses.

Most ingredients have not been rigorously tested long-term as supplements.

Side effects, ingredient by ingredient Vitamin D Zinc Dhea Maca Tribulus Saw Palmetto Diindolylmethane Eurycoma Longifolia

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?
  • 15 of the 16 matched ingredients can interact with medications — Tribulus, Milk Thistle, Bergamot, Dhea, Stinging Nettle, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 1,626 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 your medications against these types before taking Testaplexx. Most serious: if you use intravenous or transdermal nitroglycerin, do not combine with this product — NAC carries a Major-severity interaction causing severe low blood pressure and headaches.

Stop or consult your pharmacist immediately if you take this combo. For Moderate-severity concerns, double-check if you use any blood thinner or antiplatelet drugs (warfarin, aspirin, clopidogrel), blood pressure medications, diabetes drugs, antibiotics (especially quinolones, tetracyclines, or cephalexin), HIV medications, heart rhythm drugs (digoxin, verapamil, diltiazem), statin cholesterol drugs (atorvastatin), psychiatric medications (SSRIs, benzodiazepines), immunosuppressants, thyroid hormone, or anticancer drugs.

Check your own medication Run your meds through the checker above

The bottom line

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

Testaplexx is a combination product aimed at male performance and vitality, but its 18 ingredients carry numerous documented interactions — most notably NAC with nitroglycerin (Major severity) — and should not be used without checking your specific medications first. If you take any prescription drugs, especially blood thinners, blood pressure or diabetes medications, heart drugs, antibiotics, psychiatric medications, or HIV antiretrovirals, talk to your pharmacist before starting this product.

Women who are pregnant or breastfeeding, or anyone with liver disease, should avoid it entirely.

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

Assessment coverage: 16 of 18 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Aug 23, 2023.

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 Testaplexx, straight from the product label.

Brand Frontline Formulations
Net contents 240 Capsule(s)
Market status On market
Date entered into DSLD Aug 23, 2023
DSLD ID 300255
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Testaplexx by Frontline Formulations, 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:
8 Capsule(s)
Maximum serving Sizes:
8 Capsule(s)
Servings per container
30
IngredientAmount% DV
Vitamin D35000 IU625%
Zinc50 mg333%
Dehydroepiandrosterone25 mg--
Maca Root Extract500 mg--
Tribulus terrestris extract1000 mg--
AstraGin50 mg--
Saw Palmetto Fruit Extract450 mg--
3,3'-Diindolylmethane300 mg--
Tongkat Ali300 mg--
Stinging Nettle leaf extract300 mg--
5-Alpha-hydroxy-laxogenin100 mg--
N-Acetyl L-Cysteine300 mg--
Horny Goat Weed extract100 mg--
Bioperine5 mg--
Bergamot Fruit Extract300 mg--
KSM-66300 mg--
Milk Thistle300 mg--
Androsta-3,5-Dien-7,17-Dione50 mg--

Tap any ingredient to jump to its full detail below.

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

Test Matrix Optimize Testosterone & Estrogen Levels Libido Enhancement Prostate & Liver Support

FDA Statement of Identity

Dietary Supplement

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

See for yourself

Testaplexx by Frontline Formulations label

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

Testaplexx label

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

View the full label (PDF)
What’s inside

The Ingredients in Testaplexx by Frontline Formulations

These are the 18 active ingredients this product is made of. Select any to open its full monograph.

Serving size8 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 D3

Interacts with
715 drugs
5000 IU per serving Form: Cholecalciferol

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

Vitamin D3 monograph & interactions

Zinc

Interacts with
67 drugs
50 mg per serving Form: Zinc Citrate

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

Zinc monograph & interactions

Dehydroepiandrosterone

Interacts with
776 drugs
25 mg per serving

DHEA is a natural hormone that the body makes and that declines with age, and it is sold as a supplement claiming many benefits. The evidence is mixed...

Dehydroepiandrosterone monograph & interactions

Maca Root Extract

No known
interactions
500 mg per serving

Maca is a nutrient-rich Andean root often used for energy, libido, and menopause symptoms. Early studies suggest it may modestly help sexual desire an...

Maca Root Extract monograph & interactions

Tribulus terrestris extract

Interacts with
259 drugs
1000 mg per serving

Tribulus is a plant supplement most often marketed to boost libido, testosterone, and athletic performance, but the human evidence behind these claims...

Tribulus terrestris extract monograph & interactions

AstraGin

50 mg per serving Form: Astragalus membranaceous Root Extract, Panax notoginseng Root Extract

Saw Palmetto Fruit Extract

Interacts with
174 drugs
450 mg per serving

Saw palmetto is a plant extract most often used for urinary symptoms linked to an enlarged prostate (BPH). The best research suggests it works no bett...

Saw Palmetto Fruit Extract monograph & interactions

3,3'-Diindolylmethane

Interacts with
269 drugs
300 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'-Diindolylmethane monograph & interactions

Tongkat Ali

Interacts with
248 drugs
300 mg per serving

Eurycoma longifolia (tongkat ali) is a Southeast Asian herb most popular for supporting testosterone, libido, and male fertility, with some small huma...

Tongkat Ali monograph & interactions

Stinging Nettle leaf extract

Interacts with
164 drugs
300 mg per serving

Stinging nettle is a common plant used as food and in traditional medicine, most often for prostate symptoms, allergies, and joint pain. The evidence...

Stinging Nettle leaf extract monograph & interactions

5-Alpha-hydroxy-laxogenin

100 mg per serving

N-Acetyl L-Cysteine

Interacts with
294 drugs
300 mg per serving

N-acetyl cysteine (NAC) is a supplement form of the amino acid cysteine and a building block for the antioxidant glutathione. It has well-established...

N-Acetyl L-Cysteine monograph & interactions

Horny Goat Weed extract

Interacts with
963 drugs
100 mg per serving

Horny goat weed (Epimedium) is a traditional Chinese herb most often marketed for low libido and erectile problems, but solid human evidence for these...

Horny Goat Weed extract monograph & interactions

Bioperine

Interacts with
1,019 drugs
5 mg per serving Form: Black Pepper extract

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to he...

Bioperine monograph & interactions

Bergamot Fruit Extract

Interacts with
410 drugs
300 mg per serving Form: Polyphenols

Bergamot is a Mediterranean citrus fruit, and its standardized extract is most often used to support cholesterol and heart health, with some early but...

Bergamot Fruit Extract monograph & interactions

KSM-66

Interacts with
1,372 drugs
300 mg per serving Form: Ashwagandha

Ashwagandha is an Ayurvedic herb most often taken to help with stress, anxiety, and sleep, and some small studies suggest it may help, though the evid...

KSM-66 monograph & interactions

Milk Thistle

Interacts with
954 drugs
300 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 monograph & interactions

Androsta-3,5-Dien-7,17-Dione

Interacts with
4 drugs
50 mg per serving

Arimistane (sometimes sold as Estrovade) is a synthetic aromatase inhibitor marketed as a dietary supplement to lower estrogen and raise testosterone,...

Androsta-3,5-Dien-7,17-Dione monograph & interactions
Interaction report

Testaplexx by Frontline Formulations Drug Interactions

Want to check YOUR meds against Testaplexx?

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
1,625Drugs
1 Major 1,578 Moderate 46 Minor

Ingredients driving the most interactions

KSM-66 1,372
Bioperine 1,019
Horny Goat Weed extract 963
Milk Thistle 954
Dehydroepiandrosterone 776

Individual Drug Interactions

The ingredients in Testaplexx interact with 1,625 drugs. Click any drug to see the details.

15 of the 18 ingredients in Testaplexx interact with drugs. Each result below shows which ingredient is responsible. KSM-66 Bioperine Horny Goat Weed extract Milk Thistle Dehydroepiandrosterone Vitamin D3 Bergamot Fruit Extract N-Acetyl L-Cysteine 3,3'-Diindolylmethane Tribulus terrestris extract Tongkat Ali Saw Palmetto Fruit Extract Stinging Nettle leaf extract Zinc Androsta-3,5-Dien-7,17-Dione

Each ingredient & the kinds of drugs it affects

For each ingredient in Testaplexx 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.

KSM-6610 drug types · 1,372 drugs

Antidiabetes Drugs

Theoretically, taking ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.
There is preliminary clinical evidence suggesting that ashwagandha might lower blood glucose levels. Theoretically, ashwagandha might have additive effects when used with antidiabetes drugs and increase the risk of hypoglycemia.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.
Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure. Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.

Likelihood Possible Evidence D
Benzodiazepines

Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.
There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin). This may also occur with other benzodiazepines.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.
Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.
Ashwagandha has been linked to cases of acute hepatitis, liver failure, hepatic encephalopathy, autoimmune hepatitis, the need for liver transplantation, and death due to liver failure.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.
Ashwagandha has demonstrated immunostimulant effects in humans. Animal research has shown that ashwagandha can attenuate the immunosuppression caused by cyclophosphamide.

Likelihood Possible Evidence D
Thyroid Hormone

Ashwagandha might increase the effects and adverse effects of thyroid hormone.
Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion. In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism.

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

Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that ashwagandha extract induces CYP1A2 enzymes.

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

Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that ashwagandha extract induces CYP3A4 enzymes.

Likelihood Possible Evidence D
Serotonergic Drugs

Some animal studies have reported that ashwagandha can enhance serotonergic transmission by altering certain serotonin (5-HT) receptors. However, there is no evidence to suggest that ashwagandha increases the risk of serotonin-related effects, and there have been no published case reports of serotonin syndrome when combined with other serotonergic drugs. Nevertheless, due to the lack of extensive studies on the matter and the fact that ashwagandha appears to affect serotonergic pathways, it would be prudent to exercise caution when combining it with drugs that affect serotonin. [References: - Effects of Withania somnifera (Ashwaga ndha) on Stress and the Stress-Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Curr Neuropharmacol. 2021 Sep 14; 19: 1468–1495. - A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573577/]

Likelihood Possible Evidence C
KSM-66 full monograph & interactions

Bioperine17 drug types · 1,019 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation. This has not been reported in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Likelihood Possible Evidence D
Atorvastatin (Lipitor)

Theoretically, black pepper might increase blood levels of atorvastatin.
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold. This has not been reported in humans.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, black pepper might increase the effects and side effects of cyclosporine.
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine. This has not been reported in humans.

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

Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
In vitro research suggests that some constituents of black pepper inhibit CYP2D6. This has not been reported in humans.

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

Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research and pharmacokinetic simulation data suggest that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.

Likelihood Possible Evidence D
Lithium

Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
Black pepper is thought to have diuretic properties.

Likelihood Probable Evidence D
Nevirapine (Viramune)

Black pepper might increase blood levels of nevirapine.
Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study.

Likelihood Probable Evidence D
P-Glycoprotein Substrates

Theoretically, black pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein.

Likelihood Possible Evidence D
Pentobarbital (Nembutal)

Theoretically, black pepper might increase the sedative effects of pentobarbital.
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

Black pepper might increase blood levels of phenytoin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin. Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin. Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper.

Likelihood Possible Evidence B
Propranolol (Inderal)

Black pepper might increase blood levels of propranolol.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol.

Likelihood Possible Evidence B
Rifampin (Rifadin)

Black pepper might increase blood levels of rifampin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and serum levels of rifampin.

Likelihood Possible Evidence B
Theophylline

Black pepper might increase blood levels of theophylline.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline.

Likelihood Possible Evidence D
Amoxicillin (Amoxil, Trimox)

Theoretically, black pepper might increase the effects and side effects of amoxicillin.
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin. This has not been reported in humans.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects. In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner.

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

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.

Likelihood Possible Evidence D
Bioperine full monograph & interactions

Horny Goat Weed extract6 drug types · 963 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, horny goat weed might increase the risk of bleeding.
In vitro research and animal research shows that horny goat weed can inhibit platelet aggregation and thrombus formation. This effect has not been reported in humans.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, horny goat weed might increase the risk of hypotension.
Laboratory research suggests that horny goat weed might have hypotensive effects. This effect has not been reported in humans.

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

Theoretically, horny goat weed might increase the effects and side effects of CYP1A2 substrates.
In vitro, horny goat weed leaf extract inhibits CYP1A2. This effect has not been reported in humans.

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

Theoretically, horny goat weed might increase the effects and side effects of CYP2B6 substrates.
In vitro, horny goat weed leaf extract inhibits CYP2B6. This effect has not been reported in humans.

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

Theoretically, horny goat weed might increase the effects and side effects of CYP3A4 substrates.
In vitro, horny goat weed extract inhibits CYP3A4 and suppresses CYP3A4 mRNA expression. This effect has not been reported in humans.

Likelihood Possible Evidence D
Estrogens

Theoretically, concomitant use of horny goat weed with estrogens might increase their therapeutic and adverse effects.
In vitro evidence suggests that horny goat weed has estrogenic activity. In clinical research, horny goat weed has been shown to increase blood levels of estrogen in some females.

Likelihood Possible Evidence D
Horny Goat Weed extract full monograph & interactions

Milk Thistle17 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
Milk Thistle full monograph & interactions

Dehydroepiandrosterone10 drug types · 776 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, DHEA might increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Human and laboratory research show that DHEA and DHEA-S can inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidepressant Drugs

Theoretically, DHEA might increase the risk of psychiatric adverse events when used with antidepressants.
In a human case report, the use of a selective serotonin reuptake inhibitor (SSRI) with DHEA caused a manic episode. Concern for this interaction may be greater in younger individuals with higher baseline DHEA levels.

Likelihood Possible Evidence D
Aromatase Inhibitors

Theoretically, DHEA might interfere with the clinical effects of aromatase inhibitors.
DHEA is a potent estrogen agonist, which may antagonize the anti-estrogen activity of aromatase inhibitors.

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

Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.
Some preliminary evidence shows that DHEA may inhibit CYP3A4; however, the clinical significance of this potential interaction is not known.

Likelihood Possible Evidence D
Fulvestrant (Faslodex)

Theoretically, DHEA might interfere with the anti-estrogen effects of fulvestrant.
DHEA is a potent estrogen agonist. Some research shows that it can overcome the estrogen receptor antagonist action of fulvestrant in estrogen-receptor positive cancer cells.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, DHEA might interfere with the anti-estrogen effects of tamoxifen.
DHEA is a potent estrogen agonist. Some research shows that it can overcome the estrogen receptor antagonist activity of tamoxifen in estrogen-receptor positive cancer cells.

Likelihood Possible Evidence D
Triazolam (Halcion)

DHEA can increase blood levels of triazolam.
Administration of DHEA 200 mg daily for two weeks was shown to inhibit the cytochrome P450 3A4 (CYP3A4) metabolism of triazolam. This inhibition appears to be due to DHEA-S, rather than DHEA.

Likelihood Probable Evidence D
Tuberculosis Vaccine

DHEA might reduce the effectiveness of the tuberculosis vaccine.
Animal research shows that high doses of DHEA can reduce the efficacy of the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine.

Likelihood Possible Evidence D
Estrogens

Theoretically, DHEA might increase the effects and adverse effects of estrogen therapy.
DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones. Also, in clinical research, estrogen-progestin oral contraceptives and conjugated estrogens reduce blood levels of DHEA and DHEA-S. The clinical significance of these findings is unclear.

Likelihood Possible Evidence D
Testosterone

Theoretically, DHEA might increase the effects and side effects of testosterone therapy.
DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones. The clinical significance of these findings is unclear.

Likelihood Possible Evidence D
Dehydroepiandrosterone full monograph & interactions

Vitamin D38 drug types · 715 drugs

Aluminum

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

Likelihood Probable Evidence B
Atorvastatin (Lipitor)

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

Likelihood Probable Evidence B
Calcipotriene (Dovonex)

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

Likelihood Probable Evidence D
Digoxin (Lanoxin)

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

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

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

Likelihood Probable Evidence B
Thiazide Diuretics

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

Likelihood Probable Evidence D
Verapamil (Calan, Others)

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

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

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

Likelihood Possible Evidence D
Vitamin D3 full monograph & interactions

Bergamot Fruit Extract2 drug types · 410 drugs

Antidiabetes Drugs

Theoretically, taking bergamot with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research suggests that bergamot juice has hypoglycemic effects.

Likelihood Possible Evidence D
Photosensitizing Drugs

Theoretically, topical bergamot essential oil might increase the risk of side effects when used along with photosensitizing drugs.
Bergamot contains bergapten, which has photosensitizing effects.

Likelihood Probable Evidence D
Bergamot Fruit Extract full monograph & interactions

N-Acetyl L-Cysteine5 drug types · 294 drugs

Nitroglycerin

N-acetyl cysteine can increase the risk for hypotension and headaches when taken with intravenous or transdermal nitroglycerin.
Clinical research shows that concomitant administration of N-acetyl cysteine and intravenous or transdermal nitroglycerin can cause severe hypotension and intolerable headaches. Furthermore, in vitro research suggests that N-acetyl cysteine increases the anticoagulant activity of nitroglycerin.

Likelihood Probable Evidence B
Activated Charcoal

N-acetyl cysteine might reduce the effects of activated charcoal, while activated charcoal might reduce the absorption of N-acetyl cysteine.
N-acetyl cysteine appears to reduce the capacity of activated charcoal to adsorb acetaminophen and salicylic acid. Conversely, although clinical research suggests that although activated charcoal can reduce the absorption of N-acetyl cysteine by up to 40%, it does not seem to reduce its clinical effects. Other clinical evidence suggests that activated charcoal does not affect the absorption of N-acetyl cysteine.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, N-acetyl cysteine might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Clinical research suggests that intravenous N-acetyl cysteine decreases prothrombin time, prolongs coagulation time, decreases platelet aggregation, and increases blood loss in surgical patients. Furthermore, in vitro research suggests that N-acetyl cysteine increases the anticoagulant activity of nitroglycerin.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, N-acetyl cysteine might increase the risk of hypotension when taken with antihypertensive drugs.
Animal research suggests that N-acetyl cysteine potentiates the hypotensive effects of the angiotensin-converting enzyme inhibitors (ACEIs) captopril and enalaprilat. Theoretically, combining N-acetyl cysteine with other antihypertensive drugs might increase the risk of hypotension.

Likelihood Possible Evidence D
Chloroquine (Aralen)

Theoretically, N-acetyl cysteine might interfere with the antimalarial effects of chloroquine.
Animal research suggests that N-acetyl cysteine might reduce the antimalarial effects of chloroquine by increasing cellular levels of glutathione.

Likelihood Possible Evidence D
N-Acetyl L-Cysteine full monograph & interactions

3,3'-Diindolylmethane3 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
3,3'-Diindolylmethane full monograph & interactions

Tribulus terrestris extract3 drug types · 259 drugs

Antidiabetes Drugs

Taking tribulus with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research shows that Tribulus can lower blood glucose levels in adults with type 2 diabetes who are taking antidiabetes medications.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking tribulus with antihypertensive drugs might increase the risk of hypotension.
Animal research shows that tribulus can lower blood pressure by inhibiting angiotensin-converting enzyme (ACE). Tribulus has also demonstrated hypotensive effects in pre-hypertensive adults.

Likelihood Possible Evidence D
Lithium

Theoretically, tribulus might increase the levels and clinical effects of lithium.
Tribulus is thought to have diuretic properties. Due to these potential diuretic effects, tribulus might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

Likelihood Probable Evidence D
Tribulus terrestris extract full monograph & interactions

Tongkat Ali5 drug types · 248 drugs

Propranolol (Inderal)

Eurycoma longifolia can reduce the levels and clinical effects of propranolol.
A small clinical study in healthy persons shows that taking a single dose of a water-based Eurycoma longifolia extract 200 mg, in combination with a single dose of propranolol 80 mg, reduces the propranolol area under the curve (AUC) by 29%, reduces the peak concentration by 42%, and increases time to peak concentration by 86% when compared with control. Since the elimination half-life of propranolol did not change, it seems that Eurycoma longifolia alters the kinetics of propranolol by decreasing its absorption in the gut, and not by altering its metabolism. It is not known if separating administration will prevent this interaction.

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

Theoretically, Eurycoma longifolia might increase levels CYP1A2 substrates.
In vitro research suggests that methanolic Eurycoma longifolia root extract weakly inhibits CYP1A2 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2A6 (Cyp2A6) Substrates

Theoretically, Eurycoma longifolia might increase levels of CYP2A6 substrates.
In vitro research suggests that methanolic Eurycoma longifolia root extract weakly inhibits CYP2A6 enzymes. This effect has not been reported in humans.

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

Theoretically, Eurycoma longifolia might increase levels of CYP2C19 substrates.
In vitro research suggests that methanolic Eurycoma longifolia root extract weakly inhibits CYP2C19 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D
Testosterone

Theoretically, Eurycoma longifolia may further increase levels of testosterone.
A clinical study in aging males with testosterone levels below 300 ng/dL shows that taking a specific water extract of Eurycoma longifolia roots (Physta; Biotropics Malaysia) 100-200 mg daily with breakfast for 12 weeks increases total testosterone levels by 8% to 11% when compared with placebo. It is unclear whether this increase would occur in individuals with normal testosterone levels.

Likelihood Possible Evidence D
Tongkat Ali full monograph & interactions

Saw Palmetto Fruit Extract3 drug types · 174 drugs

Anticoagulant/Antiplatelet Drugs

Saw palmetto might increase the risk of bleeding with anticoagulant or antiplatelet drugs.
Saw palmetto is reported to prolong bleeding time. Theoretically, it might increase the risk of bleeding when used concomitantly with anticoagulant or antiplatelet drugs.

Likelihood Possible Evidence D
Contraceptive Drugs

Saw palmetto might reduce the effectiveness of contraceptive drugs.
Saw palmetto might have antiestrogenic effects. Theoretically, it might interfere with contraceptive drugs taken concomitantly.

Likelihood Possible Evidence B
Estrogens

Saw palmetto might reduce the effectiveness of estrogens.
Saw palmetto might have antiestrogenic effects. Theoretically, it might interfere with estrogens taken concomitantly.

Likelihood Possible Evidence B
Saw Palmetto Fruit Extract full monograph & interactions

Stinging Nettle leaf extract4 drug types · 164 drugs

Antidiabetes Drugs

Theoretically, stinging nettle might have additive effects with antidiabetes drugs.
Clinical research shows that stinging nettle might decrease blood glucose levels in patients with diabetes.

Likelihood Possible Evidence B
Diuretic Drugs

Theoretically, combining stinging nettle with diuretic drugs may have additive effects.
Animal research suggests that the above ground parts and roots of stinging nettle may have a diuretic effect.

Likelihood Possible Evidence D
Lithium

Theoretically, stinging nettle might reduce excretion and increase levels of lithium.
Animal research suggests that stinging nettle has diuretic and natriuretic properties, which could alter the excretion of lithium. The dose of lithium might need to be decreased.

Likelihood Possible Evidence D
Warfarin (Coumadin)

There is some concern that stinging nettle might decrease the effects of anticoagulant drugs such as warfarin.
Stinging nettle contains a significant amount of vitamin K. When taken in large quantities, this might interfere with the activity of warfarin.

Likelihood Possible Evidence D
Stinging Nettle leaf extract full monograph & interactions

Zinc10 drug types · 67 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

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

Likelihood Probable Evidence D
Cephalexin (Keflex)

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

Likelihood Probable Evidence B
Cisplatin (Platinol-Aq)

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

Likelihood Possible Evidence D
Integrase Inhibitors

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

Likelihood Possible Evidence D
Penicillamine (Cuprimine, Depen)

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

Likelihood Probable Evidence B
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Ritonavir (Norvir)

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

Likelihood Probable Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence B
Amiloride (Midamor)

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

Likelihood Probable Evidence B
Atazanavir (Reyataz)

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

Likelihood Probable Evidence B
Zinc full monograph & interactions

Androsta-3,5-Dien-7,17-Dione1 drug type · 4 drugs

Aromatase Inhibitors

It is believed that Arimistane inhibits the aromatase enzyme, which may interact with other aromatase inhibitors. This interaction could potentially increase the risk of side effects associated with low estrogen levels or from additive side effects, such as an increased risk of liver toxicity. It is recommended to consult with a healthcare provider before combining Arimistane with other aromatase inhibitors to assess the potential risks and benefits.

Likelihood Probable Evidence C
Androsta-3,5-Dien-7,17-Dione full monograph & interactions
The maker

Brand information

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

Frontline Formulations

See all Frontline Formulations products
Name
Frontline Formulations
Pharmacist Counseling Corner

Testaplexx by Frontline Formulations: Common Questions

Does Testaplexx by Frontline Formulations interact with any medications?
Yes. Based on its ingredients, Testaplexx has a known interaction with 1,625 medications, including 1 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Testaplexx contains 18 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 Testaplexx if I'm on blood pressure medication?
Not without checking first. Several ingredients — N-acetyl cysteine, Tribulus, Ashwagandha, and Horny Goat Weed — may lower blood pressure and could cause you to go too low when combined with your medicine. Talk to your pharmacist before starting.
Will Testaplexx affect my blood thinner like warfarin?
Possibly. Saw Palmetto, Stinging Nettle, Horny Goat Weed, and NAC all carry interactions with blood thinners or antiplatelet drugs — each through different mechanisms. This is important enough to check with your pharmacist or doctor before use.
Is Testaplexx safe to take while pregnant or breastfeeding?
No. DHEA, Tribulus, Maca, Saw Palmetto, Stinging Nettle, Horny Goat Weed, Arimistane, and Bergamot should all be avoided during pregnancy, and most should be avoided while breastfeeding. Talk to your doctor about what's safe for you.
Can Testaplexx help with sexual function?
Several ingredients — DHEA, Tribulus, Tongkat Ali, Maca, and Horny Goat Weed — are marketed for sexual health. DHEA is likely effective for vaginal atrophy in women, Tribulus and Tongkat Ali are possibly effective for sexual function, and the others have insufficient evidence. Results vary by ingredient and person.
Does Testaplexx interact with antibiotics?
Yes. Zinc can reduce the absorption and effectiveness of quinolone antibiotics (like ciprofloxacin), tetracyclines (like doxycycline), and cephalexin. Take these antibiotics at least 2 hours before or 4–6 hours after any zinc supplement.
What are the most common side effects of Testaplexx?
Vitamin D at high doses can raise calcium levels; Zinc may cause nausea, diarrhea, or a metallic taste; DHEA can cause acne and mood changes; Ashwagandha may cause drowsiness; and NAC may cause nausea or heartburn. Most are dose-related and mild at typical amounts, but check the facts for each ingredient if you're sensitive.

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

Not sure if Testaplexx 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.

Testaplexx label
Go deeper

The Full Monographs Behind Testaplexx’s Ingredients

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

Herb & supplement monograph

Vitamin D

Interacts with 715 drugs

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

Read the full Vitamin D monograph → Herb & supplement monograph

Zinc

Interacts with 67 drugs

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

Read the full Zinc monograph → Herb & supplement monograph

Dhea

Interacts with 776 drugs

DHEA is a natural hormone that the body makes and that declines with age, and it is sold as a supplement claiming many benefits. The evidence is mixed and limited for most uses, and because...

Read the full Dhea monograph → Herb & supplement monograph

Maca

Maca is a nutrient-rich Andean root often used for energy, libido, and menopause symptoms. Early studies suggest it may modestly help sexual desire and some menopause symptoms, but the evide...

Read the full Maca monograph → Herb & supplement monograph

Tribulus

Interacts with 259 drugs

Tribulus is a plant supplement most often marketed to boost libido, testosterone, and athletic performance, but the human evidence behind these claims is weak and inconsistent. It is general...

Read the full Tribulus monograph → Herb & supplement monograph

Saw Palmetto

Interacts with 174 drugs

Saw palmetto is a plant extract most often used for urinary symptoms linked to an enlarged prostate (BPH). The best research suggests it works no better than a placebo for most men, though i...

Read the full Saw Palmetto 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

Eurycoma Longifolia

Interacts with 248 drugs

Eurycoma longifolia (tongkat ali) is a Southeast Asian herb most popular for supporting testosterone, libido, and male fertility, with some small human studies suggesting possible benefits....

Read the full Eurycoma Longifolia monograph → Herb & supplement monograph

Stinging Nettle

Interacts with 164 drugs

Stinging nettle is a common plant used as food and in traditional medicine, most often for prostate symptoms, allergies, and joint pain. The evidence is mixed and mostly preliminary, so it i...

Read the full Stinging Nettle monograph → Herb & supplement monograph

N-acetyl Cysteine (nac)

Interacts with 294 drugs

N-acetyl cysteine (NAC) is a supplement form of the amino acid cysteine and a building block for the antioxidant glutathione. It has well-established prescription uses for acetaminophen over...

Read the full N-acetyl Cysteine (nac) monograph → Herb & supplement monograph

Horny Goat Weed

Interacts with 963 drugs

Horny goat weed (Epimedium) is a traditional Chinese herb most often marketed for low libido and erectile problems, but solid human evidence for these uses is lacking. While short-term use s...

Read the full Horny Goat Weed monograph → Herb & supplement monograph

Black Pepper

Interacts with 1,019 drugs

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (li...

Read the full Black Pepper monograph → Herb & supplement monograph

Bergamot

Interacts with 410 drugs

Bergamot is a Mediterranean citrus fruit, and its standardized extract is most often used to support cholesterol and heart health, with some early but promising research. The essential oil i...

Read the full Bergamot monograph → Herb & supplement monograph

Ashwagandha

Interacts with 1,372 drugs

Ashwagandha is an Ayurvedic herb most often taken to help with stress, anxiety, and sleep, and some small studies suggest it may help, though the evidence is still limited. It is generally w...

Read the full Ashwagandha 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

Arimistane

Interacts with 4 drugs

Arimistane (sometimes sold as Estrovade) is a synthetic aromatase inhibitor marketed as a dietary supplement to lower estrogen and raise testosterone, often during or after steroid or prohor...

Read the full Arimistane monograph →
Sources

Sources & How We Checked

Testaplexx'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 531 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 D 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  3. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-7. PubMed
  4. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  5. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialyzed patients taking AI(OH)3. Clin Nephrol 1986;26:146-9.
  6. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  7. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  8. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  9. Moon J. The role of vitamin D in toxic metal absorption. J Am Coll Nutr 1994;13:559-64.
  10. Demontis R, Reissi D, Noel C, et al. Indirect clinical evidence that 1alphaOH vitamin D<SUB>3</SUB> increases the intestinal absorption of aluminum. Clin Nephrol 1989;31:123-7.
  11. Adler AJ, Berlyne GM. Duodenal aluminum absorption in the rat: effect of vitamin D. Am J Physiol 1985;249:G209-13. PubMed
  12. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  13. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  14. Cox KA, Dunn MA. Aluminum toxicity alters the regulation of calbindin-D28k protein and mRNA expression in chick intestine. J Nutr 2001;131:2007-13. PubMed
  15. Escribano, J., Balaguer, A., Pagone, F., Feliu, A., and Roque, I. Figuls. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane.Database.Syst.Rev. 2009;(1):CD004754. PubMed
  16. Carlton, S., Clopton, D., and Cappuzzo, K. A. Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. Consult Pharm 2010;25(3):171-177. PubMed
  17. Wang, H., Xia, N., Yang, Y., and Peng, D. Q. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis. 2012;11:42. PubMed
  18. Turner AN, Carr Reese P, Fields KS, Anderson J, Ervin M, Davis JA, Fichorova RN, Roberts MW, Klebanoff MA, Jackson RD. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis. Am J Obstet G PubMed
  19. Weiner M, Epstein FH. Signs and symptoms of electrolyte disorders. Yale J Biol Med. 1970;43(2):76-109.
  20. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  21. Roth DE, Leung M, Mesfin E, Qamar H, Watterworth J, Papp E. Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ. 2017;359:j5237. PubMed
  22. Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: A randomized clinical trial. JAMA. 2021.
  23. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54-8. PubMed
  24. Doyle D, Browne U, Brickley A, Murphy D. Vitamin D-induced hypercalcaemia and acute kidney injury in sarcoidosis. BMJ Case Rep 2023;16(1):e250580. PubMed
  25. Williamson A, Martineau AR, Sheikh A, Jolliffe D, Griffiths CJ. Vitamin D for the management of asthma. Cochrane Database Syst Rev 2023;2(2):CD011511. PubMed
  26. Kinesya E, Santoso D, Gde Arya N, et al. Vitamin D as adjuvant therapy for diabetic foot ulcers: Systematic review and meta-analysis approach. Clin Nutr ESPEN 2023;54:137-143. PubMed

See these in context on the Vitamin D monograph →

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

See these in context on the Zinc monograph →

Dhea 98 references
  1. Frye RF, Kroboth PD, Folan MM, et al. Effect of DHEA on CYP3A-mediated metabolism of triazolam. Clin Pharmacol Ther 2000;67:109 (abstract PI-82).
  2. Kuritzky L. DHEA: Science or wishful thinking? Hosp Pract 1998;33:85-6. PubMed
  3. Van Vollenhoven RF, Morabito LM, Engleman EG, et al. Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol 1998;25:285-9.
  4. Van Vollenhoven RF, Engleman EG, McGurie JL. Dehydroepiandrosterone in Systemic Lupus Erythematosus. Arth Rheum 1995;38:1826-31. DOI
  5. Ebeling P, Koivisto VA. Physiological importance of dehydroepiandrosterone. Lancet 1994;343:1479-81. PubMed
  6. Yen SS, Morales AJ, Khorram O. Replacement of DHEA in aging men and women. Potential remedial effects. Ann N Y Acad Sci 1995;774:128-42. PubMed
  7. Labrie F, Diamond P, Cusan L, et al. Effect of 12 month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab 1997;82:3498-505. PubMed
  8. Casson PR, Faquin LC, Stentz FB. Replacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in postmenopausal women. (abstract) Fertil Steril 1995;63:1027-31. DOI
  9. Morales AJ, Haubrich RH, Hwang JY, et al. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf)1 PubMed
  10. Arlt W, Justl H, Callies F, et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. [Abstract] J Clin Endocrinol PubMed
  11. Kline MD, Jaggers ED. Mania onset while using dehydroepiandrosterone (letter). Am J Psychiatry 1999;156:971. PubMed
  12. Callies F, Arlt W, Siekmann L, et al. Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females. Steroids 2000;65:98-102. PubMed
  13. Markowitz JS, Carson WH, Jackson CW. Possible dihydroepiandrosterone-induced mania. Biol Psychiatry 1999;45:241-2. PubMed
  14. Stoll BA. Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk. Eur J Clin Nutr 1999;53:771-5. PubMed
  15. Dean CE. Prasterone (DHEA) and mania. Ann Pharmacother 2000;34:1419-22. PubMed
  16. Himmel PB, Seligman TM. A Pilot Study Employing Dehydroepiandrosterone (DHEA) in the Treatment of Chronic Fatigue Syndrome. [Abstract]. J Clin Rheumatol 1999:5:56-9. PubMed
  17. Hunt PJ, Gurnell EM, Huppert FA, et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. J Clin Endocrinol Metab 2000;85:4650-6.. PubMed
  18. Johannsson G, Burman P, Wiren L, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002;87:2046-52. PubMed
  19. Calhoun KE, Pommier RF, Muller P, et al. Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant. Arch Surg 2003;138:879-83.. PubMed
  20. Morris KT, Toth-Fejel S, Schmidt J, et al. High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy. Surgery PubMed
  21. Calhoun K, Pommier R, Cheek J, et al. The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression. Am J Surg 2003;185:411-5.. PubMed
  22. Stomati M, Monteleone P, Casarosa E, et al. Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol Endocrinol 2000;14:342-63.. PubMed
  23. Petri MA, Mease PJ, Merrill JT, et al. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis Rheum 2004;50:2858-68. PubMed
  24. Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf) 2000;53:561-8. PubMed
  25. Acacio BD, Stanczyk FZ, Mullin P, et al. Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men. Fertil Steril 2004;81:595-604. PubMed
  26. Petri MA, Lahita RG, Van Vollenhoven RF, et al. Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2002;46:1820-9. PubMed
  27. Pino JA, Marbot R. Volatile flavor constituents of acerola (Malpighia emarginata DC.) fruit. J Agric Food Chem 2001;49:5880-2.
  28. Nair KS, Rizza RA, O'Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 2006;355:1647-59. PubMed
  29. Alkatib AA, Cosma M, Elamin MB, et al. A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab 2009;94:3676-81. PubMed
  30. Jesse, R. L., Loesser, K., Eich, D. M., Qian, Y. Z., Hess, M. L., Nestler, J. E. Dehydroepiandrosterone inhibits human platelet aggregation in vitro and in vivo. Ann N.Y.Acad Sci 1995;774:281-90.
  31. Bertoni, A., Rastoldo, A., Sarasso, C., Di Vito C., Sampietro, S., Nalin, M., Bagarotti, A., Sinigaglia, F. Dehydroepiandrosterone-sulfate inhibits thrombin-induced platelet aggregation. Steroids 2012;77(3):260-8. PubMed
  32. Cui, Y., Choi, I. S., Koh, Y. A., Lin, X. H., Cho, Y. B., Won, Y. H. Effects of combined BCG and DHEA treatment in preventing the development of asthma. Immunol Invest 2008;37(3):191-202. PubMed
  33. Aisaka, K., Mori, H., Ogawa, T., Kigawa, T. Effects of dehydroepiandrosterone-sulphate (DHEA-S) administration on puerperal lactation and maternal prolactin and estradiol levels. Nippon Sanka Fujinka Gakkai Zasshi 1984;36(10):1935-42.
  34. Lauritzen, C. [Therapeutic attempts with dehydroepiandrosterone sulfate in threatened pregnancies]. Arch Gynakol 1971;211(1):247-9.
  35. Mortola, J. F. Yen, S. S. The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. J Clin Endocrinol Metab 1990;71(3):696-704. PubMed
  36. Rabijewski, M., Zgliczynski, W. [Positive effects of DHEA therapy on insulin resistance and lipids in men with angiographically verified coronary heart disease--preliminary study]. Endokrynol Pol 2005;56(6):904-10.
  37. Weiss, E. P., Shah, K., Fontana, L., Lambert, C. P., Holloszy, J. O., Villareal, D. T. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am J Clin Nutr 2009;89(5):1459-67. PubMed
  38. Jankowski, C. M., Gozansky, W. S., Kittelson, J. M., Van Pelt, R. E., Schwartz, R. S., Kohrt, W. M. Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens. J Clin E PubMed
  39. Poretsky, L., Song, L., Brillon, D. J., Ferrando, S., Chiu, J., McElhiney, M., Ferenczi, A., Sison, C., Haller, I., Rabkin, J. Metabolic and hormonal effects of oral DHEA in premenopausal women with HIV infection: a randomized, prospective, placebo-contro
  40. Libe, R., Barbetta, L., Dall'Asta, C., Salvaggio, F., Gala, C., Beck-Peccoz, P., Ambrosi, B. Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism. J Endocrinol Invest 2004;27 PubMed
  41. Genazzani, A. R., Inglese, S., Lombardi, I., Pieri, M., Bernardi, F., Genazzani, A. D., Rovati, L., Luisi, M. Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. Aging Male 2004;7(2):133-43. PubMed
  42. von Muhlen D., Laughlin, G. A., Kritz-Silverstein, D., Bergstrom, J., Bettencourt, R. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int 2008;19(5):
  43. Kritz-Silverstein, D., von, Muhlen D., Laughlin, G. A., Bettencourt, R. Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: the DHEA and Well-Ness (DAWN) Trial. J Am Geriatr Soc 2008;56(7):1292-8. PubMed
  44. Penisson-Besnier, I., Devillers, M., Porcher, R., Orlikowski, D., Doppler, V., Desnuelle, C., Ferrer, X., Bes, M. C., Bouhour, F., Tranchant, C., Lagrange, E., Vershueren, A., Uzenot, D., Cintas, P., Sole, G., Hogrel, J. Y., Laforet, P., Vial, C., Vila, A
  45. Casson, P. R., Santoro, N., Elkind-Hirsch, K., Carson, S. A., Hornsby, P. J., Abraham, G., Buster, J. E. Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high-density lipoprotein: a six-month t
  46. Araneo, B. Daynes, R. Dehydroepiandrosterone functions as more than an antiglucocorticoid in preserving immunocompetence after thermal injury. Endocrinology 1995;136(2):393-401. PubMed
  47. Nordmark, G., Bengtsson, C., Larsson, A., Karlsson, F. A., Sturfelt, G., Ronnblom, L. Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus. Autoimmunity PubMed
  48. Srinivasan, M., Irving, B. A., Frye, R. L., O'Brien, P., Hartman, S. J., McConnell, J. P., Nair, K. S. Effects on lipoprotein particles of long-term dehydroepiandrosterone in elderly men and women and testosterone in elderly men. J Clin Endocrinol Metab 2 PubMed
  49. Srinivasan, M., Irving, B. A., Dhatariya, K., Klaus, K. A., Hartman, S. J., McConnell, J. P., Nair, K. S. Effect of dehydroepiandrosterone replacement on lipoprotein profile in hypoadrenal women. J Clin Endocrinol Metab 2009;94(3):761-4. PubMed
  50. Jankowski, C. M., Gozansky, W. S., Van Pelt, R. E., Wolfe, P., Schwartz, R. S., Kohrt, W. M. Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids. Clin Endocrinol (Oxf) 2011;75(4):456-6 PubMed
  51. McHenry, C. M., Bell, P. M., Hunter, S. J., Thompson, C. J., Courtney, C. H., Ennis, C. N., Sheridan, B., McCance, D. R., Mullan, K. R., Atkinson, A. B. Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life i
  52. Jankowski, C. M., Gozansky, W. S., Schwartz, R. S., Dahl, D. J., Kittelson, J. M., Scott, S. M., Van Pelt, R. E., Kohrt, W. M. Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial. J PubMed
  53. Forsblad-d'Elia, H., Carlsten, H., Labrie, F., Konttinen, Y. T., Ohlsson, C. Low serum levels of sex steroids are associated with disease characteristics in primary Sjogren's syndrome; supplementation with dehydroepiandrosterone restores the concentration
  54. Finckh, A., Berner, I. C., Aubry-Rozier, B., So, A. K. A randomized controlled trial of dehydroepiandrosterone in postmenopausal women with fibromyalgia. J Rheumatol 2005;32(7):1336-40.
  55. Gebre-Medhin, G., Husebye, E. S., Mallmin, H., Helstrom, L., Berne, C., Karlsson, F. A., Kampe, O. Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease. Clin Endocrinol (Oxf) 2000;52(6):775-80. PubMed
  56. Lovas, K., Gebre-Medhin, G., Trovik, T. S., Fougner, K. J., Uhlving, S., Nedrebo, B. G., Myking, O. L., Kampe, O., Husebye, E. S. Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month,
  57. Pillemer, S. R., Brennan, M. T., Sankar, V., Leakan, R. A., Smith, J. A., Grisius, M., Ligier, S., Radfar, L., Kok, M. R., Kingman, A., Fox, P. C. Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjogren's syndrome. Arthritis Rheum
  58. Christiansen, J. J., Andersen, N. H., Sorensen, K. E., Pedersen, E. M., Bennett, P., Andersen, M., Christiansen, J. S., Jorgensen, J. O., Gravholt, C. H. Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and
  59. Panjari, M., Bell, R. J., Jane, F., Wolfe, R., Adams, J., Morrow, C., Davis, S. R. A randomized trial of oral DHEA treatment for sexual function, well-being, and menopausal symptoms in postmenopausal women with low libido. J Sex Med 2009;6(9):2579-90. PubMed
  60. Mamas, L., Mamas, E. Dehydroepiandrosterone supplementation in assisted reproduction: rationale and results. Curr Opin Obstet Gynecol 2009;21(4):306-8. PubMed
  61. Hartkamp, A., Geenen, R., Godaert, G. L., Bootsma, H., Kruize, A. A., Bijlsma, J. W., Derksen, R. H. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren syndrome: a randomised controlled tr
  62. Yeung, T. W., Li, R. H., Lee, V. C., Ho, P. C., Ng, E. H. A randomized double-blinded placebo-controlled trial on the effect of dehydroepiandrosterone for 16 weeks on ovarian response markers in women with primary ovarian insufficiency. J Clin Endocrinol PubMed
  63. Virkki, L. M., Porola, P., Forsblad-d'Elia, H., Valtysdottir, S., Solovieva, S. A., Konttinen, Y. T. Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjogren's syndrome. Arthritis Care Res (Ho
  64. Binder, G., Weber, S., Ehrismann, M., Zaiser, N., Meisner, C., Ranke, M. B., Maier, L., Wudy, S. A., Hartmann, M. F., Heinrich, U., Bettendorf, M., Doerr, H. G., Pfaeffle, R. W., Keller, E. Effects of dehydroepiandrosterone therapy on pubic hair growth an
  65. Klove, K. L., Roy, S., Lobo, R. A. The effect of different contraceptive treatments on the serum concentration of dehydroepiandrosterone sulfate. Contraception 1984;29(4):319-24. PubMed
  66. Cibula, D., Fanta, M., Vrbikova, J., Stanicka, S., Dvorakova, K., Hill, M., Skrha, J., Zivny, J., Skrenkova, J. The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogena
  67. White, T., Jain, J. K., Stanczyk, F. Z. Effect of oral versus transdermal steroidal contraceptives on androgenic markers. Am J Obstet Gynecol 2005;192(6):2055-9. PubMed
  68. Vacheron-Trystram, M. N., Cheref, S., Gauillard, J., Plas, J. [A case report of mania precipitated by use of DHEA]. Encephale 2002;28(6 Pt 1):563-6.
  69. Gurnell, E. M., Hunt, P. J., Curran, S. E., Conway, C. L., Pullenayegum, E. M., Huppert, F. A., Compston, J. E., Herbert, J., Chatterjee, V. K. Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial. J Clin Endocrinol PubMed
  70. Christiansen, J. J., Bruun, J. M., Christiansen, J. S., Jorgensen, J. O., Gravholt, C. H. Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial. Eur J Endocrinol 2011;165(2 PubMed
  71. Bloch, M., Ish-Shalom, S., Greenman, Y., Klein, E., Latzer, Y. Dehydroepiandrosterone treatment effects on weight, bone density, bone metabolism and mood in women suffering from anorexia nervosa-a pilot study. Psychiatry Res 2012;200(2-3):544-9. PubMed
  72. Merritt, P., Stangl, B., Hirshman, E., Verbalis, J. Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women. Brain Res 11-5-2012;1483:54-62. PubMed
  73. Stangl, B., Hirshman, E., and Verbalis, J. Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial performance in postmenopausal women. Behav Neurosci 2011;125(5):742-52. PubMed
  74. Artini, P. G., Simi, G., Ruggiero, M., Pinelli, S., Di Berardino, O. M., Papini, F., Papini, S., Monteleone, P., Cela, V. DHEA supplementation improves follicular microenviroment in poor responder patients. Gynecol Endocrinol 2012;28(9):669-73. PubMed
  75. Genazzani, A. R., Stomati, M., Valentino, V., Pluchino, N., Pot, E., Casarosa, E., Merlini, S., Giannini, A., Luisi, M. Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality. Climacteric 2011;14(6):661-8. PubMed
  76. Dayal, M., Sammel, M. D., Zhao, J., Hummel, A. C., Vandenbourne, K., Barnhart, K. T. Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids. J Womens Health (Larchmt) 2005;14(5):391-400. PubMed
  77. Vogiatzi, M. G., Boeck, M. A., Vlachopapadopoulou, E., el-Rashid, R., New, M. I. Dehydroepiandrosterone in morbidly obese adolescents: effects on weight, body composition, lipids, and insulin resistance. Metabolism 1996;45(8):1011-5. PubMed
  78. Bernardi, F., Pieri, M., Stomati, M., Luisi, S., Palumbo, M., Pluchino, N., Ceccarelli, C., Genazzani, A. R. Effect of different hormonal replacement therapies on circulating allopregnanolone and dehydroepiandrosterone levels in postmenopausal women. Gyne DOI
  79. Schlegel, W., Petersdorf, L. I., Junker, R., Schulte, H., Ebert, C., Von Eckardstein, A. The effects of six months of treatment with a low-dose of conjugated oestrogens in menopausal women. Clin Endocrinol (Oxf) 1999;51(5):643-51. PubMed
  80. Rao, M. S., Subbarao, V., Yeldandi, A. V., and Reddy, J. K. Hepatocarcinogenicity of dehydroepiandrosterone in the rat. Cancer Res. 5-15-1992;52(10):2977-2979.
  81. Tagliaferro, A. R., Roebuck, B. D., Ronan, A. M., and Meeker, L. D. Enhancement of pancreatic carcinogenesis by dehydroepiandrosterone. Adv.Exp.Med Biol. 1992;322:119-129. PubMed
  82. Buster, J. E., Casson, P. R., Straughn, A. B., Dale, D., Umstot, E. S., Chiamori, N., and Abraham, G. E. Postmenopausal steroid replacement with micronized dehydroepiandrosterone: preliminary oral bioavailability and dose proportionality studies. Am J Ob
  83. Kocis, P. Prasterone. Am J Health Syst.Pharm. 11-15-2006;63(22):2201-2210.
  84. Karp, G., Bentov, Y., Masalha, R., and Ifergane, G. Onset of late posttraumatic seizure after dehydroepiandrosterone treatment. Fertil.Steril. 2009;91(3):931-932. PubMed
  85. Stanczyk, F. Z., Slater, C. C., Ramos, D. E., Azen, C., Cherala, G., Hakala, C., Abraham, G., and Roy, S. Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term oral dehydroepiandrosterone treatment in postmenopausal women. Menopa PubMed
  86. Rice, S. P., Agarwal, N., Bolusani, H., Newcombe, R., Scanlon, M. F., Ludgate, M., and Rees, D. A. Effects of dehydroepiandrosterone replacement on vascular function in primary and secondary adrenal insufficiency: a randomized crossover trial. J Clin End PubMed
  87. Mizokami, A., Koh, E., Izumi, K., Narimoto, K., Takeda, M., Honma, S., Dai, J., Keller, E. T., and Namiki, M. Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of testosterone and dihydrotestoster
  88. Liu, X., Arnold, J. T., and Blackman, M. R. Dehydroepiandrosterone administration or G{alpha}q overexpression induces {beta}-catenin/T-Cell factor signaling and growth via increasing association of estrogen receptor-{beta}/Dishevelled2 in androgen-indepe
  89. El-Alfy, M., Deloche, C., Azzi, L., Bernard, B. A., Bernerd, F., Coutet, J., Chaussade, V., Martel, C., Leclaire, J., and Labrie, F. Skin responses to topical dehydroepiandrosterone: implications in antiageing treatment? Br.J Dermatol. 2010;163(5):968-97 PubMed
  90. Chen, M. J., Chen, C. D., Yang, J. H., Chen, C. L., Ho, H. N., Yang, W. S., and Yang, Y. S. High serum dehydroepiandrosterone sulfate is associated with phenotypic acne and a reduced risk of abdominal obesity in women with polycystic ovary syndrome. Hum. PubMed
  91. Goldberg, M. Dehydroepiandrosterone, insulin-like growth factor-I, and prostate cancer. Ann Intern Med 10-1-1998;129(7):587-588. PubMed
  92. Sahelian, R. and Borken, S. Dehydroepiandrosterone and cardiac arrhythmia. Ann Intern.Med 10-1-1998;129(7):588. PubMed
  93. Liao YH, Liao KF, Kao CL, et al. Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage. Eur J Appl Physiol 2013;113(1):99-107. PubMed
  94. Yeung TW, Chai J, Li RH, et al. A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders. Fertil Steril 2014;102(1):108-115.e1. PubMed
  95. Buisson C, Frelat C, Privat K, Martinat N, Audran M, Collomp K. Metabolic and isotopic signature of short-term DHEA administration in women: Comparison with findings in men. Drug Test Anal. 2018;10(11-12):1744-1754. PubMed
  96. Gravisse N, Vibarel-Rebot N, Labsy Z, et al. Short-term dehydroepiandrosterone intake and supramaximal exercise in young recreationally-trained women. Int J Sports Med. 2018;39(9):712-719. PubMed
  97. Chen SN, Tsui KH, Wang PH, Chern CU, Wen ZH, Lin LT. Dehydroepiandrosterone supplementation improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve. Front Endocrinol (Lausanne). 2019;10:800. PubMed
  98. Li Y, Ren J, Li N, et al. A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials. Exp Gerontol 2020;141:111110. Online ahead of print. PubMed

See these in context on the Dhea monograph →

Maca 1 reference
  1. Valerio, L. G., Jr. and Gonzales, G. F. Toxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii) : a critical synopsis. Toxicol.Rev 2005;24(1):11-35. PubMed

See these in context on the Maca monograph →

Tribulus 10 references
  1. Sharifi AM, Darabi R, Akbarloo N. Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity. Life Sci 2003;73:2963-71. PubMed
  2. Walker D, Bird A, Flora T, O'Sullivan B. Some effects of feeding Tribulus terrestris, Ipomoea lonchophylla and the seed of Abelmoschus ficulneus on fetal development and the outcome of pregnancy in sheep. Reprod Fertil Dev 1992;4:135-44. PubMed
  3. Al-Ali M, Wahbi S, Twaij H, Al-Badr A. Tribulus terrestris: preliminary study of its diuretic and contractile effects and comparison with Zea mays. J Ethnopharmacol 2003;85:257-60. PubMed
  4. Tabakova, P., Dimitrov, M., Ognyanov, K., and et al. Clinical study of Tribestan in females with endocrine sterility. Documentation for Registration (unpublished) 1999.
  5. Akhtari E, Raisi F, Keshavarz M, et al. Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo-controlled study. Daru 2014;22:40. PubMed
  6. Ryan M, Lazar I, Nadasdy GM, et al. Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris. Clin Nephrol 2015;83(3):177-83. PubMed
  7. Postigo S, Lima SM, Yamada SS, et al. Assessment of the effects of Tribulus terrestris on sexual function of menopausal women. Rev Bras Ginecol Obstet 2016;38(3):140-6. PubMed
  8. Talasaz AH, Abbasi MR, Abkhiz S, Dashti-Khavidaki S. Tribulus terrestris-induced severe nephrotoxicity in a young healthy male. Nephrol Dial Tranplant 2010;25(11):3792-3. PubMed
  9. Samani NB, Jokar A, Soveid M, Heydari M, Mosavat SH. Efficacy of the hydroalcoholic extract of Tribulus terrestris on the serum glucose and lipid profile of women with diabetes mellitus: a double-blind randomized placebo-controlled clinical trial. J Evid
  10. Siddiqui MA, Itrat M, Mobeen A, Khan MI. Efficacy of khar-i-khasak (Tribulus terrestris Linn.) in prehypertension: a randomized, double-blind, placebo-controlled trial. J Complement Integr Med. 2021.

See these in context on the Tribulus monograph →

Saw Palmetto 22 references
  1. Wilt TJ, Ishani A, Stark G, et al. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA 1998;280:1604-9. PubMed
  2. Carraro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate 1996;29:231-40. DOI
  3. Di Silverio F, D'Eramo G, Lubrano C, et al. Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. Eur Urol 1992;21:309-14. PubMed
  4. Stepanov VN, Siniakova LA, Sarrazin B, Raynaud JP. Efficacy and tolerability of the lipidosterolic extract of Serenoa repens (Permixon) in benign prostatic hyperplasia: a double-blind comparison of two dosage regimens. Adv Ther 1999;16:231-41.
  5. Cheema P, El-Mefty O, Jazieh AR. Intraoperative haemorrhage associated with the use of extract of Saw Palmetto herb: a case report and review of literature. J Intern Med 2001;250:167-9. PubMed
  6. Jibrin I, Erinle A, Saidi A, Aliyu ZY. Saw palmetto-induced pancreatitis. South Med J 2006;99:611-2. PubMed
  7. Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. J Altern Complement Med 2002
  8. Avins AL, Bent S, Staccone S, et al. A detailed safety assessment of a saw palmetto extract. Complement Ther Med 2008;16:147-54. PubMed
  9. Morgia, G., Mucciardi, G., Gali, A., Madonia, M., Marchese, F., Di, Benedetto A., Romano, G., Bonvissuto, G., Castelli, T., Macchione, L., and Magno, C. Treatment of chronic prostatitis/chronic pelvic pain syndrome category IIIA with Serenoa repens plus
  10. Aliaev, IuG, Vinarov, A. Z., Lokshin, K. L., and Spivak, L. G. [Efficiency and safety of prostamol-Uno in patients with chronic abacterial prostatitis]. Urologiia. 2006;(1):47-50.
  11. Agbabiaka, T. B., Pittler, M. H., Wider, B., and Ernst, E. Serenoa repens (saw palmetto): a systematic review of adverse events. Drug Saf 2009;32(8):637-647. PubMed
  12. Wargo, K. A., Allman, E., and Ibrahim, F. A possible case of saw palmetto-induced pancreatitis. South.Med.J. 2010;103(7):683-685. PubMed
  13. Lapi, F., Gallo, E., Giocaliere, E., Vietri, M., Baronti, R., Pieraccini, G., Tafi, A., Menniti-Ippolito, F., Mugelli, A., Firenzuoli, F., and Vannacci, A. Acute liver damage due to Serenoa repens: a case report. Br.J.Clin.Pharmacol. 2010;69(5):558-560.
  14. Mantovani, F. Serenoa repens in benign prostatic hypertrophy: analysis of 2 Italian studies. Minerva Urol.Nefrol. 2010;62(4):335-340.
  15. Hanaka, M., Yoshii, C., Yatera, K., Ito, C., Chojin, Y., Nagata, S., Yamasaki, K., Nishida, C., Kawanami, T., Kawanami, Y., Ishimoto, H., and Mukae, H. [A case of rhabdomyolysis caused by saw palmetto of healthy foods]. J.UOEH. 6-1-2012;34(2):193-199. PubMed
  16. Miroddi, M., Carni, A., Mannucci, C., Moleti, M., Navarra, M., and Calapai, G. Hot flashes in a young girl: a wake-up call concerning Serenoa repens use in children. Pediatrics 2012;130(5):e1374-e1376.
  17. Braeckman J. The extract of Serenoa repens in the treatment of benign prostatic hyperplasia: a multicenter open study. Current Therapeutic Research 1994;55(7):776-785. DOI
  18. Jipescu D, Patel A, Bohra H, Pientka A. Rare case of saw palmetto induced heart block. JACC 2017;69(11) supplement:2310.
  19. Morabito P, Miroddi M, Giovinazzo S, Spina E, Calapai G. Serenoa repens as an endocrine disruptor in a 10-year-Old young girl: a new case report. Pharmacology. 2015;96(1-2):41-3. doi: 10.1159/000431327.
  20. Gammoudi R, Ameur K, Ouni B, et al. Fixed drug eruption to Serenoa repens: first case report and consideration of the use of herbal medicine. Dermatol Ther 2020 Aug 29:e14247.
  21. Paulis G, Paulis A, Perletti G. Serenoa repens and its effects on male sexual function. A systematic review and meta-analysis of clinical trials. Arch Ital Urol Androl 2021;93(4):475-480. PubMed
  22. Venkateswaran S, Declet-Bauzo R, Shodeinde M, Gilford P. Postoperative Retroperitoneal Hematoma: A Case of Saw Palmetto and the Importance of Primary Care Intervention. HCA Healthc J Med 2020;1(5):279-282. PubMed

See these in context on the Saw Palmetto 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 →

Eurycoma Longifolia 4 references
  1. Salman SA, Amrah S, Wahab MS, et al. Modification of propranolol's bioavailability by Eurycoma longifolia water-based extract. J Clin Pharm Ther 2010;35:691-6. PubMed
  2. Tambi MI, Imran MK, Henkel RR. Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism? Andrologia 2011 Jun 15. doi: 10.1111/j.1439-0272.2011.01168.x. [Epub ahead of pri PubMed
  3. Han YM, Kim IS, Rehman SU, Choe K, Yoo HH. In vitro evaluation of the effects of Eurycoma longifolia extract on CYP-mediated drug metabolism. Evid Based Complement Alternat Med 2015;2015:631329.
  4. Chinnappan SM, George A, Pandey P, Narke G, Choudhary YK. Effect of Eurycoma longifolia standardised aqueous root extract-Physta ® on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicent

See these in context on the Eurycoma Longifolia monograph →

Stinging Nettle 23 references
  1. Monographs on the medicinal uses of plant drugs. Exeter, UK: European Scientific Co-op Phytother, 1997.
  2. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  3. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  4. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician's Guide to Herbal Medicine. Terry C. Telger, transl. 3rd ed. Berlin, GER: Springer, 1998.
  5. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  6. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  7. Mittman P. Randomized, double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis. Planta Med 1990;56:44-7.
  8. Vontobel HP, Herzog R, Rutishauser G, Kres H. [Results of a double-blind study on the effectiveness of ERU (extractum radicis Urticae) capsules in conservative treatment of benign prostatic hyperplasia]. (Abstract). Urologe A 1985;24:49-51.
  9. Randall C, Randall H, Dobbs F, et al. Randomized controlled trial of nettle sting for treatment of base-of-thumb pain. J R Soc Med 2000;93:305-9. PubMed
  10. Caliskaner Z, Karaayvaz M, Ozturk S. Misuse of a herb: stinging nettle (Urtica urens) induced severe tongue oedema. Complement Ther Med 2004;12:57-8. PubMed
  11. Krzeski, T., Kazon, M., Borkowski, A., Witeska, A., and Kuczera, J. Combined extracts of Urtica dioica and Pygeum africanum in the treatment of benign prostatic hyperplasia: double-blind comparison of two doses. Clin Ther 1993;15(6):1011-1020.
  12. Randall, C., Meethan, K., Randall, H., and Dobbs, F. Nettle sting of Urtica dioica for joint pain--an exploratory study of this complementary therapy. Complement Ther Med 1999;7(3):126-131. PubMed
  13. Tahri, A., Yamani, S., Legssyer, A., Aziz, M., Mekhfi, H., Bnouham, M., and Ziyyat, A. Acute diuretic, natriuretic and hypotensive effects of a continuous perfusion of aqueous extract of Urtica dioica in the rat. J Ethnopharmacol 2000;73(1-2):95-100. PubMed
  14. Sahin, M., Yilmaz, H., Gursoy, A., Demirel, A. N., Tutuncu, N. B., and Guvener, N. D. Gynaecomastia in a man and hyperoestrogenism in a woman due to ingestion of nettle (Urtica dioica). N.Z.Med.J. 2007;120(1265):U2803.
  15. Randall, C., Dickens, A., White, A., Sanders, H., Fox, M., and Campbell, J. Nettle sting for chronic knee pain: a randomised controlled pilot study. Complement Ther.Med. 2008;16(2):66-72. PubMed
  16. Rayburn, K., Fleischbein, E., Song, J., Allen, B., Kundert, M., Leiter, C., and Bush, T. Stinging nettle cream for osteoarthritis. Altern.Ther.Health Med. 2009;15(4):60-61.
  17. Oliver, F., Amon, E. U., Breathnach, A., Francis, D. M., Sarathchandra, P., Black, A. K., and Greaves, M. W. Contact urticaria due to the common stinging nettle (Urtica dioica)-- histological, ultrastructural and pharmacological studies. Clin Exp Dermato PubMed
  18. Kulze, A. and Greaves, M. Contact urticaria caused by stinging nettles. Br.J Dermatol. 1988;119(2):269-270. PubMed
  19. Patten G. Medicinal plant review: Urtica. Aust J Med Herbalism 1993;5(1):5-13.
  20. Maor D, Little M. Skin contact with a stinging tree requiring intensive care unit admission. Contact Dermatitis. 2017 Nov;77(5):335-37. PubMed
  21. Easton L, Vaid S, Nagel AK, Venci JV, Fortuna RJ. Stinging Nettle (Urtica dioica): An Unusual Case of Galactorrhea. Am J Case Rep 2021;22:e933999. PubMed
  22. Niazi B, Ahmed K, Ahmed M, Ali S, Song K, Elias S. Drug-Induced Liver Injury from Herbal Liver Detoxification Tea. Case Rep Gastroenterol 2022;16(3):612-617. PubMed
  23. Nnamani I, Tolu-Akinnawo O, Dufera RR, Akintunde A, Maliakkal B. Tinospora cordifolia (Guduchi/Giloy)-Induced Liver Injury: A Case Review. Cureus 2023;15(5):e39793. PubMed

See these in context on the Stinging Nettle monograph →

N-acetyl Cysteine (nac) 86 references
  1. Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
  2. Jepsen S, Hansen AB. The influence of N-acetylcysteine on the measurement of prothrombin time and activated partial thromboplastin time in healthy subjects. Scand J Clin Lab Invest 1994;54:543-7. PubMed
  3. van Zandwijk N, Dalesio O, Pastorino U, et al. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the European Organization for Research and Treatment of Cancer Head and Neck and Lung C DOI
  4. Horowitz RS, Dart RC, Jarvie DR, et al. Placental transfer of N-acetylcysteine following human maternal acetaminophen toxicity. J Toxicol Clin Toxicol 1997;35:447-51.
  5. Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med 1998;31:710-5. PubMed
  6. Spiller HA, Krenzelok EP, Grande GA, et al. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. Ann Emerg Med 1994;23:519-23. PubMed
  7. Ardissino D, Merlini PA, Savonitto S, et al. Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol 1997;29:941-7. PubMed
  8. Horowitz JD, Henry CA, Syrjanen ML, et al. Nitroglycerine/N-acetylcysteine in the management of unstable angina pectoris. Eur Heart J 1988;9:95-100. PubMed
  9. Louwerse ES, Weverling GJ, Bossuyt PM, et al. Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch Neurol 1995;52:559-64. PubMed
  10. Wiklund O, Fager G, Andersson A, et al. N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels. Atherosclerosis 1996;119:99-106. PubMed
  11. De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J 1997;10:1535-41. PubMed
  12. Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. Clin Pharmacol Ther 1992;52:125-33. PubMed
  13. Behr J, Maier K, Degenkolb B, et al. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression. Am J Respir Crit Care Med 1997;156:1897-901.
  14. Tenenbein PK, Sitar DS, Tenenbein M. Interaction between N-acetylcysteine and activated charcoal: implications for the treatment of acetaminophen poisoning. Pharmacotherapy 2001;21:1331-6.
  15. Arstall MA, Yang J, Stafford I, et al. N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects. Circulation 1995;92:2855-62.
  16. Estensen RD, Levy M, Klopp SJ, et al. N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps. Cancer Lett 1999;147:109-14. PubMed
  17. Pela R, Calcagni AM, Subiaco S, et al. N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD. Respiration 1999;66:495-500.. PubMed
  18. Oldemeyer JB, Biddle WP, Wurdeman RL, et al. Acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography. Am Heart J 2003;146:E23. . PubMed
  19. Ekins BR, Ford DC, Thompson MI, et al. The effect of activated charcoal on N-acetylcysteine absorption in normal subjects. Am J Emerg Med. 1987;5(6):483-7. PubMed
  20. Chamberlain JM, Gorman RL, Oderda GM, Klein-Schwartz W, Klein BL. Use of activated charcoal in a simulated poisoning with acetaminophen: a new loading dose for N-acetylcysteine? Ann Emerg Med. 1993;22(9):1398-402. PubMed
  21. Renzi FP, Donovan JW, Martin TG, Morgan L, Harrison EF. Concomitant use of activated charcoal and N-acetylcysteine. Ann Emerg Med. 1985;14(6):568-72. DOI
  22. North DS, Peterson RG, Krenzelok EP. Effect of activated charcoal administration on acetylcysteine serum levels in humans. Am J Hosp Pharm. 1981;38(7):1022-4. DOI
  23. Loscalzo J. N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin. J Clin Invest. 1985;76(2):703-8. PubMed
  24. Ruiz FJ, Salom MG, Inglés AC, et al. N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs. Am J Physiol. 1994;267(3 Pt 2):R767-72. PubMed
  25. Deharo E, Barkan D, Krugliak M, Golenser J, Ginsburg H. Potentiation of the antimalarial action of chloroquine in rodent malaria by drugs known to reduce cellular glutathione levels. Biochem Pharmacol. 2003;66(5):809-17. PubMed
  26. Buckley, N. A., Whyte, I. M., O'Connell, D. L., and Dawson, A. H. Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning? J Toxicol.Clin Toxicol. 1999;37(6):759-767.
  27. Sunman, W., Hughes, A. D., and Sever, P. S. Anaphylactoid response to intravenous acetylcysteine. Lancet 5-16-1992;339(8803):1231-1232. PubMed
  28. Reynard, K., Riley, A., and Walker, B. E. Respiratory arrest after N-acetylcysteine for paracetamol overdose. Lancet 9-12-1992;340(8820):675. PubMed
  29. BERNSTEIN, I. L. and AUSDENMOORE, R. W. IATROGENIC BRONCHOSPASM OCCURRING DURING CLINICAL TRIALS OF A NEW MUCOLYTIC AGENT, ACETYLCYSTEINE. Dis.Chest 1964;46:469-473. PubMed
  30. REAS, H. W. THE USE OF N-ACETYLCYSTEINE IN THE TREATMENT OF CYSTIC FIBROSIS. J Pediatr 1964;65:542-557. PubMed
  31. Bibi, H., Seifert, B., Oullette, M., and Belik, J. Intratracheal N-acetylcysteine use in infants with chronic lung disease. Acta Paediatr. 1992;81(4):335-339. PubMed
  32. Jepsen, S., Herlevsen, P., Knudsen, P., Bud, M. I., and Klausen, N. O. Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study. Crit Care Med 1992;20(7):918-923. PubMed
  33. Roes, E. M., Raijmakers, M. T., Boo, T. M., Zusterzeel, P. L., Merkus, H. M., Peters, W. H., and Steegers, E. A. Oral N-acetylcysteine administration does not stabilise the process of established severe preeclampsia. Eur.J Obstet.Gynecol.Reprod.Biol 2006
  34. Spiller, H. A., Winter, M. L., Klein-Schwartz, W., and Bangh, S. A. Efficacy of activated charcoal administered more than four hours after acetaminophen overdose. J Emerg.Med 2006;30(1):1-5. PubMed
  35. Tirouvanziam, R., Conrad, C. K., Bottiglieri, T., Herzenberg, L. A., Moss, R. B., and Herzenberg, L. A. High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl.Acad.Sci U.S.A 3-21-2006;103(12):4628-463
  36. Niemi, T. T., Munsterhjelm, E., Poyhia, R., Hynninen, M. S., and Salmenpera, M. T. The effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm. Blood Coagul.Fibrinolysis 2006;1 PubMed
  37. Komisarof, J. A., Gilkey, G. M., Peters, D. M., Koudelka, C. W., Meyer, M. M., and Smith, S. M. N-acetylcysteine for patients with prolonged hypotension as prophylaxis for acute renal failure (NEPHRON). Crit Care Med 2007;35(2):435-441. PubMed
  38. Grimble, G. K. Adverse gastrointestinal effects of arginine and related amino acids. J Nutr 2007;137(6 Suppl 2):1693S-1701S. PubMed
  39. Berk, M., Copolov, D. L., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., and Bush, A. I. N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial. Biol Psychiatry 9-15-2008;64(6) PubMed
  40. Shahin, A. Y., Hassanin, I. M., Ismail, A. M., Kruessel, J. S., and Hirchenhain, J. Effect of oral N-acetyl cysteine on recurrent preterm labor following treatment for bacterial vaginosis. Int J Gynaecol.Obstet. 2009;104(1):44-48. PubMed
  41. Nigwekar, S. U. and Kandula, P. N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta-analysis. Ann Thorac.Surg 2009;87(1):139-147. PubMed
  42. Sandilands, E. A. and Bateman, D. N. Adverse reactions associated with acetylcysteine. Clin Toxicol.(Phila) 2009;47(2):81-88. PubMed
  43. Wijeysundera, D. N., Karkouti, K., Rao, V., Granton, J. T., Chan, C. T., Raban, R., Carroll, J., Poonawala, H., and Beattie, W. S. N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery. Crit Care Me PubMed
  44. Holdiness, M. R. Clinical pharmacokinetics of N-acetylcysteine. Clin Pharmacokinet. 1991;20(2):123-134. PubMed
  45. Dawson, A. H., Henry, D. A., and McEwen, J. Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning. Med J Aust. 3-20-1989;150(6):329-331.
  46. Rasmussen, J. B. and Glennow, C. Reduction in days of illness after long-term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis. Eur.Respir.J 1988;1(4):351-355. DOI
  47. Walters, M. T., Rubin, C. E., Keightley, S. J., Ward, C. D., and Cawley, M. I. A double-blind, cross-over, study of oral N-acetylcysteine in Sjogren's syndrome. Scand J Rheumatol.Suppl 1986;61:253-258.
  48. Cato, A., Goldstein, I., and Millman, M. A double-blind parallel study of acetylcysteine-isoproterenol and saline-isoproterenol in patients with chronic obstructive lung disease. J Int Med Res 1977;5(3):175-183. PubMed
  49. Parr, G. D. and Huitson, A. Oral Fabrol (oral N-acetyl-cysteine) in chronic bronchitis. Br.J.Dis.Chest 1987;81(4):341-348.
  50. Dano, G. Bronchospasm caused by acetylcysteine in children with bronchial asthma. Acta Allergol. 1971;26(3):181-190. DOI
  51. Howatt, W. F. and DeMuth, G. R. A double-blind study of the use of acetylcysteine in patients with cystic fibrosis. Univ Mich.Med Cent.J 1966;32(2):82-85.
  52. Millman, M. and Grundon, W. Use of acetylcysteine in bronchial asthma and emphysema. J Asthma Res 1969;6(4):199-209. PubMed
  53. Vale, J. A. and Wheeler, D. C. Anaphylactoid reaction to acetylcysteine. Lancet 10-30-1982;2(8305):988.
  54. Mant, T. G., Tempowski, J. H., Volans, G. N., and Talbot, J. C. Adverse reactions to acetylcysteine and effects of overdose. Br Med J (Clin Res Ed) 7-28-1984;289(6439):217-219. PubMed
  55. Myers, C., Bonow, R., Palmeri, S., Jenkins, J., Corden, B., Locker, G., Doroshow, J., and Epstein, S. A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine. Semin.Oncol 1983;10(1 Suppl 1):53-55.
  56. Miller, L. F. and Rumack, B. H. Clinical safety of high oral doses of acetylcysteine. Semin.Oncol 1983;10(1 Suppl 1):76-85.
  57. Boman, G., Backer, U., Larsson, S., Melander, B., and Wahlander, L. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir.Dis 1983;64(6):405-415.
  58. Tattersall, A. B., Bridgman, K. M., and Huitson, A. Irish general practice study of acetylcysteine (Fabrol) in chronic bronchitis. J Int Med Res 1984;12(2):96-101. PubMed
  59. Jackson, I. M., Barnes, J., and Cooksey, P. Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: a double-blind placebo controlled study. J Int Med Res 1984;12(3):198-206. PubMed
  60. Ho, S. W. and Beilin, L. J. Asthma associated with N-acetylcysteine infusion and paracetamol poisoning: report of two cases. Br Med J (Clin Res Ed) 9-24-1983;287(6396):876-877. PubMed
  61. Vale, J. A. and Buckley, B. M. Asthma associated with N-acetylcysteine infusion and paracetamol poisoning. Br Med J (Clin Res Ed) 10-22-1983;287(6400):1223. PubMed
  62. Bateman, D. N., Woodhouse, K. W., and Rawlins, M. D. Adverse reactions to N-acetylcysteine. Hum Toxicol. 1984;3(5):393-398. PubMed
  63. Gervais, S., Lussier-Labelle, F., and Beaudet, G. Anaphylactoid reaction to acetylcysteine. Clin Pharm 1984;3(6):586-587.
  64. Tattersall, A. B., Bridgman, K. M., and Huitson, A. Acetylcysteine (Fabrol) in chronic bronchitis--a study in general practice. J Int Med Res 1983;11(5):279-284. PubMed
  65. Casola, G. and vanSonnenberg, E. Skin damage from acetylcysteine leak during percutaneous abscess drainage. Radiology 1984;152(1):233. PubMed
  66. Aylward, M., Maddock, J., and Dewland, P. Clinical evaluation of acetylcysteine in the treatment of patients with chronic obstructive bronchitis: a balanced double-blind trial with placebo control. Eur.J Respir.Dis.Suppl 1980;111:81-89.
  67. Long-term oral acetylcysteine in chronic bronchitis. a double-blind controlled study. Eur.J Respir.Dis.Suppl 1980;111:93-108.
  68. Chan, T. Y. and Critchley, J. A. Adverse reactions to intravenous N-acetylcysteine in Chinese patients with paracetamol (acetaminophen) poisoning. Hum Exp.Toxicol. 1994;13(8):542-544. PubMed
  69. Hansen, N. C., Skriver, A., Brorsen-Riis, L., Balslov, S., Evald, T., Maltbaek, N., Gunnersen, G., Garsdal, P., Sander, P., Pedersen, J. Z., and . Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchiti
  70. Reid, M. B., Stokic, D. S., Koch, S. M., Khawli, F. A., and Leis, A. A. N-acetylcysteine inhibits muscle fatigue in humans. J Clin Invest 1994;94(6):2468-2474. PubMed
  71. Chirkov, Y. Y. and Horowitz, J. D. N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation. J Cardiovasc.Pharmacol 1996;28(3):375-380. PubMed
  72. Hershkovitz, E., Shorer, Z., Levitas, A., and Tal, A. Status epilepticus following intravenous N-acetylcysteine therapy. Isr.J Med Sci 1996;32(11):1102-1104.
  73. Stavem, K. [Anaphylactic reaction to N-acetylcysteine after poisoning with paracetamol]. Tidsskr.Nor Laegeforen. 5-30-1997;117(14):2038-2039.
  74. Walton, N. G., Mann, T. A., and Shaw, K. M. Anaphylactoid reaction to N-acetylcysteine. Lancet 12-15-1979;2(8155):1298. PubMed
  75. Perry, H. E. and Shannon, M. W. Efficacy of oral versus intravenous N-acetylcysteine in acetaminophen overdose: results of an open-label, clinical trial. J Pediatr 1998;132(1):149-152. PubMed
  76. Kory, R. C., Hirsch, S. R., and Giraldo, J. Nebulization of N-acetylcysteine combined with a bronchodilator in patients with chronic bronchitis. A controlled study. Chest 1968;54(6):504-509. PubMed
  77. Nahir, A. M., Scharf, J. M., and Szargel, R. Effects of oral N-acetylcysteine on both ocular and oral manifestations of Sjogren's Syndrome. Curr Ther Res 1989;46:187-192.
  78. Charley, G., Dean, B. S., and Krenzelok, E. P. Oral N-acetylcysteine-induced urticaria: a case report. Vet.Hum Toxicol. 1987;29:477.
  79. Jenkins DD, Wiest DB, Mulvihill DM, et al. Fetal and neonatal effects of N-acetylcysteine when used for neuroprotection in maternal chorioamnionitis. J Pediatr. 2016 Jan;168:67-76.e6. PubMed
  80. Costa DLC, Diniz JB, Requena G, et al. Randomized double-blind, placebo-controlled trial of N-acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry. 2017 Jul;78(7):e799-e773.
  81. Kranzer K, Elamin WF, Cox H, Seddon JA, Ford N, Drobniewski F. A systematic review and meta-analysis of the efficacy and safety of N-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB.
  82. Wang W, Zhang Y, Liu Y, Xu L, Shi D. Severe chest pain due to N-acetylcysteine-induced esophagitis. Case Rep Med. 2019;2019:8057259.
  83. Li F, Welling MC, Johnson JA, et al. N-acetylcysteine for pediatric obsessive-compulsive disorder: A small pilot study. J Child Adolesc Psychopharmacol. 2020;30(1):32-37. PubMed
  84. Monti DA, Zabrecky G, Leist TP, et al. N-acetyl cysteine administration is associated with increased cerebral glucose metabolism in patients with multiple sclerosis: An exploratory study. Front Neurol. 2020;11:88. PubMed
  85. Gray KM, Carpenter MJ, Baker NL, et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am J Psychiatry. 2012;169(8):805-12.
  86. Sarris J, Byrne G, Castle D, et al. N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 2022;117:110550 PubMed

See these in context on the N-acetyl Cysteine (nac) monograph →

Horny Goat Weed 11 references
  1. Cirigliano MD, Szapary PO. Horny goat weed for erectile dysfunction. Alt Med Alert 2001;4:19-22.
  2. Partin JF, Pushkin YR. Tachyarrhythmia and hypomania with horny goat weed. Psychosomatics 2004;45:536-7. PubMed
  3. De Naeyer A, Pocock V, Milligan S, De Keukeleire D. Estrogenic activity of a polyphenolic extract of the leaves of Epimedium brevicornum. Fitoterapia 2005;76:35-40. PubMed
  4. Zhang CZ, Wang SX, Zhang Y, et al. In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. J Ethnopharmacol 2005;98:295-300. PubMed
  5. Yap SP, Shen P, Li J, et al. Molecular and pharmacodynamic properties of estrogenic extracts from the traditional Chinese medicinal herb, Epimedium. J Ethnopharmacol 2007;113:218-24. PubMed
  6. Yan, F. F., Liu, Y., Liu, Y. F., and Zhao, Y. X. Herba Epimedii water extract elevates estrogen level and improves lipid metabolism in postmenopausal women. Phytother.Res. 2008;22(9):1224-1228. PubMed
  7. Ramanathan VS, Mitropoulos E, Shlopov B, et al. An Enzyte'ing' case of acute hepatitis. J Clin Gastroenterol 2011;45(9):834-5. PubMed
  8. Zhong Q, Shi Z, Zhang L, et al. The potential of Epimedium koreanum Nakai for herb-drug interaction. J Pharm Pharmacol 2017;69(10):1398-408. doi: 10.1111/jphp.12773.
  9. Irfan M, Kwon TH, Lee DH, et al. Antiplatelet and Antithrombotic Effects of Epimedium koreanum Nakai. Evid Based Complement Alternat Med. Apr 2021;2021:7071987. PubMed
  10. Tan K, Yang W, Pang L, Hou F. Differences in clinical characteristics among 726 patients with Chinese herbal medicine- or Western medicine-induced liver injury. Medicine (Baltimore) 2022;101(32):e29909. PubMed
  11. Li K, Yu XH, Maskey AR, et al. Cytochrome P450 3A4 suppression by epimedium and active compound kaempferol leads to synergistic anti-inflammatory effect with corticosteroid. Front Pharmacol 2023;13:1042756. PubMed

See these in context on the Horny Goat Weed monograph →

Black Pepper 29 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  3. Bano G, Amla V, Raina RK, et al. The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 1987;53:568-9. PubMed
  4. Bano G, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991;41;615-7. PubMed
  5. Cohle SD, Trestrail JD III, Graham MA, et al. Fatal pepper aspiration. Am J Dis Child 1988;142:633-6. PubMed
  6. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  7. Velpandian T, Jasuja R, Bhardwaj RK, et al. Piperine in food: interference in the pharmacokinetics of phenytoin. Eur J Drug Metab Pharmacokinet 2001;26:241-7. PubMed
  8. Pattanaik S, Hota D, Prabhakar S, et al. Pharmacokinetic interaction of a single dose of piperine with steady-state carbamazepine in epilepsy patients. Phytother Res 2009;23:1281-6.
  9. Munakata, M., Kobayashi, K., Niisato-Nezu, J., Tanaka, S., Kakisaka, Y., Ebihara, T., Ebihara, S., Haginoya, K., Tsuchiya, S., and Onuma, A. Olfactory stimulation using black pepper oil facilitates oral feeding in pediatric patients receiving long-term en
  10. Myers, B. M., Smith, J. L., and Graham, D. Y. Effect of red pepper and black pepper on the stomach. Am J Gastroenterol 1987;82(3):211-214.
  11. Raghavendra, R. H. and Naidu, K. A. Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis. Prostaglandins Leukot.Essent.Fatty Acids 2009;81(1):73-78. PubMed
  12. Subehan, Usia, T., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum. Planta Med 2006;72(6):527-532.
  13. Kasibhatta, R. and Naidu, M. U. Influence of piperine on the pharmacokinetics of nevirapine under fasting conditions: a randomised, crossover, placebo-controlled study. Drugs R.D. 2007;8(6):383-391. PubMed
  14. Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., and Tezuka, Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73. PubMed
  15. Mujumdar, A. M., Dhuley, J. N., Deshmukh, V. K., Raman, P. H., Thorat, S. L., and Naik, S. R. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp.Biol. 1990;28(5):486-487.
  16. Panda, S. and Kar, A. Piperine lowers the serum concentrations of thyroid hormones, glucose and hepatic 5'D activity in adult male mice. Horm.Metab Res. 2003;35(9):523-526. PubMed
  17. Lawless, H. and Stevens, D. A. Effects of oral chemical irritation on taste. Physiol Behav. 1984;32(6):995-998. PubMed
  18. Hiwale, A. R., Dhuley, J. N., and Naik, S. R. Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats. Indian J Exp.Biol. 2002;40(3):277-281.
  19. Han, Y., Chin Tan, T. M., and Lim, L. Y. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol.Appl.Pharmacol. 8-1-2008;230(3):283-289. PubMed
  20. Sharma, P., Varma, M. V., Chawla, H. P., and Panchagnula, R. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Farmaco 2005;60(11-12):874-883. PubMed
  21. Aher, S., Biradar, S., Gopu, C. L., and Paradkar, A. Novel pepper extract for enhanced P-glycoprotein inhibition. J Pharm.Pharmacol. 2009;61(9):1179-1186. PubMed
  22. Zutshi, R. K., Singh, R., Zutshi, U., Johri, R. K., and Atal, C. K. Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis. J Assoc.Physicians India 1985;33(3):223-224.
  23. Marotta, R. B. and Floch, M. H. Diet and nutrition in ulcer disease. Med Clin North Am 1991;75(4):967-979. PubMed
  24. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
  25. Gimenez L, Zacharisen M. Severe pepper allergy in a young child. WMJ. 2011 Jun;110(3):138-9.
  26. Ren T, Yang M, Xiao M, Zhu J, Xie W, Zuo Z. Time-dependent inhibition of carbamazepine metabolism by piperine in anti-epileptic treatment. Life Sci. 2019;218:314-323. PubMed
  27. Thomas AB, Choudhary DC, Raje A, Nagrik SS. Pharmacokinetics and pharmacodynamic herb-drug interaction of piperine with atorvastatin in rats. J Chromatogr Sci 2021;59(4):371-80. PubMed
  28. 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
  29. Lin F, Hu Y, Zhang Y, Zhao L, Zhong D, Liu J. Predicting Food-Drug Interactions between Piperine and CYP3A4 Substrate Drugs Using PBPK Modeling. Int J Mol Sci 2024;25(20):10955. PubMed

See these in context on the Black Pepper monograph →

Bergamot 17 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  3. Naganuma M, Hirose S, Nakayama Y, et al. A study of the phototoxicity of lemon oil. Arch Dermatol Res 1985;278:31-6. . PubMed
  4. Kaddu, S., Kerl, H., and Wolf, P. Accidental bullous phototoxic reactions to bergamot aromatherapy oil. J.Am.Acad.Dermatol. 2001;45(3):458-461. PubMed
  5. Finsterer, J. Earl Grey tea intoxication. Lancet 4-27-2002;359(9316):1484. PubMed
  6. Gruson, L. M. and Chang, M. W. Berloque dermatitis mimicking child abuse. Arch.Pediatr.Adolesc.Med. 2002;156(11):1091-1093. PubMed
  7. Weisenseel, P. and Woitalla, S. [Toxic mustard plaster dematitis and phototoxic dematitis after application of bergamot oil]. MMW.Fortschr.Med. 12-15-2005;147(51-52):53, 55.
  8. Placzek, M., Fromel, W., Eberlein, B., Gilbertz, K. P., and Przybilla, B. Evaluation of phototoxic properties of fragrances. Acta Derm.Venereol. 2007;87(4):312-316. PubMed
  9. Mollace, V., Sacco, I., Janda, E., Malara, C., Ventrice, D., Colica, C., Visalli, V., Muscoli, S., Ragusa, S., Muscoli, C., Rotiroti, D., and Romeo, F. Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies. F PubMed
  10. Morliere, P., Huppe, G., Averbeck, D., Young, A. R., Santus, R., and Dubertret, L. In vitro photostability and photosensitizing properties of bergamot oil. Effects of a cinnamate sunscreen. J.Photochem.Photobiol.B 1990;7(2-4):199-208. PubMed
  11. Young, A. R., Walker, S. L., Kinley, J. S., Plastow, S. R., Averbeck, D., Morliere, P., and Dubertret, L. Phototumorigenesis studies of 5-methoxypsoralen in bergamot oil: evaluation and modification of risk of human use in an albino mouse skin model. J.P PubMed
  12. Girard, J., Unkovic, J., Delahayes, J., and Lafille, C. [Phototoxicity of Bergamot oil. Comparison between humans and guinea pigs]. Dermatologica 1979;158(4):229-243.
  13. Zaynoun, S. T., Johnson, B. E., and Frain-Bell, W. A study of oil of bergamot and its importance as a phototoxic agent. II. Factors which affect the phototoxic reaction induced by bergamot oil and psoralen derivatives. Contact Dermatitis 1977;3(5):225-23 PubMed
  14. Zacher, K. D. and Ippen, H. [Contact dermatitis caused by bergamot oil]. Derm.Beruf.Umwelt. 1984;32(3):95-97.
  15. Yasui, Y. and Hirone, T. Action spectrum for bergamot-oil phototoxicity measured by sunburn cell counting. J.Dermatol. 1994;21(5):319-322. PubMed
  16. Zaynoun, S. T., Johnson, B. E., and Frain-Bell, W. A study of oil of bergamot and its importance as a phototoxic agent. I. Characterization and quantification of the photoactive component. Br.J.Dermatol. 1977;96(5):475-482. PubMed
  17. Bruno A, Pandolfo G, Crucitti M, Cedro C, Zoccali RA, Muscatello MRA. Bergamot Polyphenolic Fraction Supplementation Improves Cognitive Functioning in Schizophrenia: Data From an 8-Week, Open-Label Pilot Study. J Clin Psychopharmacol 2017;37(4):468-71. PubMed

See these in context on the Bergamot monograph →

Ashwagandha 32 references
  1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  2. Upton R, ed. Ashwagandha Root (Withania somnifera): Analytical, quality control, and therapuetic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 2000:1-25.
  3. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett 2000;148:9-17. PubMed
  4. Davis L, Kuttan G. Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol 1998;62:209-14. PubMed
  5. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev 2000;5:334-46. DOI
  6. Andallu B, Radhika B. Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root. Indian J Exp Biol 2000;38:607-9.
  7. Kulkarni RR, Patki PS, Jog VP, et al. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 1991;33:91-5. PubMed
  8. Ahumada F, Aspee F, Wikman G, Hancke J. Withania somnifera exract. Its effects on arterial blood pressure in anaesthetized dogs. Phytother Res 1991;5:111-14.
  9. Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol 1999;67:233-39. PubMed
  10. Panda S, Kar A. Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice. J Pharm Pharmacol 1998;50:1065-68. PubMed
  11. Sehgal, V. N., Verma, P., and Bhattacharya, S. N. Fixed-drug eruption caused by ashwagandha (Withania somnifera): a widely used Ayurvedic drug. Skinmed. 2012;10(1):48-49.
  12. Agnihotri AP, Sontakke SD, Thawani VR, Saoji A, Goswami VS. Effects of Withania somnifera in patients of schizophrenia: a randomized, double blind, placebo controlled pilot trial study. Indian J Pharmacol. 2013;45(4):417-8. PubMed
  13. Biswal BM, Sulaiman SA, Ismail HC, Zakaria H, Musa KI. Effect of Withania somnifera (Ashwagandha) on the development of chemotherapy-induced fatigue and quality of life in breast cancer patients. Integr Cancer Ther. 2013;12(4):312-22.
  14. Sharma AK, Basu I, Singh S. Efficacy and safety of Ashwagandha root extract in subclinical hypothyroid patients: a double-blind, randomized placebo-controlled trial. J Altern Complement Med. 2018 Mar;24(3):243-248. PubMed
  15. Durg S, Bavage S, Shivaram SB. Withania somnifera (Indian ginseng) in diabetes mellitus: A systematic review and meta-analysis of scientific evidence from experimental research to clinical application. Phytother Res. 2020;34(5):1041-1059.
  16. Björnsson HK, Björnsson ES, Avula B, et al. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver Int. 2020;40(4):825-829. PubMed
  17. Tharakan A, Shukla H, Benny IR, Tharakan M, George L, Koshy S. Immunomodulatory Effect of Withania somnifera (Ashwagandha) Extract-A Randomized, Double-Blind, Placebo Controlled Trial with an Open Label Extension on Healthy Participants. J Clin Med 2021;1 PubMed
  18. Ireland PJ, Hardy T, Burt AD, Donnelly MC. Drug-induced hepatocellular injury due to herbal supplement ashwagandha. J R Coll Physicians Edinb. 2021;51(4):363-365. PubMed
  19. Kamal HI, Patel K, Brdak A, Heffernan J, Ahmad N. Ashwagandha as a unique cause of thyrotoxicosis presenting with supraventricular tachycardia. Cureus. 2022 Mar 25;14(3):e23494. PubMed
  20. Suryawanshi G, Abdallah M, Thomson M, Desai N, Chauhan A, Lim N. Ashwagandha-Associated Acute Liver Failure Requiring Liver Transplantation. Am J Ther 2023;30(1):e80-e83. PubMed
  21. Pusec CM, Wolsky R, Llerena C, Sura P. A Case of Supplement-Induced Hepatitis. Cureus 2022;14(10):e30433. PubMed
  22. Ajgaonkar A, Jain M, Debnath K. Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract for Improvement of Sexual Health in Healthy Women: A Prospective, Randomized, Placebo-Controlled Study. Cureus 2022;14(10):e30787. PubMed
  23. 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
  24. Lubarska M, Halasinski P, Hryhorowicz S, et al. Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury. Int J Environ Res Public Health 2023;20(5):3921. PubMed
  25. Tóth M, Benedek AE, Longerich T, Seitz HK. Ashwagandha-induced acute liver injury: A case report. Clin Case Rep 2023;11(3):e7078.
  26. Bokan G, Glamocanin T, Mavija Z, et al. Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. Pharmaceuticals (Basel) 2023;16(8):1129. PubMed
  27. Patel PA, Sanborn E, Then R, Williams DM. Recurrent Reversible Cerebral Vasoconstriction Syndrome: A Report of Two Cases. Cureus 2023;15(8):e42992. PubMed
  28. Majeed M, Nagabhushanam K, Murali A, Vishwanathan DT, Mamidala RV, Mundkur L. A Standardized Withania somniferra (Linn.) Root Extract with Piperine Alleviates the Symptoms of Anxiety and Depression by Increasing Serotonin Levels: A Double-Blind, Randomize
  29. Philips CA, Valsan A, Theruvath AH, et al. Ashwagandha-induced liver injury-A case series from India and literature review. Hepatol Commun 2023;7(10):e0270. PubMed
  30. Hayashi M, Hamada H, Azuma SI, Hayashi K. Painless Thyroiditis by Withania somnifera (Ashwagandha). Cureus 2024;16(3):e55352. PubMed
  31. Vazirani S, Kothari A, Fujimoto J, Gomez M. Supplements Are Not a Synonym for Safe: Suspected Liver Injury From Ashwagandha. Fed Pract 2023;40(9):315-319. PubMed
  32. Patel M, Newell R, Hillier M, Ramalingam R. Herbal remedies as a potential cause of hypoadrenalism. Br J Hosp Med (Lond) 2024;85(6):1-4. PubMed

See these in context on the Ashwagandha 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 →

Arimistane 1 reference
  1. Joseph JF, Parr MK. Synthetic androgens as designer supplements. Curr Neuropharmacol. 2015;13(1):89-100. PubMed

See these in context on the Arimistane 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
Supplement interaction checker › Check any supplement or product against your medications Drug–drug interactions › Check two or more of your medications against each other Browse medications A–Z › Every drug we've checked against herbs & supplements NDC & pricing lookup › Find a drug’s NDCs, packaging and costs Ask a pharmacist › Free, personal answer from our licensed team