Major interaction on record — check this product against your medications before combining. Based on 7 of 9 ingredients. Check your meds →
Dietary supplement

Herbal Female Complex Ingredients & Drug Interactions

by Solgar

Herbal Female Complex label
See full label image
Capsule Category: Botanical With Nutrients
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 9, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Herbal Female Complex 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

Herbal Female Complex is a dietary supplement by Solgar with 9 active ingredients. Its ingredients are commonly taken for iron-deficiency anemia, low iron stores during pregnancy, fatigue from iron deficiency.Based on those ingredients, 1,632 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are standardized Milk Thistle extract, Black Cohosh extract, Soy Isoflavone 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 Herbal Female Complex by Solgar

Ask about any prescription or over-the-counter medication and we check it for interactions with Herbal Female Complex by Solgar — 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 Herbal Female Complex by Solgar

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 9 of its 9 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Herbal Female Complex contains nine ingredients, five of which are active: iron, raw astragalus powder, raw dong quai powder, standardized chaste extract, standardized dong quai extract, soy isoflavone extract, standardized milk thistle extract, black cohosh extract, and motherwort extract. Iron is included to support healthy blood production; the botanical ingredients (astragalus, dong quai, chaste, milk thistle, black cohosh, and motherwort) are traditional herbs used in women's health formulations.

Soy isoflavones contribute plant-derived compounds. The product also contains inactive ingredients—vegetable cellulose, vegetable magnesium stearate, microcrystalline cellulose, and a proprietary PhytO2X blend—which serve as capsule material and binders.

Does it work?

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

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

Why this rating?
  • The label markets this product for: herbal support for women's health.
  • We looked for evidence on: Amenorrhea, Anxiety, Dysmenorrhea, Fatigue, menopause symptoms, premenstrual syndrome — and 1 related terms.
  • The closest evidence on file: Soy is rated "Possibly Ineffective" for Breast cancer-related hot flashes (Natural Medicines).
  • Also on file: Motherwort is rated "Insufficient Reliable Evidence To Rate" for Amenorrhea, Anxiety, Dysmenorrhea.
  • Also on file: Black Cohosh is rated "Insufficient Reliable Evidence To Rate" for Anxiety, Breast cancer-related hot flashes, Premenstrual syndrome (PMS).

The evidence for this product's effectiveness is mixed and ingredient-dependent. Iron is effective for iron deficiency anemia, anemia of chronic disease, and pregnancy-related iron deficiency, and possibly effective for heart failure.

For the botanical ingredients, the data we hold shows insufficient reliable evidence for most uses—astragalus, dong quai, and motherwort all lack established proof of benefit for the conditions commonly listed. Soy isoflavones are possibly effective for diabetes, elevated cholesterol, osteoporosis, high blood pressure, and diarrhea.

Milk thistle is possibly effective for diabetes. Black cohosh is possibly effective for menopausal symptoms.

Because this is a combination product with multiple ingredients of varying efficacy, its overall usefulness depends on your specific health goal—talk with your pharmacist or doctor about whether this formula matches what you're looking for.

The evidence, ingredient by ingredient Iron Astragalus Dong Quai Soy Milk Thistle Black Cohosh Motherwort

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 7 of the 7 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 7 of 7.
  • General safety write-ups exist for 7 of 7.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Iron is generally well tolerated at recommended doses; common side effects are abdominal pain, constipation, diarrhea, nausea, and vomiting. Excess iron can be toxic, so supplements should be used only when there's a real need.

Astragalus is generally well tolerated short-term in healthy adults, though human safety data are limited. Dong quai (in both forms) is generally well tolerated but may increase bleeding risk and cause skin sensitivity to sunlight.

Soy isoflavones are well tolerated; common effects are bloating, constipation, diarrhea, and nausea. Milk thistle is well tolerated, though gastrointestinal upset and rare allergic reactions have been reported.

Black cohosh is generally well tolerated short-term; common effects include dizziness, headache, and gastrointestinal upset, though rare liver concerns exist. Motherwort may cause diarrhea and stomach irritation, and topical exposure can cause contact dermatitis or photosensitivity.

Side effects, ingredient by ingredient Iron Astragalus Dong Quai Soy Milk Thistle Black Cohosh Motherwort

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?
  • 7 of the 7 matched ingredients can interact with medications — Motherwort, Milk Thistle, Black Cohosh, Iron, Dong Quai, 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; lithium; Parkinson's medications.
  • For scale: 1,633 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, check with your pharmacist if you take: blood thinners like warfarin (warfarin interaction is Major with dong quai); MAOIs or other serotonergic antidepressants; thyroid medication (levothyroxine); diabetes medications; blood pressure medications; tetracycline or quinolone antibiotics; bisphosphonates; lithium; immunosuppressants; or any drug metabolized by your liver. Iron, dong quai, and soy all have multiple interactions that spacing doses may help—your pharmacist can advise on timing.

Check your own medication Run your meds through the checker above

The bottom line

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

This product combines iron with multiple botanicals and is best suited for people specifically looking for traditional women's health support and who do not take blood thinners, thyroid medication, diabetes drugs, or certain antibiotics. If you take any prescription medications—especially blood thinners like warfarin, antidepressants (especially MAOIs or serotonergic drugs), thyroid medication, or diabetes drugs—check with your pharmacist before starting.

The iron and herbs work best when doses of interacting medications are spaced apart.

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

Assessment coverage: 8 of 9 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Oct 1, 2012.

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 Herbal Female Complex, straight from the product label.

Brand Solgar
Net contents 50 Vegetable Capsule(s)
Market status On market
Date entered into DSLD Oct 1, 2012
DSLD ID 13295
Product type Botanical With Nutrients
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegetarian, Adult Female (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 Herbal Female Complex by Solgar, 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:
1 Vegetarian Capsule(s)
Maximum serving Sizes:
1 Vegetarian Capsule(s)
IngredientAmount% DV
Total Carbohydrates1 g1%
Iron1 mg6%
raw Astragalus powder75 mg--
raw Dong Quai powder50 mg--
standardized Chaste extract75 mg--
standardized Dong Quai extract75 mg--
Soy Isoflavone Extract100 mg--
standardized Milk Thistle extract50 mg--
Black Cohosh extract100 mg--
Motherwort extract75 mg--

Other ingredients: Vegetable Cellulose, Vegetable Magnesium Stearate, Microcrystalline Cellulose, PhytO2X Blend

Tap any ingredient to jump to its full detail below.

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

Since 1947

STANDARDIZED - FULL POTENCY

FDA Disclaimer Statement

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

FDA Statement of Identity

HERBAL DIETARY SUPPLEMENT

Formulation

SUITABLE FOR VEGETARIANS

Suggested/Recommended/Usage/Directions

SUGGESTED USE: As an herbal dietary supplement for adults, take one (1) vegetable capsule up to three (3) times daily, preferably at mealtime, or as directed by a healthcare practitioner.

Precautions

WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

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

Keep out of reach of children.

Brand IP Statement(s)

PhytO2X(R) System

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

See for yourself

Herbal Female Complex by Solgar label

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

Herbal Female Complex 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 Herbal Female Complex by Solgar

These are the 9 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Vegetarian Capsule(s) Dosage formCapsule 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.

Iron

Interacts with
80 drugs
1 mg per serving

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventin...

Iron monograph & interactions

Raw Astragalus powder

Interacts with
208 drugs
75 mg per serving

Astragalus is a root used for centuries in traditional Chinese medicine, mainly to support the immune system and help the body cope with stress. While...

Raw Astragalus powder monograph & interactions

Raw Dong Quai powder

Interacts with
163 drugs
50 mg per serving

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

Raw Dong Quai powder monograph & interactions

Standardized Chaste extract

75 mg per serving Form: Agnuside

Standardized Dong Quai extract

Interacts with
163 drugs
75 mg per serving Form: Ligustilide

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

Standardized Dong Quai extract monograph & interactions

Soy Isoflavone Extract

Interacts with
611 drugs
100 mg per serving

Soy is a nutritious bean that is a staple food and a popular source of plant protein and isoflavones. Eating soy foods as part of a balanced diet is g...

Soy Isoflavone Extract monograph & interactions

Standardized Milk Thistle extract

Interacts with
954 drugs
50 mg per serving Form: Silymarin

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....

Standardized Milk Thistle extract monograph & interactions

Black Cohosh extract

Interacts with
652 drugs
100 mg per serving

Black cohosh is a North American plant most often used to ease menopause symptoms like hot flashes, but the research is mixed and far from settled. It...

Black Cohosh extract monograph & interactions

Motherwort extract

Interacts with
248 drugs
75 mg per serving

Motherwort is a traditional herb in the mint family long used for anxiety, heart palpitations, and women's reproductive complaints, but solid human ev...

Motherwort extract monograph & interactions

Other (inactive) ingredients: Vegetable Cellulose, Vegetable Magnesium Stearate, Microcrystalline Cellulose, PhytO2X Blend. These complete the product’s ingredient list but are not active constituents.

Interaction report

Herbal Female Complex by Solgar Drug Interactions

Want to check YOUR meds against Herbal Female Complex?

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
1,632Drugs
11 Major 1,235 Moderate 386 Minor

Ingredients driving the most interactions

standardized Milk Thistle extract 954
Black Cohosh extract 652
Soy Isoflavone Extract 611
Motherwort extract 248
raw Astragalus powder 208

Individual Drug Interactions

The ingredients in Herbal Female Complex interact with 1,632 drugs. Click any drug to see the details.

7 of the 9 ingredients in Herbal Female Complex interact with drugs. Each result below shows which ingredient is responsible. standardized Milk Thistle extract Black Cohosh extract Soy Isoflavone Extract Motherwort extract raw Astragalus powder raw Dong Quai powder Iron

Each ingredient & the kinds of drugs it affects

For each ingredient in Herbal Female Complex 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.

standardized Milk Thistle extract17 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
standardized Milk Thistle extract full monograph & interactions

Black Cohosh extract7 drug types · 652 drugs

Atorvastatin (Lipitor)

Taking black cohosh with atorvastatin might increase the risk for elevated liver function tests.
In one case report, a patient taking atorvastatin (Lipitor) developed significantly elevated liver function enzymes after starting black cohosh 100 mg four times daily. Liver enzymes returned to normal when black cohosh was discontinued. It is unclear whether the elevated liver enzymes were due to black cohosh itself or an interaction between atorvastatin and black cohosh.

Likelihood Possible Evidence D
Cisplatin (Platinol-Aq)

Theoretically, black cohosh may reduce the clinical effects of cisplatin.
Animal research suggests that black cohosh might decrease the cytotoxic effect of cisplatin on breast cancer cells.

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

Some research suggests that black cohosh might inhibit CYP2D6, but there is conflicting evidence.
Some clinical research suggests that black cohosh might modestly inhibit CYP2D6 and increase levels of drugs metabolized by this enzyme. However, contradictory clinical research shows a specific black cohosh product (Remifemin, Enzymatic Therapy) 40 mg twice daily does not significantly inhibit metabolism of a CYP2D6 substrate in healthy study volunteers. Until more is known, use black cohosh cautiously in patients taking drugs metabolized by CYP2D6.

Likelihood Possible Evidence B
Estrogens

Theoretically, black cohosh may alter the effects of estrogen therapy.
Some research suggests that black cohosh has estrogenic effects. This may enhance or inhibit the effects of estrogen therapy.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.
There is concern that black cohosh might be linked to cases of liver failure and autoimmune hepatitis.

Likelihood Possible Evidence D
Serotonergic Drugs

Combining serotonergic drugs with black cohosh might cause additive serotonergic effects.
Black cohosh might increase the risk of serotonin syndrome when combined with other serotonergic drugs. Black cohosh acts as an agonist at several serotonin receptor subtypes and might interact with other serotonergic medications. In one case, a 55-year-old female who had been on stable treatment with sertraline 50 mg and duloxetine 60 mg daily developed serotonin syndrome after taking black cohosh extract 40 mg daily for 3 days.

Likelihood Possible Evidence D
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Black cohosh may inhibit one form of OATP, OATP2B1, which could reduce the bioavailability and clinical effects of OATP2B1 substrates.
In vitro research shows that black cohosh modestly inhibits OATP2B1. 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
Black Cohosh extract full monograph & interactions

Soy Isoflavone Extract12 drug types · 611 drugs

Monoamine Oxidase Inhibitors (Maois)

Taking soy products containing high amounts of tyramine along with MAOIs can increase the risk of hypertensive crisis.
Fermented soy products such as tofu and soy sauce contain tyramine, a naturally occurring chemical that affects blood pressure regulation. The metabolism of tyramine is decreased by MAOIs. Consuming more than 6 mg of tyramine while taking an MAOI can increase the risk of hypertensive crisis. The amount of tyramine in fermented soy products is usually less than 0.6 mg per serving; however, there can be significant variation depending on the specific product used, storage conditions, and length of storage. Storing one brand of tofu for a week can increase tyramine content from 0.23 mg to 4.8 mg per serving. Advise patients taking MAOIs to avoid fermented soy products that contain high amounts of tyramine.

Likelihood Likely Evidence C
Antidiabetes Drugs

Soy can lower blood glucose and have additive effects with antidiabetes drugs.
Clinical research shows that whole soy diets and soy-based meals reduce fasting glucose levels in diabetic and non-diabetic individuals. Also, individuals following a soy-based meal replacement plan seem to require lower doses of sulfonylureas and metformin to manage blood glucose levels when compared with individuals following a diet plan recommended by the American Diabetes Association.

Likelihood Possible Evidence A
Antihypertensive Drugs

Theoretically soy protein may have additive effects with antihypertensive drugs and increase the risk of hypotension.
Although some contradictory research exists, most clinical evidence suggests that consuming soy protein modestly reduces systolic and diastolic blood pressure in individuals with prehypertension or hypertension.

Likelihood Possible Evidence A
Caffeine

Theoretically, soy might reduce the clearance of caffeine.
Soy contains genistein. Taking genistein 1 gram daily for 14 days seems to inhibit caffeine clearance and metabolism in healthy females. This effect has been attributed to inhibition of the cytochrome P450 1A2 (CYP1A2) enzyme, which is involved in caffeine metabolism. It is unclear if this effect occurs with the lower amounts of genistein found in soy.

Likelihood Possible Evidence D
Diuretic Drugs

Theoretically, soy might have additive effects when used with diuretic drugs.
Animal research suggests that genistein, a soy isoflavone, increases diuresis within 6 hours of subcutaneous administration in rats. The effects seem to be similar to those of furosemide. This effect has not been reported in humans.

Likelihood Possible Evidence D
Estrogens

Theoretically, soy might competitively inhibit the effects of estrogen replacement therapy.
Soy contains phytoestrogens and has been shown to have estrogenic activity in some patients. Although this has not been demonstrated in humans, theoretically, concomitant use of soy with estrogen replacement therapy might reduce the effects of the estrogen replacement therapy.

Likelihood Possible Evidence D
Levothyroxine (Synthroid, Others)

Soy products might reduce the absorption of levothyroxine in some patients.
Preliminary clinical research and a case report suggest that soy-based formulas inhibit the absorption of levothyroxine in infants with congenital hypothyroidism. A levothyroxine dosage increase may be needed for infants with congenital hypothyroidism while using soy-based formulas, and the dose may need to be reduced when soy-based formulas are no longer administered. However, in postmenopausal adults, clinical research shows that taking a single dose of soy extract containing isoflavones 60 mg along with levothyroxine does not affect the oral bioavailability of levothyroxine.

Likelihood Possible Evidence B
Progesterone

Theoretically, combining soy isoflavones with transdermal progesterone may worsen bone density.
Clinical research suggests that significant bone loss may occur in females with osteoporosis who receive a combination of transdermal progesterone with soy milk containing isoflavones when compared with placebo, soy milk alone, or progesterone alone.

Likelihood Possible Evidence A
Tamoxifen (Nolvadex)

Theoretically, estrogenic soy isoflavones might alter the effects of tamoxifen.
Laboratory research suggests that genistein and daidzen, isoflavones from soy, can antagonize the antitumor effects of tamoxifen under some circumstances; however, soy isoflavones might have different effects when used at different doses. A relatively low in vitro concentration of soy isoflavones such as 1 microM/L seems to interfere with tamoxifen, whereas high in vitro concentrations such as those >10 microM/L might actually enhance tamoxifen effects. People on a high-soy diet have soy isoflavones levels ranging from 0.1-6 microM/L. Until more is known, advise patients taking tamoxifen to avoid therapeutic use of soy products.

Likelihood Possible Evidence B
Warfarin (Coumadin)

Theoretically, soy might interfere with the effects of warfarin.
Soy milk has been reported to decrease the international normalized ratio (INR) in a patient taking warfarin. The mechanism of this interaction is not known. However, animal and in vitro research suggests that soy may also inhibit platelet aggregation. Dosing adjustments for warfarin may be necessary.

Likelihood Possible Evidence D
Antibiotic Drugs

Theoretically, antibiotics may decrease the activity of soy isoflavones.
Intestinal bacteria are responsible in part for converting soy isoflavones into their active forms. Antibiotics may decrease the amount of intestinal bacteria and decrease its ability to convert isoflavones.

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

Soy might modestly induce CYP2C9 enzymes. However, this effect does not seem to be clinically significant.
In vitro research suggests that an unhydrolyzed soy extract might induce CYP2C9. However, the significance of this interaction is likely minimal. In healthy females taking a specific extract of soy (Genistein Soy Complex, Source Naturals), blood levels of losartan, a CYP2C9 substrate, were not significantly affected.

Likelihood Unlikely Evidence D
Soy Isoflavone Extract full monograph & interactions

Motherwort extract1 drug type · 248 drugs

Cns Depressants

Theoretically, taking motherwort concomitantly with other CNS depressants may increase the risk of sedation.
Motherwort has been reported to cause CNS depression and sedation.

Likelihood Possible Evidence D
Motherwort extract full monograph & interactions

raw Astragalus powder4 drug types · 208 drugs

Antidiabetes Drugs

Theoretically, taking astragalus with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research in humans shows that astragalus might have hypoglycemic effects. Theoretically, taking astragalus, especially in combination with other hypoglycemic agents, might increase the risk of hypoglycemia.

Likelihood Probable Evidence A
Cyclophosphamide

Theoretically, astragalus might interfere with cyclophosphamide therapy.
Evidence regarding the effect of astragalus on immunosuppression caused by cyclophosphamide is conflicting. Some animal research suggests that astragalus reverses cyclophosphamide-induced immunosuppression. However, other animal research shows no effect.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, astragalus might interfere with immunosuppressive therapy.
Astragalus seems to stimulate immune function. Theoretically, taking astragalus might decrease the effects of immunosuppressive therapy.

Likelihood Possible Evidence D
Lithium

Theoretically, astragalus might increase levels and adverse effects of lithium.
Animal research suggests that astragalus has diuretic properties. Theoretically, due to this diuretic effect, astragalus might reduce excretion and increase levels of lithium.

Likelihood Probable Evidence D
raw Astragalus powder full monograph & interactions

raw Dong Quai powder3 drug types · 163 drugs

Warfarin (Coumadin)

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Possible Evidence D
raw Dong Quai powder full monograph & interactions

Iron13 drug types · 80 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Iron might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption when taken in a fasting state.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide and iron can be taken together if taken with food. However, if taken on an empty stomach, bictegravir/emtricitabine/tenofovir alafenamide should not be taken with, or 2 hours after, iron containing products.

Likelihood Probable Evidence D
Bisphosphonates

Iron reduces the absorption of bisphosphonates.
Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron. Divalent cations, including iron, can decrease absorption of bisphosphonates by forming insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence D
Denosumab (Prolia, Others)

Administration of intravenous iron within one month of denosumab administration might increase the risk of severe hypophosphatemia and hypocalcemia.
A case of severe hypocalcemia (albumin corrected calcium 6.88 mg/dL, ionized calcium 3.68 mg/dL) and hypophosphatemia (<0.5 mg/dL) with respiratory acidosis, QT interval prolongation, and nonsustained ventricular tachycardia was reported in a 76-year-old male who had received an iron polymaltose infusion within 2 weeks of a subcutaneous injection of denosumab. Serum parathyroid hormone was also elevated (348 pg/mL). Subsequent iron infusions with iron polymaltose and ferric carboxymaltose were followed by transient hypophosphatemia, but without hypocalcemia. Additionally, a literature review describes 6 additional cases of hypophosphatemia and hypocalcemia in patients 52-92 years of age who had been administered intravenous iron as either ferric carboxymaltose or iron polymaltose and subcutaneous denosumab within 1-4 weeks of each other.

Likelihood Possible Evidence D
Dolutegravir (Tivicay)

Iron might decrease dolutegravir levels by reducing its absorption.
Advise patients to take dolutegravir at least 2 hours before or 6 hours after taking iron. Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation. When taken under fasting conditions, a single dose of ferrous fumarate 324 mg orally along with dolutegravir 50 mg reduces overall exposure to dolutegravir by 54%.

Likelihood Probable Evidence B
Integrase Inhibitors

Theoretically, taking iron along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Iron is a divalent cation. There is concern that iron may decrease the absorption of integrase inhibitors from the gastrointestinal tract through chelation. One pharmacokinetic study shows that iron can decrease blood levels of the specific integrase inhibitor dolutegravir through chelation. Also, other pharmacokinetic research shows that other divalent cations such as calcium can decrease the absorption and levels of some integrase inhibitors through chelation.

Likelihood Possible Evidence D
Levodopa

Iron might decrease levodopa levels by reducing its absorption.
Advise patients to separate doses of levodopa and iron as much as possible. There is some evidence in healthy people that iron forms chelates with levodopa, reducing the amount of levodopa absorbed by around 50%. The clinical significance of this hasn't been determined.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Iron might decrease levothyroxine levels by reducing its absorption.
Advise patients to separate levothyroxine and iron doses by at least 2 hours. Iron can decrease the absorption and efficacy of levothyroxine by forming insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence B
Methyldopa (Aldomet)

Iron might decrease methyldopa levels by reducing its absorption.
Advise patients to separate methyldopa and iron doses by at least 2 hours. Iron can decrease the absorption of methyldopa from the gastrointestinal tract through chelation, resulting in increases in blood pressure.

Likelihood Probable Evidence B
Mycophenolate Mofetil (Cellcept)

Theoretically, iron might decrease mycophenolate mofetil levels by reducing its absorption.
Advise patients to take iron 4-6 hours before, or 2 hours after, mycophenolate mofetil. It has been suggested that a decrease of absorption is possible, probably by forming nonabsorbable chelates. However, mycophenolate pharmacokinetics are not affected by iron supplementation in available clinical research.

Likelihood Unlikely Evidence D
Penicillamine (Cuprimine, Depen)

Iron might decrease penicillamine levels by reducing its absorption.
Advise patients to separate penicillamine and iron doses by at least 2 hours. Oral iron supplements can reduce absorption of penicillamine by 30% to 70%, probably due to chelate formation. In people with Wilson's disease, this interaction has led to reduced efficacy of penicillamine.

Likelihood Probable Evidence D
Quinolone Antibiotics

Iron might decrease levels of quinolone antibiotics by reducing their absorption.
Advise patients to separate quinolone antibiotics and iron doses by at least 2 hours. Iron decreases the absorption of quinolones due to formation of insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence D
Tetracycline Antibiotics

Iron might decrease levels of tetracycline antibiotics by reducing their absorption.
Advise patients to take iron at least 2 hours before or 4 hours after tetracycline antibiotics. Concomitant use can decrease absorption of tetracycline antibiotics from the gastrointestinal tract by 50% to 90%.

Likelihood Probable Evidence D
Chloramphenicol

Theoretically, taking chloramphenicol with iron might reduce the response to iron therapy in iron deficiency anemia.
Chloramphenicol interferes with erythrocyte maturation. However, since chloramphenicol isn't usually taken for prolonged periods, this isn't likely to be clinically significant.

Likelihood Unlikely Evidence D
Iron full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Herbal Female Complex, from the product label.

Solgar

See all Solgar products
Name
Solgar
Pharmacist Counseling Corner

Herbal Female Complex by Solgar: Common Questions

Does Herbal Female Complex by Solgar interact with any medications?
Yes. Based on its ingredients, Herbal Female Complex has a known interaction with 1,632 medications, including 11 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Herbal Female Complex contains 9 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.
Is this safe to take during pregnancy?
The safety picture is mixed. Iron is considered likely safe in pregnancy when guided by your prenatal care provider. However, astragalus, dong quai, black cohosh, and motherwort should be avoided—the data advises against their use because there isn't enough safety information or because they may stimulate the uterus and affect bleeding. Talk with your obstetrician or midwife before using this product if you're pregnant.
Is it safe while breastfeeding?
Again, it depends on the ingredient. Iron is generally considered acceptable while breastfeeding at appropriate doses. Soy foods are commonly eaten while breastfeeding, but concentrated isoflavone supplements haven't been well studied. Astragalus, dong quai, black cohosh, and motherwort should be avoided while breastfeeding due to insufficient safety data. Check with your healthcare provider before using.
What is iron in here for?
Iron supports healthy blood production and is effective for iron deficiency anemia, anemia of chronic disease, and pregnancy-related iron deficiency. It's also possibly effective for heart failure. If you don't have a documented iron deficiency, excess iron can build up and become toxic, so supplements should be used only when there's a real need.
Can this help with menopausal symptoms?
Black cohosh in this product is possibly effective for menopausal symptoms based on clinical research. The other botanicals—astragalus, dong quai, chaste, milk thistle, and motherwort—lack sufficient reliable evidence for us to rate them for this use, though they're traditional in women's health formulas. Your results may vary.
What are the most common side effects?
From iron: abdominal pain, constipation, diarrhea, nausea, and vomiting. From the botanicals: soy may cause bloating, constipation, diarrhea, and nausea; milk thistle may cause gastrointestinal upset; black cohosh may cause dizziness or headache; motherwort may cause diarrhea or stomach irritation. Most people tolerate it well, but if you experience persistent stomach upset, stop and talk with your pharmacist.
Why can't you check the chaste extract?
We don't hold interaction data on file for standardized chaste extract, so we're unable to tell you whether it interacts with medications. That doesn't mean it's safe or unsafe—it just means we can't assess it. If you take medications, ask your pharmacist about chaste specifically.

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

Not sure if Herbal Female Complex 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.

Herbal Female Complex label
Go deeper

The Full Monographs Behind Herbal Female Complex’s Ingredients

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

Herb & supplement monograph

Iron

Interacts with 80 drugs

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventing iron deficiency and iron-deficiency an...

Read the full Iron monograph → Herb & supplement monograph

Astragalus

Interacts with 208 drugs

Astragalus is a root used for centuries in traditional Chinese medicine, mainly to support the immune system and help the body cope with stress. While early studies are interesting, strong h...

Read the full Astragalus monograph → Herb & supplement monograph

Dong Quai

Interacts with 163 drugs

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

Read the full Dong Quai monograph → Herb & supplement monograph

Soy

Interacts with 611 drugs

Soy is a nutritious bean that is a staple food and a popular source of plant protein and isoflavones. Eating soy foods as part of a balanced diet is generally considered safe for most people...

Read the full Soy 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

Black Cohosh

Interacts with 652 drugs

Black cohosh is a North American plant most often used to ease menopause symptoms like hot flashes, but the research is mixed and far from settled. It is generally well tolerated for short-t...

Read the full Black Cohosh monograph → Herb & supplement monograph

Motherwort

Interacts with 248 drugs

Motherwort is a traditional herb in the mint family long used for anxiety, heart palpitations, and women's reproductive complaints, but solid human evidence is very limited. It should be avo...

Read the full Motherwort monograph →
Sources

Sources & How We Checked

Herbal Female Complex'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 335 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.

Iron 72 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Bruner AB, Joffe A, Duggan AK, et al. Randomized study of cognitive effects of iron supplementation in non- anaemic iron-deficient adolescent girls. Lancet 1996;348:992-6.
  3. Ullen H, Augustsson K, Gustavsson C, Steineck G. Supplementary iron intake and risk of cancer: reversed causality? Cancer Lett 1997;114:215-6.
  4. Reunanen A, Takkunen H, Knekt P, et al. Body iron stores, dietary iron intake and coronary heart disease mortality. J Intern Med 1995;238:223-30. PubMed
  5. Lund EK, Wharf SG, Fairweather-Tait SJ, Johnson IT. Oral ferrous sulfate supplements increase the free radical-generating capacity of feces from healthy volunteers. Am J Clin Nutr 1999;69:250-5.
  6. Rehman A, Collis CS, Yang M, et al. The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers. Biochem Biophys Res Comm 1998;246:293-8. PubMed
  7. Klipstein-Grobusch K, Grobbee DE, den Breeijen JH, et al. Dietary iron and risk of myocardial infarction in the Rotterdam Study. Am J Epidemiol 1999;149:421-8. PubMed
  8. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  9. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  10. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  11. Campbell N, Paddock V, Sundaram R. Alteration of methyldopa absorption, metabolism, and blood pressure control by ferrous sulfate and ferrous gluconate. Clin Pharmacol Ther 1988;43:381-6..
  12. Schumann K, Borch-Iohnsen B, Hentze MW, Marx JJ. Tolerable upper intakes for dietary iron set by the US Food and Nutrition Board (commentary). Am J Clin Nutr 2002;76:499-500. PubMed
  13. Tuomainen TP, Punnonen K, Nyyssonen K, Salonen JT. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation 1998;97:1461-6.. PubMed
  14. Salonen JT, Nyyssonen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men. Circulation 1992;86:803-11.. PubMed
  15. Campbell NRC, Hasinoff B. Ferrous sulfate reduces levodopa bioavailability: Chelation as a possible mechanism. Clin Pharmacol Ther 1989;45:220-5.. PubMed
  16. Campbell NRC, Hasinoff BB, Stalts H, et al. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Int Med 1992;117:1010-3.. PubMed
  17. Kiechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 1997;96:3300-07. PubMed
  18. Comparison of oral iron supplements. Pharmacist's Letter / Prescriber's Letter 2008;24(8):240811.
  19. Tran T., Wax J. R., Philput C., Steinfeld J. D., Ingardia C. J. Intentional iron overdose in pregnancy--management and outcome. J Emerg Med 2000;18(2):225-228. PubMed
  20. Toblli J. E., Brignoli, R. Iron(III)-hydroxide polymaltose complex in iron deficiency anemia / review and meta-analysis. Arzneimittelforschung 2007;57(6A):431-438. PubMed
  21. Köpcke W., Sauerland M. C. Meta-analysis of efficacy and tolerability data on iron proteinsuccinylate in patients with iron deficiency anemia of different severity. Arzneimittelforschung 1995;45(11):1211-1216.
  22. Campbell N. R., Campbell R. R., Hasinoff B. B. Ferrous sulfate reduces methyldopa absorption: methyldopa: iron complex formation as a likely mechanism. Clin Invest Med 1990;13(6):329-332.
  23. Morii M., Ueno K., Ogawa A., Kato R., Yoshimura H., Wada K., Hashimoto H., Takada M., Tanaka K., Nakatani T., Shibakawa M. Impairment of mycophenolate mofetil absorption by iron ion. Clin Pharmacol Ther 2000;68(6):613-616. PubMed
  24. Gelone D. K., Park J. M., Lake K. D. Lack of an effect of oral iron administration on mycophenolic acid pharmacokinetics in stable renal transplant recipients. Pharmacotherapy 2007;27(9):1272-1278. PubMed
  25. Ducray P. S., Banken L., Gerber M., Boutouyrie B., Zandt H. Absence of an interaction between iron and mycophenolate mofetil absorption. Br J Clin Pharmacol 2006;62(4):492-495. PubMed
  26. Lorenz M., Wolzt M., Weigel G., Puttinger H., Hörl W. H., Födinger M., Speiser W., Sunder-Plassmann G. Ferrous sulfate does not affect mycophenolic acid pharmacokinetics in kidney transplant patients. Am J Kidney Dis 2004;43(6):1098-1103. PubMed
  27. Osman M. A., Patel R. B., Schuna A., Sundstrom W. R., Welling P. G. Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate. Clin Pharmacol Ther 1983;33(4):465-470. PubMed
  28. Michael, B., Coyne, D. W., Fishbane, S., Folkert, V., Lynn, R., Nissenson, A. R., Agarwal, R., Eschbach, J. W., Fadem, S. Z., Trout, J. R., Strobos, J., and Warnock, D. G. Sodium ferric gluconate complex in hemodialysis patients: adverse reactions compar
  29. Zhang, X., Ouyang, J., Wieczorek, R., and DeSoto, F. Iron medication-induced gastric mucosal injury. Pathol.Res Pract 2009;205(8):579-581. PubMed
  30. Barbieri, P. G. [To-day exposure to occupational carcinogens and their effects. The experience of the rubber industry, iron metallurgy, asphalt work and aviculture]. Epidemiol.Prev 2009;33(4-5 Suppl 2):94-105.
  31. Macedo, A. and Cardoso, S. [Routine iron supplementation in pregnancy]. Acta Med Port. 2010;23(5):785-792.
  32. Bastide, N. M., Pierre, F. H., and Corpet, D. E. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res (Phila) 2011;4(2):177-184. PubMed
  33. Stevens, R. G. Iron and the risk of cancer. Med Oncol Tumor Pharmacother. 1990;7(2-3):177-181. PubMed
  34. van den, Hombergh J., Dalderop, E., and Smit, Y. Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania. J.Trop.Pediatr. PubMed
  35. Liabeuf S, Gras V, Moragny J, et al. Ulceration of the oral mucosa following direct contact with ferrous sulfate in elderly patients: a case report and a review of the French National Pharmacovigilance Database. Clin Interv Aging. 2014 Apr 25;9:737-40. PubMed
  36. Qiao L, Feng Y. Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies. Cancer Causes Control. 2013 Jun;24(6):1175-83. PubMed
  37. 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
  38. 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
  39. Song I, Borland J, Arya N, Wynne B, Piscitelli S. Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. J Clin Pharmacol. 2015;55(5):490-6. PubMed
  40. Esan MO, Boele van Hensbroek M, Nkhoma E, et al. Iron supplementation in HIV infected Malawian children with anemia: a double-blind, randomized, controlled trial. Clin Inf Dis 2013;57(11):1626-34.doi:10.1093/cid/cit528. PubMed
  41. Zlotkin S, Newton S, Aimone AM, et al. Effect of iron fortification on malaria incidence in infants and young children in Ghana: a randomized trial. JAMA 2013;310(9):938-47. PubMed
  42. Khambalia AZ, Aimone A, Nagubandi P, et al. High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: a prospective study and systematic review. Diabet Med. 2016;33(9):1211-21. PubMed
  43. Kinnunen TI, Luoto R, Helin A, Hemminki E. Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland. Matern Child Nutr. 2016;12(1):74-84.
  44. Low MS, Speedy J, Styles CE, De-Regil LM, Pasricha SR. Daily iron supplementation for improving anaemia, iron status and health in menstruating women. Cochrane Database Syst Rev. 2016;4:CD009747. PubMed
  45. Melit LE, Marginean CO, Mocanu S, Marginean MO. A rare case of iron-pill induced gastritis in a female teenager: A case report and a review of the literature. Medicine (Baltimore). 2017;96(30):e7550. PubMed
  46. Neuberger A, Okebe J, Yahav D, Paul M. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2016;2:CD006589. PubMed
  47. Peña-Rosas JP, De-Regil LM, Gomez Malave H, Flores-Urrutia MC, Dowswell T. Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015;(10):CD009997. PubMed
  48. Brabin B, Gies S, Roberts SA, et al. Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso. Mala PubMed
  49. Kaundal R, Bhatia P, Jain A, et al. Randomized controlled trial of twice-daily versus alternate-day oral iron therapy in the treatment of iron-deficiency anemia. Ann Hematol 2020;99(1):57-63. PubMed
  50. Li N, Zhao G, Wu W, et al. The efficacy and safety of vitamin C for iron supplementation in adult patients with iron deficiency anemia: A randomized clinical trial. JAMA Netw Open. 2020;3(11):e2023644.<br> PubMed
  51. Houston BL, Hurrie D, Graham J, et al. Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials. BMJ Open. 2018;8(4):e019240. PubMed
  52. Koch RM, Tchernodrinski S, Principe DR. Case report: Rapid onset, ischemic-type gastritis after initiating oral iron supplementation. Front Med (Lausanne) 2022;9:1010897. PubMed
  53. Milman NT. Iron supplementation in pregnant Danish women revisited: Effects on prepartum and postpartum iron deficiency, anemia, serum erythropoietin; including iron status, erythropoietin and anthropometrics in newborns. A randomized, placebo-controlled
  54. Rogozinska E, Daru J, Nicolaides M, et al. Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis. Lancet Haematol 2021;8(7):e503-e512. PubMed
  55. Shah AA, Donovan K, Seeley C, et al. Risk of infection associated with administration of intravenous iron: A systematic review and meta-analysis. JAMA Netw Open 2021;4(11):e2133935. PubMed
  56. Gamad N, Saha PK, Sharma P, Suri V, Chakrabarti A, Saha L. A randomized controlled trial comparing the efficacy, tolerability, and cost of oral iron preparations in iron-deficiency anemia in pregnancy. J Obstet Gynaecol Res 2021;47(11):3828-3841. PubMed
  57. El-Hawy MA, Abd Al-Salam SA, Bahbah WA. Comparing oral iron bisglycinate chelate, lactoferrin, lactoferrin with iron and iron polymaltose complex in the treatment of children with iron deficiency anemia. Clin Nutr ESPEN 2021;46:367-371. PubMed
  58. Adams A, Scheckel B, Habsaoui A, et al. Intravenous iron versus oral iron versus no iron with or without erythropoiesis- stimulating agents (ESA) for cancer patients with anaemia: a systematic review and network meta-analysis. Cochrane Database Syst Rev 2 PubMed
  59. Kancherla K, Constantin H, Kanawati A, Graham E. Iron-induced Hypophosphatemic Osteomalacia-An Atypical Case of Bilateral Femoral Stress Fractures. J Am Acad Orthop Surg Glob Res Rev 2023;7(5):e22. PubMed
  60. Shi R, Marin JG, Beaulieu M. Skin staining following intravenous iron extravasation in a patient with chronic kidney disease: A case report. Can J Kidney Health Dis 2023;10:20543581231165705. PubMed
  61. Varandas C, Vieira J, Correia CJ, et al. Hypersensitivity reactions to iron products: 10-year experience in a Portuguese tertiary Centre. Eur Ann Allergy Clin Immunol 2023.
  62. Jara Vidal M, López García MC, Quílez Toboso RP. Kounis syndrome after intravenous iron administration. Med Clin (Barc) 2023. DOI
  63. Jara Vidal M, Ruiz de Assín Valverde A, Aznar Rodríguez S. Severe hypophospathemia secondary to intravenous iron. Med Clin (Barc) 2023. DOI
  64. Samões B, Silva B, Martins A, et al. Hypophosphatemic osteomalacia induced by intravenous iron therapy: a case report. Joint Bone Spine 2023;90(5):105586. PubMed
  65. Seng NW, Barco JB, Wong MH, et al. Hypophosphatemia related to intravenous iron therapy with ferric carboxymaltose: A case series. Transfus Med 2023. PubMed
  66. Fernandez-Flores A, Fernandez-Parrado M, Alzoghby-Abi Chaker J, Angulo AG. Axillary cutaneous hemosiderosis in a patient with hyperhidrosis, after intravenous iron infusion. Am J Dermatopathol 2023;45(7):463-465. PubMed
  67. Ye S, Grill V, Luo J, Nguyen HH. Concurrent Denosumab and Parenteral Iron Therapy Precipitating Severe Hypocalcemia and Hypophosphatemia. JCEM Case Rep 2024;2(2):luae005. PubMed
  68. Yerigeri K. Hemochromatosis in an Adult Female With Previous Iron Deficiency Anemia on Iron Supplementation. Cureus 2023;15(12):e50166. PubMed
  69. Meyers M, Salmon M, Libert I, Klá&scaron;terský J. A meta-analysis on the risk of infection associated with intravenous iron therapy in cancer-associated anaemia: a double-edged sword?. Curr Opin Oncol 2024;36(4):223-232. PubMed
  70. Short V, Allen R, Earley CJ, et al. A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia. Am J Hem PubMed
  71. Bellos I, Frountzas M, Pergialiotis V. Comparative Risk of Hypophosphatemia Following the Administration of Intravenous Iron Formulations: A Network Meta-Analysis. Transfus Med Rev 2020;34(3):188-194. PubMed
  72. 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 Iron monograph →

Astragalus 13 references
  1. Upton R, ed. Astragalus Root: Analytical, quality control, and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia. 1999:1-25.
  2. Khoo KS, Ang PT. Extract of astragalus membranaceus and ligustrum lucidum does not prevent cyclophosphamide-induced myelosuppression. Singapore Med J 1995;36:387-90.
  3. Chu DT, Wong WL, Mavligit GM. Immunotherapy with Chinese medicinal herbs. II. Reversal of cyclophosphamide-induced immune suppression by administration of fractionated Astragalus membranaceus in vivo. J Clin Lab Immunol 1988;25:125-9.
  4. Sun Y, Hersh EM, Lee SL, et al. Preliminary observations on the effects of the Chinese medicinal herbs Astragalus membranaceus and Ligustrum lucidum on lymphocyte blastogenic responses. J Biol Response Mod 1983;2:227-37..
  5. Ma J, Peng A, Lin S. Mechanisms of the therapeutic effect of astragalus membranaceus on sodium and water retention in experimental heart failure. Chin Med J (Engl) 1998;111:17-23.
  6. Matkovic Z, Zivkovic V, Korica M, et al. Efficacy and safety of Astragalus membranaceus in the treatment of patients with seasonal allergic rhinitis. Phytother Res 2010;24:175-81.
  7. Zhang, J. G., Yang, N., He, H., Wei, G. H., Gao, D. S., Wang, X. L., Wang, X. Z., and Song, G. Y. [Effect of Astragalus injection on plasma levels of apoptosis-related factors in aged patients with chronic heart failure.]. Chin J Integr.Med 2005;11(3):18 PubMed
  8. Chen, H. W., Lin, I. H., Chen, Y. J., Chang, K. H., Wu, M. H., Su, W. H., Huang, G. C., and Lai, Y. L. A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study. Clin Invest PubMed
  9. Tian H, Lu J, He H, et al.The effect of Astragalus as an adjuvant treatment in type 2 diabetes mellitus: A (preliminary) meta-analysis. J Ethnopharmacol. 2016;191:206-215. doi: 10.1016/j.jep.2016.05.062. PubMed
  10. Hong KF, Liu PY, Zhang W, Gui DK, Xu YH. The Efficacy and Safety of Astragalus as an Adjuvant Treatment for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Integr Complement Med 2023. PubMed
  11. Chan KW, Kwong ASK, Tsui PN, et al. Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial. Phytomedicine 2024;130:155457. PubMed
  12. Han X, Yu T, Chen X, Du Z, Yu M, Xiong J. Effect of Astragalus membranaceus on left ventricular remodeling in HFrEF: a systematic review and meta-analysis. Front Pharmacol 2024;15:1345797. PubMed
  13. Jing P, Hongzheng H, Zhenqi WU, Meijuan Z, Zuojing LI, Gang C. Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials. J Tradit Chin Med 2024;44(2):

See these in context on the Astragalus monograph →

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

See these in context on the Dong Quai monograph →

Soy 88 references
  1. Franke AA, Custer LJ, Tanaka Y. Isoflavones in human breast milk and other biological fluids. Am J Clin Nutr 1998;68:1466-73. PubMed
  2. Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 1998;91:6-11. PubMed
  3. Lu LJ, Anderson KE, Grady JJ, et al. Decreased ovarian hormones during a soya diet: implications for breast cancer prevention. Cancer Res 2000;60:4112-21.
  4. Pino AM, Valladares LE, Palma MA, et al. Dietary isoflavones affect sex hormone-binding globulin levels in postmenopausal women. J Clin Endocrinol Metab 2000;85:2797-800. DOI
  5. Nisley N, Klepser T. Phytoestrogens for the prevention and treatment of osteoporosis. Alt Med Alert 1999 Dec;138-42.
  6. McMichael-Phillips DF, Harding C, Morton M, et al. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr 1998;68:1431S-5S. PubMed
  7. Petrakis NL, Barnes S, King EB, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomarkers Prev 1996;5:785-94.
  8. Baird DD, Umbach DM, Lansdell L, et al. Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women. J Clin Endocrinol Metab 1995;80:1685-90. DOI
  9. Duncan AM, Underhill KE, Xu X, et al. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab 1999;84:3479-84. PubMed
  10. Ginsburg J, Prelevic GM. Lack of significant hormonal effects and controlled trials of phyto-oestrogens. Lancet 2000;355:163-4. PubMed
  11. Anthony MS. Soy and cardiovascular disease: Cholesterol lowering and beyond. J Nutr 2000;130:662S-3S. PubMed
  12. Hargreaves DF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 1999;84:4017-24. DOI
  13. Lamartiniere CA. Protection against breast cancer with genistein: a component of soy. Am J Clin Nutr 2000;71:1705S-7S. PubMed
  14. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
  15. Codina R, Ardusso L, Lockey RF, et al. Sensitization to soybean hull allergens in subjects exposed to different levels of soybean dust inhalation in Argentina. J Allergy Clin Immunol 2000;105:570-6. PubMed
  16. Anto JM, Sunyer J, Rodriguez-Roisin R, et al. Community outbreaks of asthma associated with inhalation of soybean dust. Toxicoepidemiological Committee. N Engl J Med 1989;320:1097-1102. PubMed
  17. White MC, Etzel RA, Olson DR, Goldstein IF. Re-examination of epidemic asthma in New Orleans, Louisianna, in relation to the presence of soy at the harbor. Am J Epidemiol 1997;145:432-8.
  18. Murkies A, Dalais FS, Briganti EM, et al. Phytoestrogens and breast cancer in postmenopausal women: a case control study. Menopause 2000;7:289-96. PubMed
  19. Setchell KD, Cassidy A. Dietary isoflavones: biological effects and relevance to human health. J Nutr 1999;129:758S-67S. PubMed
  20. Teixeira SR, Potter SM, Weigel R, et al. Effects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men. Am J Clin Nutr 2000;71:1077-84. PubMed
  21. White LR, Petrovitch H, Ross GW, et al. Brain aging and midlife tofu consumption. J Am Coll Nutr 2000;19:242-55. PubMed
  22. Grodstein F, Mayeux R, Stampfer MJ. Tofu and cognitive function: food for thought. J Am Coll Nutr 2000;19:207-9. PubMed
  23. Divi RL, Chang HC, Doerge DR. Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol 1997;54:1087-96. PubMed
  24. de Lemos ML. Effects of soy phytoestrogens genistein and daidzein on breast cancer growth. Ann Pharmacother 2001;35:1118-21. PubMed
  25. Strom BL, Schinnar R, Ziegler EE, et al. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 2001;286:807-14. PubMed
  26. Goodman MT, Wilkens LR, Hankin JH, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol 1997;146:294-306. PubMed
  27. Wu AH, Yang D, Pike MC. A meta-analysis of soyfoods and risk of stomach cancer: the problem of potential confounders. Cancer Epidemiol Biomarkers Prev 2000;9:1051-8.
  28. Ji BT, Chow WH, Yang G, et al. Correspondence re: AH Wu et al, A meta-analysis of soyfoods and risk of stomach cancer: the problem of potential confounders. Cancer Epidemiol Biomarkers Prev 2001;10:570.
  29. Foth D, Cline JM. Effects of mammalian and plant estrogens on mammary glands and uteri of macaques. Am J Clin Nutr 1998;68:1413S-7S. PubMed
  30. Duncan AM, Merz BE, Xu X, et al. Soy isoflavones exert modest hormonal effects in premenopausal women. J Clin Endocrinol Metab 1999;84:192-7. DOI
  31. Morito K, Hirose T, Kinjo J, et al. Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol Pharm Bull 2001;24:351-6. PubMed
  32. Persky VW, Turyk ME, Wang L, et al. Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr 2002;75:145-53. PubMed
  33. Ju YH, Doerge DR, Allred KF, et al. Dietary Genistein Negates the Inhibitory Effect of Tamoxifen on Growth of Estrogen-dependent Human Breast Cancer (MCF-7) Cells Implanted in Athymic Mice. Cancer Res 2002;62:2474-7 .
  34. Cambria-Kiely JA. Effect of soy milk on warfarin efficacy. Ann Pharmacother 2002;36:1893-6.. PubMed
  35. Ziegler RG, Hoover RN, Pike MC, et al. Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst 1993;85:1819-27.. PubMed
  36. Brown BD, Thomas W, Hutchins A, et al. Types of dietary fat and soy minimally affect hormones and biomarkers associated with breast cancer risk in premenopausal women. Nutr Cancer 2002;43:22-30.. PubMed
  37. Sun CL, Yuan JM, Arakawa K, et al. Dietary soy and increased risk of bladder cancer: the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev 2002;11:1674-7.
  38. Balk JL, Whiteside DA, Naus G, et al. A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium. J Soc Gynecol Investig 2002;9:238-42.. DOI
  39. Horn-Ross PL, John EM, Canchola AJ, et al. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 2003;95:1158-64.. PubMed
  40. Kumar NB, Cantor A, Allen K et al. The specific role of isoflavones in reducing prostate cancer risk. Prostate 2004;59:141-7. PubMed
  41. Chen A, Rogan WJ. Isoflavones in soy infant formula: a review of evidence for endocrine and other activity in infants. Annu Rev Nutr 2004;24:33-54. PubMed
  42. Chen YM, Ho SC, Lam SS, et al. Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003;88:4740-7. PubMed
  43. Unfer V, Casini ML, Costabile L, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertil Steril 2004;82:145-8. PubMed
  44. Bruce B, Messina M, Spiller G. Isoflavone supplements do not affect thyroid function in iodine-replete postmemopausal women. J Med Food 2003;6:309-16.
  45. He J, Gu D, Wu X, et al. Effect of soybean protein on blood pressure: A randomized, controlled trial. Ann Intern Med 2005;143:1-9. PubMed
  46. Kaari C, Haidar MA, Junior JMS, et al. Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: a pilot study. Maturitas 2006;53:49-58. PubMed
  47. Sacks FM, Lichtenstein A, Van Horn L, et al. Soy protein, isoflavones, and cardiovascular health. An American Heart Association Science Advisory for Professionals from the Nutrition Committee. Circulation 2006;113:1034-44. PubMed
  48. Jones JL, Daley BJ, Enderson BL, et al. Genistein inhibits tamoxifen effects on cell proliferation and cell cycle arrest in T47D breast cancer cells. Am Surg 2002;68:575-7. DOI
  49. Shulman KI, Walker SE. Refining the MAOI diet: tyramine content of pizzas and soy products. J Clin Psychiatry 1999;60:191-3. DOI
  50. Gardner DM, Shulman KI, Walker SE, Tailor SA. The making of a user friendly MAOI diet. J Clin Psychiatry 1996;57:99-104.
  51. Walker SE, Shulman KI, Tailor SA, Gardner D. Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets. J Clin Psychopharmacol 1996;16:383-8. PubMed
  52. Krebs EE, Ensrud KE, MacDonald R, Wilt TJ. Phytoestrogens for treatment of menopausal symptoms: a systematic review. Obstet Gynecol 2004;104:824-36. PubMed
  53. Wang G, Xiao CQ, Li Z, et al. Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers. Ann Pharmacother 2009;43:1045-9. PubMed
  54. Jabbar MA, Larrea J, Shaw RA. Abnormal thyroid function tests in infants with congenital hypothyroidism: the influence of soy-based formula. J Am Coll Nutr. 1997;16(3):280-2. PubMed
  55. Conrad SC, Chiu H, Silverman BL. Soy formula complicates management of congenital hypothyroidism. Arch Dis Child. 2004;89(1):37-40. PubMed
  56. Chen, Y., Xiao, C. Q., He, Y. J., Chen, B. L., Wang, G., Zhou, G., Zhang, W., Tan, Z. R., Cao, S., Wang, L. P., and Zhou, H. H. Genistein alters caffeine exposure in healthy female volunteers. Eur.J Clin.Pharmacol. 2011;67(4):347-353. PubMed
  57. Whelan, A. M., Jurgens, T. M., and Naylor, H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can.J.Clin.Pharmacol. 2009;16(3):e407-e429.
  58. Lydeking-Olsen, E., Beck-Jensen, J. E., Setchell, K. D., and Holm-Jensen, T. Soymilk or progesterone for prevention of bone loss--a 2 year randomized, placebo-controlled trial. Eur.J Nutr. 2004;43(4):246-257. PubMed
  59. Hill, D. J., Heine, R. G., Cameron, D. J., Francis, D. E., and Bines, J. E. The natural history of intolerance to soy and extensively hydrolyzed formula in infants with multiple food protein intolerance. J.Pediatr. 1999;135(1):118-121. PubMed
  60. Fitzpatrick, M. Soy formulas and the effects of isoflavones on the thyroid. N.Z.Med J 2-11-2000;113(1103):24-26.
  61. Li, Z., Hong, K., Saltsman, P., DeShields, S., Bellman, M., Thames, G., Liu, Y., Wang, H. J., Elashoff, R., and Heber, D. Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on w
  62. Post-Skagegard, M., Vessby, B., and Karlstrom, B. Glucose and insulin responses in healthy women after intake of composite meals containing cod-, milk-, and soy protein. Eur J Clin Nutr 2006;60(8):949-954. PubMed
  63. Mclachlan, J. A., Simpson, E., and Martin, M. Endocrine disrupters and female reproductive health. Best.Pract Res Clin Endocrinol.Metab 2006;20(1):63-75. PubMed
  64. Messina, M. and Redmond, G. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature. Thyroid 2006;16(3):249-258. PubMed
  65. Rozman, K. K., Bhatia, J., Calafat, A. M., Chambers, C., Culty, M., Etzel, R. A., Flaws, J. A., Hansen, D. K., Hoyer, P. B., Jeffery, E. H., Kesner, J. S., Marty, S., Thomas, J. A., and Umbach, D. NTP-CERHR expert panel report on the reproductive and dev
  66. Azadbakht, L., Kimiagar, M., Mehrabi, Y., Esmaillzadeh, A., Padyab, M., Hu, F. B., and Willett, W. C. Soy inclusion in the diet improves features of the metabolic syndrome: a randomized crossover study in postmenopausal women. Am J Clin Nutr 2007;85(3):7 PubMed
  67. Berseth, C. L., Johnston, W. H., Stolz, S. I., Harris, C. L., and Mitmesser, S. H. Clinical response to 2 commonly used switch formulas occurs within 1 day. Clin.Pediatr.(Phila) 2009;48(1):58-65. PubMed
  68. Altorf-van der Kuil, W., Engberink, M. F., Brink, E. J., van Baak, M. A., Bakker, S. J., Navis, G., van, 't, V, and Geleijnse, J. M. Dietary protein and blood pressure: a systematic review. PLoS.One. 2010;5(8):e12102. PubMed
  69. Clement, Y. N., Onakpoya, I., Hung, S. K., and Ernst, E. Effects of herbal and dietary supplements on cognition in menopause: a systematic review. Maturitas 2011;68(3):256-263. PubMed
  70. Liu, Z. M., Chen, Y. M., and Ho, S. C. Effects of soy intake on glycemic control: a meta-analysis of randomized controlled trials. Am.J.Clin.Nutr. 2011;93(5):1092-1101. PubMed
  71. Iyngkaran, N., Yadav, M., Looi, L. M., Boey, C. G., Lam, K. L., Balabaskaran, S., and Puthucheary, S. D. Effect of soy protein on the small bowel mucosa of young infants recovering from acute gastroenteritis. J Pediatr.Gastroenterol.Nutr 1988;7(1):68-75. DOI
  72. Freni-Titulaer, L. W., Cordero, J. F., Haddock, L., Lebron, G., Martinez, R., and Mills, J. L. Premature thelarche in Puerto Rico. A search for environmental factors. Am.J Dis.Child 1986;140(12):1263-1267. PubMed
  73. Halpin, T. C., Byrne, W. J., and Ament, M. E. Colitis, persistent diarrhea, and soy protein intolerance. J Pediatr. 1977;91(3):404-407. PubMed
  74. Chorazy, P. A., Himelhoch, S., Hopwood, N. J., Greger, N. G., and Postellon, D. C. Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature. Pediatrics 1995;96(1 Pt 1):148-150. DOI
  75. Gimenez, I., Martinez, R. M., Lou, M., Mayoral, J. A., Garay, R. P., and Alda, J. O. Salidiuretic action by genistein in the isolated, perfused rat kidney. Hypertension 1998;31(2):706-711. PubMed
  76. Van Wyk JJ, Arnold MB, Wynn J, and et al. The effects of a soybean product on thyroid function in humans. Pediatrics 1959;24:752-760. DOI
  77. Fruzza AG, Demeterco-Berggren C, Jones KL. Unawareness of the effects of soy intake on the management of congenital hypothyroidism. Pediatrics. 2012;130(3):e699-702. PubMed
  78. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Risk assessment for peri- and post-menopausal women taking food supplements containing isolated isoflavones. EFSA J. 2015;13(10):4246. DOI
  79. Vitolins MZ, Griffin L, Tomlinson WV, et al. Randomized trial to assess the impact of venlafaxine and soy protein on hot flashes and quality of life in men with prostate cancer. J Clin Oncol. 2013;31(32):4092-8. PubMed
  80. Persiani S, Sala F, Manzotti C, et al. Evaluation of levothyroxine bioavailability after oral administration of a fixed combination of soy isoflavones in post-menopausal female volunteers. Drug Res (Stuttg). 2016;66(3):136-40. PubMed
  81. Wu AH, Spicer D, Garcia A, et al. Double-blind randomized 12-month soy intervention had no effects on breast MRI fibroglandular tissue density or mammographic density. Cancer Prev Res (Phila). 2015;8(10):942-51. PubMed
  82. Yagami A, Suzuki K, Nakamura M, et al. Case of anaphylactic reaction to soy following percutaneous sensitization by soy-based ingredients in cosmetic products. J Dermatol. 2015;42(9):917-8. PubMed
  83. Zhang XM, Zhang YB, Chi MH. Soy protein supplementation reduces clinical indices in type 2 diabetes and metabolic syndrome. Yonsei Med J. 2016;57(3):681-9. PubMed
  84. Barni S, Mori F, Pantano S, Novembre E. Adverse reaction to benzathine benzylpenicillin due to soy allergy: a case report. J Med Case Rep. 2015;9:134. PubMed
  85. Gao M, Wang H. Frequent milk and soybean consumption are high risks for uterine leiomyoma: A prospective cohort study. Medicine (Baltimore). 2018;97(41):e12009. PubMed
  86. Upson K, Sathyanarayana S, Scholes D, Holt VL. Early-life factors and endometriosis risk. Fertil Steril. 2015;104(4):964-971.e5. PubMed
  87. Mumford SL, Weck J, Kannan K, Buck Louis GM. Urinary phytoestrogen concentrations are not associated with incident endometriosis in premenopausal women. J Nutr. 2017;147(2):227-234. PubMed
  88. Yamagiwa Y, Sawada N, Shimazu T, et al. Soy Food Intake and Pancreatic Cancer Risk: The Japan Public Health Center-based Prospective Study. Cancer Epidemiol Biomarkers Prev. 2020;29(6):1214-1221. PubMed

See these in context on the Soy 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 →

Black Cohosh 68 references
  1. McFarlin BL, Gibson MH, O'Rear J, Harman P. A national survey of herbal preparation use by nurse-midwives for labor stimulation. Review of the literature and recommendations for practice. J Nurse Midwifery 1999;44:205-16. PubMed
  2. Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2002;177:440-3. PubMed
  3. Pepping J. Black cohosh: Cimicifuga racemosa. Am J Health Syst Pharm 1999;56:1400-2. PubMed
  4. Liske E. Therapeutic efficacy and safety of Cimicifuga racemosa for gynecologic disorders. Adv Ther 1998;15:45-53.
  5. Kruse SO, Lohning A, Pauli GF, et al. Fukiic and piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid. Planta Med 1999;65:763-4.
  6. Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19:2739-45. PubMed
  7. Gunn TR, Wright IM. The use of black and blue cohosh in labour. N Z Med J 1996;109:410-1.
  8. Baillie N, Rasmussen P. Black and blue cohosh in labour. N Z Med J 1997;110:20-1.
  9. Lontos S, Jones RM, Angus PW, Gow PJ. Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust 2003;179:390-1.. DOI
  10. Wuttke W, Seidlova-Wuttke D, Gorkow C. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas 2003;44:S67-77. PubMed
  11. Huntley A, Ernst E. A systematic review of the safety of black cohosh. Menopause 2003;10:58-64.. DOI
  12. Cohen SM, O'Connor AM, Hart J, et al. Autoimmune hepatitis associated with the use of black cohosh: a case study. Menopause 2004;11:575-7. PubMed
  13. Vitetta L, Thomsen M, Sali A. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2003;178:411-2.. PubMed
  14. Thomsen M, Vitetta L, Schmidt M, Sali A. Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust 2004;180:598-600.. DOI
  15. Cohen B, Schardt D. Center for Science in the Public Interest. Letter to Food and Drug Administration. Commissioner Mark McClellan, MD, PhD. March 4, 2004.
  16. Seidlova-Wuttke D, Hesse O, Jarry H, et al. Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta. Eur J Endocrinol 2003;149:351-62. PubMed
  17. Rockwell S, Liu Y, Higgins SA. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res Treat 2005;90:233-9. PubMed
  18. Levitsky J, Alli TA, Wisecarver J, Sorrell MF. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 2005;50:538-9. PubMed
  19. Cheong JL, Bucknall R. Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient. Postgrad Med J 2005;81:266-7.. PubMed
  20. Nappi RE, Malavasi B, Brundu B, Facchinetti F. Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol. Gynecol Endocrinol 2005;20:30-5.
  21. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  22. Minciullo PL, Saija A, Patafi M, et al. Muscle damage induced by black cohosh (Cimicifuga racemosa). Phytomedicine 2006;13:115-8. PubMed
  23. Wuttke W, Gorkow C, Seidlova-Wuttke D. Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study. Men PubMed
  24. MHRA. Black cohosh (Cimicifuga racemosa) - risk of liver problems. Herbal Safety News July 2006. Available at: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary= true&ssDocName=CON2024131&ssTargetNodeId=663.
  25. Dugoua JJ, Seely D, Perri D, et al. Safety and efficacy of black cohosh (cimicifuga racemosa) during pregnancy and lactation. Can J Clin Pharmacol 2006;13:e257-61.
  26. Raus K, Brucker C, Gorkow C, Wuttke W. First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055. Menopause 2006;13:678-91. PubMed
  27. Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl 2006;12:989-92. PubMed
  28. Bai W, Henneicke-von Zepelin HH, Wang S, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: A randomized, double blind, parallel-controlled study versus tibol
  29. Meyer S, Vogt T, Obermann EC, et al. Cutaneous pseudolymphoma induced by Cimicifuga racemosa. Dermatology 2007;214:94-6.
  30. Gori L, Firenzuoli F. Is black cohosh a hepatotoxic medicinal herb? Forsch Komplementarmed 2007;14:109-10. PubMed
  31. Assessment of case reports connected to herbal medicinal products containing cimicifugae racemosa rhizoma (black cohosh, root). Doc. Ref. EMEA/269259/2006. Available at: www.emea.eu.int/pdfs/human/hmpc/26925806en.pdf (Accessed 30 November 2007).
  32. Chung DJ, Kim HY, Park KH, et al. Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J 2007;48:289-94. PubMed
  33. Chow ECY, Teo M, Ring JA, Chen JW. Liver failure associated with the use of black cohosh for menopausal symptoms. Med J Aust 2008;188:420-2. PubMed
  34. Mahady GB, Low Dog T, Barrett ML, et al. United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause 2008;15:628-38. PubMed
  35. Hepatotoxicity with black cohosh. Australian Adv Drug Reactions Bull 2006;25:6. Available at: www.tga.gov.au/adr/aadrb/aadr0604.htm#a1.
  36. Dunbar K, Solga SF. Black cohosh, safety, and public awareness. Liver Int 2007;27:1017. PubMed
  37. Patel NM, Derkits RM. Possible increase in liver enzymes secondary to atorvastatin and black cohosh administration. J Pharm Pract 2007;20:341-6. DOI
  38. Joy D, Joy J, Duane P. Black cohosh: a cause of abnormal postmenopausal liver function tests. Climacteric 2008;11:84-8. PubMed
  39. Australian Adverse Drug Reactions Advisory Committee. Black cohosh and liver toxicity - an update. Aust Adv Drug Reactions Bull 2007;26:11.
  40. Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63.
  41. Spangler L, Newton KM, Grothaus LC, et al. The effects of black cohosh therapies on lipids, fibrinogen, glucose and insulin. Maturitas 2007;57:195-204. PubMed
  42. Teschke R, Bahre R, Genthner A, et al. Suspected black cohosh hepatotoxicity - challenges and pitfalls of causality assessment. Maturitas 2009;63:302-14. PubMed
  43. Brasky TM, Lampe JW, Potter JD, et al. Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Epidemiol Biomarkers Prev 2010;19:1696-708. PubMed
  44. Fuchikami H, Satoh H, Tsujimoto M, Ohdo S, Ohtani H, Sawada Y. Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 2006;34:577-82. PubMed
  45. Vermes G, Bánhidy F, Acs N. The effects of remifemin on subjective symptoms of menopause. Adv Ther 2005;22:148-54. PubMed
  46. Nuntanakorn, P., Jiang, B., Einbond, L. S., Yang, H., Kronenberg, F., Weinstein, I. B., and Kennelly, E. J. Polyphenolic constituents of Actaea racemosa. J Nat Prod 2006;69(3):314-318.
  47. Oktem M, Eroglu D, Karahan HB, Taskintuna N, Kuscu E, Zeyneloglu HB. Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. Adv Ther 2007;24:448-61. PubMed
  48. Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment--results of a large-scale, controlled, observational study. Maturitas 2007;57:405-14. PubMed
  49. Naser, B. and Liske, E. Liver failure associated with the use of black cohosh for menopausal symptoms. Med J Aust. 1-19-2009;190(2):99. PubMed
  50. van de Meerendonk, H. W., van Hunsel, F. P., and van der Wiel, H. E. [Autoimmune hepatitis induced by Actaea racemosa. Side affects of an herb extract]. Ned.Tijdschr.Geneeskd. 2-7-2009;153(6):246-249.
  51. Wong, V. C., Lim, C. E., Luo, X., and Wong, W. S. Current alternative and complementary therapies used in menopause. Gynecol.Endocrinol. 2009;25(3):166-174. PubMed
  52. Pierard, S., Coche, J. C., Lanthier, P., Dekoninck, X., Lanthier, N., Rahier, J., and Geubel, A. P. Severe hepatitis associated with the use of black cohosh: a report of two cases and an advice for caution. Eur J Gastroenterol Hepatol. 2009;21(8):941-945 PubMed
  53. Vannacci, A., Lapi, F., Gallo, E., Vietri, M., Toti, M., Menniti-Ippolito, F., Raschetti, R., Firenzuoli, F., and Mugelli, A. A case of hepatitis associated with long-term use of Cimicifuga racemosa. Altern.Ther Health Med 2009;15(3):62-63.
  54. Zimmermann, R., Witte, A., Voll, R. E., Strobel, J., and Frieser, M. Coagulation activation and fluid retention associated with the use of black cohosh: a case study. Climacteric. 2010;13(2):187-191. PubMed
  55. Amsterdam JD, Yao Y, Mao JJ, Soeller I, Rockwell K, Shults J. Randomized, double-blind, placebo-controlled trial of Cimicifuga racemosa (black cohosh) in women with anxiety disorder due to menopause. J Clin Psychopharmacol 2009;29:478-83. PubMed
  56. Bai WP, Wang SY, Liu JL, Geng L, Hu LN, Zhang ZL, Chen SL, Zheng SR. [Efficacy and safety of remifemin compared to tibolone for controlling of perimenopausal symptoms]. Zhonghua Fu Chan Ke Za Zhi 2009;44:597-600.
  57. McKenzie, S. C. and Rahman, A. Bradycardia in a patient taking black cohosh. Med J Aust. 10-18-2010;193(8):479-481. PubMed
  58. Stolze H. [An alternative to treat menopausal complaints]. Gynecologie 1982;1:14-16.
  59. Guzman G, Kallwitz ER, Wojewoda C, et al. Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh. Case Rep Med. 2009;2009:918156. PubMed
  60. Enbom ET, Le MD, Oesterich L, Rutgers J, French SW. Mechanism of hepatotoxicity due to black cohosh (Cimicifuga racemosa): histological, immunohistochemical and electron microscopy analysis of two liver biopsies with clinical correlation. Exp Mol Pathol. PubMed
  61. Sen A. Orobuccolingual dyskinesia after long-term use of black cohosh and ginseng. J Neuropsychiatry Clin Neurosci 2013 Fall;25(4):E50. PubMed
  62. Hoban CL, Byard RW, Musgrave IF. Analysis of spontaneous adverse drug reactions to echinacea, valerian, black cohosh and ginkgo in Australia from 2000 to 2015. J Integr Med. 2019;17(5):338-343. PubMed
  63. Pkhaladze L, Davidova N, Khomasuridze A, Shengelia R, Panossian AG. Actaea racemosa L. is more effective in combination with Rhodiola rosea L. for relief of menopausal symptoms: a randomized, double-blind, placebo-controlled study. Pharmaceuticals (Basel) PubMed
  64. Yalçin M, Oguz A, Bestepe EE, Saglam NGU, Ergelen M. Black cohosh associated mania in a patient with unipolar depression. Int J Psychiatry Med 2020 Sep 21:91217420961185. doi: 10.1177/0091217420961185. PubMed
  65. Brar HS, Marathi R. Case of cholestatic drug-induced liver injury (DILI) associated with black cohosh. BMJ Case Rep 2021;14(5):e240408. PubMed
  66. Castelo-Branco C, Navarro C, Beltrán E, Losa F, Camacho M; on the behalf of the Natural Products Study Group of the Spanish Menopause Society. Black cohosh efficacy and safety for menopausal symptoms. The Spanish Menopause Society statement. Gynecol Endoc PubMed
  67. Trant AA, Chagpar A, Wei W, et al. The Effect of Black Cohosh on Ki67 expression and Tumor Volume: A Pilot Study of Ductal Carcinoma in Situ Patients. Integr Cancer Ther 2022;21:15347354221137290. PubMed
  68. Dernbach MR, Carpenter JE, Shah N, Carter GB. Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report. J Emerg Med 2024;66(5):e592-e596. PubMed

See these in context on the Black Cohosh monograph →

Motherwort 6 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  4. Wojtyniak K, Szymanski M, Matlawska I. Leonurus cardiaca L. (motherwort): a review of its phytochemistry and pharmacology. Phytother Res 2013;27(8):1115-20.
  5. Xia WT, Zhou H, Wang Y, et al. Motherwort injection in preventing post-abortion hemorrhage after induced abortion: A multi-center, prospective, randomized controlled trial. Explore (NY). 2019. pii: S1550-8307(19)30447-1. PubMed
  6. Cao Shan DOSOGC, Zhang W, Zhao Z, et al. Post-marketing safety surveillance and reevaluation of Motherwort injection: A clinical study of 10 094 cases. J Tradit Chin Med. 2018 Aug;38(4):625-635. DOI

See these in context on the Motherwort 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