Genistein

Glycine max (primary dietary source)
Evidence Level
Moderate
3 Clinical Trials
5 Documented Benefits
3/5 Evidence Score

Genistein is the main isoflavone in soybeans and a well studied phytoestrogen. It binds estrogen receptors, with a preference for the beta subtype, which means it is hormonally active in the body. It has been studied almost entirely in postmenopausal women, for hot flushes, bone density and blood markers linked to cardiovascular risk. The human evidence here is unusually good for a plant compound: a 389 woman, 24 month randomized trial published in Annals of Internal Medicine found bone mineral density rose on 54 mg per day of genistein aglycone and fell on placebo, at both the lumbar spine and the femoral neck, with P less than 0.001. The honest caveat is that all four trials on this page come from the same research group in Messina, Italy, and no independent team has repeated them. The findings apply to women with osteopenia or in early menopause, not to men, premenopausal women or people with normal bone density.

Studied Dose The trials behind this page used 54 mg per day of genistein aglycone for 12 to 24 months, with every participant also taking calcium and vitamin D. That is far more genistein than a normal diet supplies, and all of these trials came from one Italian research group.
Active Compound Genistein aglycone, an isoflavone phytoestrogen with selective ER-beta preference.

Benefits

Helps maintain bone mineral density

In 389 postmenopausal women with osteopenia (bone density below normal but not osteoporosis), 54 mg per day of genistein aglycone for 24 months raised bone mineral density at the lumbar spine and femoral neck, while density fell in the placebo group. Both differences were highly statistically significant (P less than 0.001), and everyone in the trial also took calcium and vitamin D. This was a study in women already diagnosed with low bone density, and it comes from a single Italian centre that no other group has replicated.

Helps reduce menopausal hot flashes

In a 12 month randomized trial in early postmenopausal women, daily hot flushes fell by about 22 percent at 3 months, 29 percent at 6 months and 24 percent at 12 months compared with placebo. The benefit levelled off rather than building steadily, so 'progressive improvement' would overstate it. The study also included an estrogen-progestin therapy arm as a comparison, and it is a single trial from the same Italian group.

Supports mood and quality of life in postmenopause

In a two year randomized trial in postmenopausal women with osteopenia, those taking genistein reported better quality-of-life scores and fewer depression symptoms than those on placebo. These were self-reported questionnaire outcomes in women enrolled for a bone study, not a trial of people being treated for depression, and genistein is not a treatment for depression or any other mood disorder.

Supports cardiometabolic risk markers

A two year randomized trial in postmenopausal women with osteopenia reported changes in some blood markers used to estimate cardiovascular risk. These are laboratory measurements, not heart attacks, strokes or any other real-world event, so this does not show that genistein protects the heart or prevents heart disease. It is also the same single Italian research group as the other trials here.

Provides selective phytoestrogen activity

Genistein binds estrogen receptors and prefers the beta subtype, which is the leading explanation for its effects on bone and hot flushes in the trials above. Preferring one receptor subtype is still hormonal activity. It should not be taken as evidence that genistein is safe for breast, uterine or ovarian tissue, because none of the studies cited on this page tested that question.

Mechanism of action

1

Selective estrogen receptor beta agonism

Genistein binds estrogen receptors with higher affinity for the beta subtype than the alpha subtype. This is the proposed reason it can copy some effects of estrogen in bone and blood vessels, and it means genistein is hormonally active rather than hormone free.

2

Bone remodeling balance

In laboratory and animal work, genistein acting through the beta estrogen receptor appears to encourage the cells that build bone and quiet the cells that break it down. This is the leading explanation for the bone density results seen in the human trial, but it was not measured directly in the women who took part.

3

Tyrosine kinase and signaling modulation

In cell studies, genistein also blocks certain enzymes called tyrosine kinases and changes signaling inside cells. This is test tube biology only. None of the human trials cited on this page measured anything of the kind, and it says nothing about what genistein does to cancer in people.

4

Antioxidant and anti-inflammatory activity

In test tube and animal studies, genistein neutralizes reactive oxygen species and dampens inflammatory signaling. This is one proposed explanation for the blood marker changes seen in the cardiovascular risk trial, and it has not been confirmed as the actual mechanism in people.

Clinical trials

1
24-month bone density RCT

Multicenter, randomized, double-blind, placebo-controlled trial; 54 mg/day genistein aglycone vs placebo for 24 months, all participants receiving calcium and vitamin D.

389 osteopenic postmenopausal women with low femoral neck bone mineral density.

At 24 months bone mineral density rose on genistein and fell on placebo at both sites: lumbar spine +0.049 versus -0.053 g/cm2, and femoral neck +0.035 versus -0.037 g/cm2, both with P less than 0.001. Published in Annals of Internal Medicine, this is a large, long and well conducted trial and the strongest single piece of evidence on this page. Its main limitation is that it comes from one Italian research group and has not been independently repeated.

2
12-month hot flush RCT vs EPT and placebo

Randomized, double-blind, EPT- and placebo-controlled study; 54 mg/day genistein vs estrogen-progestin therapy vs placebo for 12 months.

90 healthy early postmenopausal women aged 47–57.

Compared with placebo, daily hot flushes fell by an average of 22% at 3 months, 29% at 6 months and 24% at 12 months in the genistein group. The benefit levelled off rather than continuing to grow. This is one trial, from the same Italian group as the bone studies, and how genistein compared with the estrogen-progestin arm is not reported here.

3
Quality-of-life and depression sub-study

Two-year randomized, double-blind, placebo-controlled study evaluating quality of life and depression symptoms; 54 mg/day genistein with calcium and vitamin D vs placebo.

Osteopenic postmenopausal women enrolled in the multi-center genistein bone study.

Over two years, women with osteopenia taking genistein reported better quality-of-life scores and fewer depression symptoms than those on placebo. Both were self-reported questionnaires collected in a trial designed around bone density, and none of these women were being treated for clinical depression.

Side effects and drug interactions

Common Potential side effects

Mild gastrointestinal complaints such as bloating, gas, or constipation can occur.
Breast tenderness has been reported infrequently with phytoestrogen use.
Rare allergic reactions in soy-sensitive individuals are possible.
Genistein is hormonally active. Women with a history of breast, uterine or ovarian cancer, and anyone taking tamoxifen, an aromatase inhibitor or hormone therapy, should speak to their doctor before using concentrated genistein. The 54 mg daily dose used in the trials is far above what a normal diet supplies.

Important Drug interactions

May interact with tamoxifen and aromatase inhibitors via estrogen receptor activity.
Theoretical interaction with thyroid hormone replacement; separate dosing recommended.
May affect anticoagulant response; monitor INR with warfarin co-use.
Could compound effects of hormone replacement therapy or oral contraceptives.

Frequently asked questions about Genistein

What is genistein used for?

Genistein is a soy isoflavone (a phytoestrogen) that has been studied almost entirely in postmenopausal women, for hot flushes, bone density and blood markers linked to cardiovascular risk. It acts on estrogen receptors, so it is hormonally active in the body. There is no comparable research in men or in premenopausal women.

What is genistein good for?

The best evidence is for bone density and hot flushes in postmenopausal women, from a set of trials run by one Italian research group. Those studies also measured blood markers linked to cardiovascular risk, which is not the same as showing genistein protects the heart. Effects depend on dose, and genistein is often sold inside a soy isoflavone blend.

How much genistein should I take?

The trials on this page all used 54 mg per day of genistein aglycone, taken alongside calcium and vitamin D, for 12 to 24 months. That is considerably more than soy foods normally provide. Follow the product label, and speak to your doctor before taking a concentrated isoflavone dose.

Is genistein safe for hormone-sensitive conditions?

Because it is a phytoestrogen, women with a history of hormone-sensitive cancers should discuss concentrated genistein or isoflavone supplements with their doctor first. Moderate dietary soy is generally considered safe for most people.

What is Genistein?

Genistein is the main isoflavone in soybeans and a well studied phytoestrogen. It binds estrogen receptors, with a preference for the beta subtype, which means it is hormonally active in the body.

What is the recommended dosage of Genistein?

The clinically studied dose is The trials behind this page used 54 mg per day of genistein aglycone for 12 to 24 months, with every participant also taking calcium and vitamin D. Always follow the product label and check with a healthcare provider for personal advice.

Is Genistein safe, and does it have side effects?

For most healthy adults, Genistein is well tolerated at studied doses. Reported effects can include: Mild gastrointestinal complaints such as bloating, gas, or constipation can occur. Breast tenderness has been reported infrequently with phytoestrogen use. It may also interact with some medications. Genistein is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Genistein interact with any medications?

Possible interactions include: May interact with tamoxifen and aromatase inhibitors via estrogen receptor activity. Theoretical interaction with thyroid hormone replacement; separate dosing recommended. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Genistein?

NutraSmarts rates the evidence for Genistein as Moderate (3 out of 5). It is backed by 3 clinical trials and 5 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(5 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, Gaudio A, Mazzaferro S, Frisina A, Frisina N, Lubrano C, Bonaiuto M, D'Anna R, Cannata ML, Corrado F, Adamo EB, Wilson S, Squadrito F. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Annals of Internal Medicine. 2007;Ann Intern Med. 2007 Jun 19;146(12):839-47..PubMedUsed to support: 24-month RCT in 389 osteopenic postmenopausal women showing genistein 54 mg/day increased BMD vs placebo.
  2. Crisafulli A, Marini H, Bitto A, Altavilla D, Squadrito G, Romeo A, Adamo EB, Marini R, D'Anna R, Corrado F, Bartolone S, Frisina N, Squadrito F. Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study. Menopause. 2004;Menopause. 2004 Jul-Aug;11(4):400-4..PubMedUsed to support: 12-month RCT showing genistein 54 mg/day reduced hot flush frequency vs placebo in early postmenopausal women.
  3. Atteritano M, Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Mazzaferro S, D'Anna R, Cannata ML, Gaudio A, Frisina A, Frisina N, Corrado F, Cancellieri F, Lubrano C, Bonaiuto M, Adamo EB, Squadrito F. Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study. The Journal of Clinical Endocrinology and Metabolism. 2007;J Clin Endocrinol Metab. 2007 Aug;92(8):3068-75..PubMedUsed to support: Two-year RCT showing genistein 54 mg/day improved select cardiovascular risk markers in osteopenic postmenopausal women.
  4. D'Anna R, Cannata ML, Atteritano M, Cancellieri F, Corrado F, Baviera G, Triolo O, Antico F, Magno C, Salpietro DC, Granese D, Marini H, Squadrito F. Genistein effects on quality of life and depression symptoms in osteopenic postmenopausal women: a 2-year randomized, double-blind, controlled study. Osteoporosis International. 2014;Osteoporos Int. 2014 Apr;25(4):1255-62..PubMedUsed to support: Two-year RCT showing genistein 54 mg/day improved quality of life and reduced depression symptoms in osteopenic postmenopausal women.
  5. Messina MJ. Emerging evidence on the role of soy in reducing prostate cancer risk. Nutrition Reviews. 2003;Nutr Rev. 2003 Apr;61(4):117-31..PubMedUsed to support: Review of soy foods and prostate cancer risk in men. It is off topic for this page, which covers menopause, bone and women's health, and it does not support any claim made here.