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Soy Isoflavones (Glycine max)

Glycine max
Evidence Level
Moderate
5 Clinical Trials
3 Documented Benefits
3/5 Evidence Score

Soy isoflavones, mainly genistein, daidzein and glycitein, are soybean compounds that act weakly like estrogen, so they are called phytoestrogens. Supplements are most often studied for hot flashes after menopause. A meta-analysis of 17 placebo-controlled trials found about 21% fewer hot flashes and 26% lower severity, but a Cochrane review judged the evidence for phytoestrogens inconclusive, a 2-year trial of 200 mg a day found no relief, and the North American Menopause Society does not recommend soy foods or soy extracts for hot flashes. For bone, a 2-year trial of genistein raised spine and hip bone density in women with low bone mass, while two US trials of isoflavone tablets found no protection against bone loss. Isoflavone extracts taken alone did not lower cholesterol. Women with a history of hormone-sensitive cancer or on hormone therapy should ask their doctor first.

Studied Dose Hot flash trials: median 54 mg a day of isoflavones (aglycone equivalents) for 6 weeks to 12 months. Bone trials: 54 mg genistein, 80 to 120 mg or 200 mg of soy isoflavones a day for 2 to 3 years. Cholesterol: about 70 mg a day of extract for 1 to 3 months (no effect).
Active Compound Genistein, daidzein and glycitein from soybean extract; products differ in total isoflavone content and in the genistein share.

Benefits

Hot flash frequency and severity

A meta-analysis of 17 placebo-controlled trials found that soy isoflavones (median 54 mg a day) cut hot flash frequency by about 21% and severity by about 26%, more with genistein-rich products. A review of 43 phytoestrogen trials found no conclusive evidence and a strong placebo effect, a 2-year trial of 200 mg a day found no benefit for symptoms, and the North American Menopause Society does not recommend soy extracts for hot flashes.

Supported by Trial 1

Bone density after menopause

In a 2-year trial in 389 women with low bone mass, 54 mg a day of genistein raised spine and femoral neck bone density while the placebo group lost bone. A meta-analysis of extract trials found about 2.4% higher spine density but no hip effect. Two US trials of 80 to 200 mg a day of isoflavone tablets for 2 to 3 years found no effect on spine or hip bone loss. Fractures were not studied.

Supported by Trial 2, Trial 3

Total and LDL cholesterol

In a meta-analysis of 11 trials of soy protein intake, soy isoflavones given with soy protein lowered total cholesterol by about 1.8% and LDL cholesterol by about 3.6%, with larger LDL drops in people with high cholesterol. A later meta-analysis of isoflavone extracts taken without soy protein (about 70 mg a day for 1 to 3 months) found no significant effect on total or LDL cholesterol in menopausal women with normal cholesterol.

Supported by Trial 5

Mechanism of action

1

Weak estrogen-like activity

In lab binding and cell studies, genistein and daidzein activated both estrogen receptor types far more weakly than the body's own estradiol, and genistein favored estrogen receptor beta over receptor alpha. This is the proposed reason for effects on hot flashes and bone, and the reason women with hormone-sensitive conditions are advised to be cautious.

2

Equol production by gut bacteria

Some people's gut bacteria convert daidzein into equol, which is more biologically potent than the isoflavones in food, and not everyone makes it. A systematic review of 42 soy isoflavone trial reports found better heart risk factors in equol producers in 14 of them, mostly from underpowered secondary analyses; the other 28 mainly reported null results.

3

Bone turnover

In the genistein trial, genistein lowered urine markers of bone breakdown and raised a blood marker of bone formation compared with placebo, without thickening the uterine lining over 2 years.

Clinical trials

1
Soy isoflavones and hot flashes (meta-analysis)
PubMed

Systematic review and meta-analysis of double-blind randomized placebo-controlled trials of extracted or synthesized soy isoflavones (Taku et al. 2012, Menopause)

19 trials in perimenopausal and postmenopausal women; 13 trials pooled for frequency and 9 for severity.

Isoflavones (median 54 mg a day for 6 weeks to 12 months) reduced hot flash frequency by 20.6% and severity by 26.2% compared with placebo. Heterogeneity between trials was high, and products with more than 18.8 mg of genistein worked about twice as well.

2
Genistein and bone density in women with low bone mass
PubMed

Randomized double-blind placebo-controlled trial of 54 mg a day of genistein for 24 months; both groups also took calcium and vitamin D (Marini et al. 2007, Ann Intern Med)

389 osteopenic postmenopausal women at 3 university centers in Italy.

Spine bone density rose 0.049 g/cm2 with genistein and fell 0.053 g/cm2 with placebo (difference 0.10 g/cm2); femoral neck density differed by 0.062 g/cm2. Bone breakdown markers fell. Stomach side effects were more common with genistein (19% vs 8%). Fractures were not measured.

3
SIRBL: soy isoflavones for reducing bone loss
PubMed

3-year randomized double-blind placebo-controlled trial of 80 or 120 mg a day of soy isoflavone tablets, with calcium and vitamin D in all groups; NIH funded, with the isoflavone tablets (Novasoy) donated by their maker, Archer Daniels Midland (Alekel et al. 2010, Am J Clin Nutr)

224 healthy postmenopausal women aged 45.8 to 65.0 without osteoporosis.

No treatment effect on spine, hip, femoral neck or whole-body bone density; bone density fell in all groups. After statistical adjustment, 120 mg a day showed a small protective effect at the femoral neck only.

4
Soy isoflavones for bone loss and menopausal symptoms
PubMed

Randomized double-blind placebo-controlled trial of 200 mg a day of soy isoflavone tablets for 2 years (Levis et al. 2011, Arch Intern Med)

248 women aged 45 to 60 within 5 years of menopause.

No difference from placebo in bone loss at the spine, hip or femoral neck. Hot flashes and constipation were more common in the soy group, and other outcomes did not differ.

5
Soy isoflavone extracts alone and cholesterol (meta-analysis)
PubMed

Meta-analysis of randomized placebo-controlled trials of extracted soy isoflavones taken without soy protein for 1 to 3 months; the pooled results were in menopausal women with normal cholesterol (Taku et al. 2008, Ther Clin Risk Manag)

Pooled data from 10 trials (total cholesterol) and 9 trials (LDL cholesterol).

An average of 70 mg a day of isoflavones (27 to 132 mg) had no significant effect on total cholesterol (+0.01 mmol/L) or LDL cholesterol (+0.03 mmol/L) compared with placebo.

Side effects and drug interactions

Common Potential side effects

Stomach upset: in a 2-year genistein trial, 19% of women taking genistein had gastrointestinal side effects vs 8% on placebo, and more of them stopped the study; constipation was more common with 200 mg a day of isoflavones.
In a 3-year trial of 80 or 120 mg a day, adverse events and uterine lining thickness did not differ from placebo.
A Cochrane review found no sign of estrogen-like stimulation of the uterine lining or vagina with phytoestrogens used for up to 2 years.
Some people are allergic to soy, and possible side effects of soy include bloating, constipation, diarrhea and nausea.
Because isoflavones act weakly like estrogen, women with a history of hormone-sensitive cancer should talk to their doctor before using concentrated supplements.

Important Drug interactions

Tamoxifen and aromatase inhibitors: because isoflavones act weakly like estrogen, people taking these breast cancer drugs should talk with their oncologist before using concentrated soy isoflavones.
Hormone therapy (estrogen): effects could add up; discuss with your doctor.
Levothyroxine: case reports suggest soy products may reduce its absorption, although the only randomized crossover study found soy isoflavones taken together with levothyroxine did not change its absorption; tell your doctor if you start soy supplements.
MAO inhibitor antidepressants: certain soy products high in tyramine have been reported to interact with these drugs and cause dangerously high blood pressure.

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Frequently asked questions about Soy Isoflavones (Glycine max)

How much soy isoflavones should I take?

Hot flash studies used a median of about 54 mg a day, and bone studies used 54 to 200 mg a day. Whole soy foods like tofu, edamame and soy milk also provide isoflavones.

What are soy isoflavones used for?

They are plant compounds that act weakly like estrogen. They are mainly studied for hot flashes after menopause: pooled trials found fewer and milder hot flashes, but other trials did not, and the North American Menopause Society does not recommend them for hot flashes. Bone results differ between trials, and extracts taken alone did not lower cholesterol.

Are soy isoflavones safe for hormone-sensitive conditions?

Because isoflavones act weakly like estrogen, women with a history of hormone-sensitive cancers, such as some breast cancers, should talk with their doctor before using concentrated supplements. Moderate amounts of soy food are a separate question to discuss with your doctor.

What is equol, and why does it matter?

Some people's gut bacteria convert the isoflavone daidzein into equol, which is more biologically potent, and not everyone makes it. This is one proposed reason why responses to soy isoflavones vary from person to person.

What is Soy Isoflavones?

Soy isoflavones, mainly genistein, daidzein and glycitein, are soybean compounds that act weakly like estrogen, so they are called phytoestrogens. Supplements are most often studied for hot flashes after menopause.

What is Soy Isoflavones used for?

Soy Isoflavones is researched primarily for Bone Health and Menopause Support. A meta-analysis of 17 placebo-controlled trials found that soy isoflavones (median 54 mg a day) cut hot flash frequency by about 21% and severity by about 26%, more with genistein-rich products.

Does Soy Isoflavones interact with any medications?

Possible interactions include: Tamoxifen and aromatase inhibitors: because isoflavones act weakly like estrogen, people taking these breast cancer drugs should talk with their oncologist before using concentrated soy isoflavones. Hormone therapy (estrogen): effects could add up; discuss with your doctor. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Soy Isoflavones?

NutraSmarts rates the evidence for Soy Isoflavones as Moderate (3 out of 5). It is backed by 5 study summaries and 13 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(13 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. Lethaby A, Marjoribanks J, Kronenberg F, Roberts H, Eden J, Brown J. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev. 2013;2013(12):CD001395. doi: 10.1002/14651858.CD001395.pub4.PubMedUsed to support: Cochrane review of 43 trials (4,364 women): no conclusive evidence that phytoestrogen supplements reduce hot flashes or night sweats; most trials could not be pooled, many were small with high risk of bias, and placebo groups improved by 1% to 59%. Four trials not pooled suggested extracts with more than 30 mg a day of genistein consistently reduced hot flash frequency. No estrogen-like stimulation of the endometrium or vagina was seen for up to 2 years.
  2. Taku K, Melby MK, Kronenberg F, Kurzer MS, Messina M. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause. 2012;19(7):776-90. doi: 10.1097/gme.0b013e3182410159.PubMedUsed to support: Meta-analysis of 17 double-blind placebo-controlled trials: soy isoflavones (median 54 mg a day aglycone equivalents, 6 weeks to 12 months) reduced hot flash frequency by 20.6% and severity by 26.2% versus placebo, with high heterogeneity; products with more genistein were more potent.
  3. Taku K, Umegaki K, Sato Y, Taki Y, Endoh K, Watanabe S. Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr. 2007;85(4):1148-56. doi: 10.1093/ajcn/85.4.1148.PubMedUsed to support: Meta-analysis of 11 randomized trials of soy protein intake: soy isoflavones given with soy protein lowered total cholesterol by 1.77% and LDL cholesterol by 3.58%, with no change in HDL cholesterol or triglycerides; LDL reductions were larger in people with high cholesterol.
  4. 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. Ann Intern Med. 2007;146(12):839-47. doi: 10.7326/0003-4819-146-12-200706190-00005.PubMedUsed to support: 24-month RCT in 389 osteopenic postmenopausal women: 54 mg a day of genistein increased spine (difference 0.10 g/cm2) and femoral neck (0.062 g/cm2) bone density versus placebo, lowered bone resorption markers and did not change endometrial thickness; gastrointestinal side effects were more common (19% vs 8%); fractures were not measured.
  5. Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, Watanabe S. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2010;19(1):33-42.PubMedUsed to support: Meta-analysis of soy isoflavone extract trials in 1,240 menopausal women: an average 82 mg a day for 6 to 12 months increased spine bone density by 2.38% versus control, with no significant effect at the femoral neck, total hip or trochanter.
  6. Alekel DL, Van Loan MD, Koehler KJ, Hanson LN, Stewart JW, Hanson KB, Kurzer MS, Peterson CT. The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr. 2010;91(1):218-30. doi: 10.3945/ajcn.2009.28306.PubMedUsed to support: SIRBL 3-year RCT in 224 postmenopausal women: 80 or 120 mg a day of soy isoflavones did not spare bone density at the spine, femur, femoral neck or whole body; after adjustment, 120 mg showed a modest effect at the femoral neck only. No effect on adverse events or endometrial thickness. NIH funded; Archer Daniels Midland donated the isoflavone tablets (Novasoy).
  7. Levis S, Strickman-Stein N, Ganjei-Azar P, Xu P, Doerge DR, Krischer J. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial. Arch Intern Med. 2011;171(15):1363-9. doi: 10.1001/archinternmed.2011.330.PubMedUsed to support: 2-year RCT in 248 women within 5 years of menopause: 200 mg a day of soy isoflavones did not prevent bone loss or menopausal symptoms; hot flashes and constipation were more common with soy.
  8. North American Menopause Society. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause. 2023;30(6):573-590. doi: 10.1097/GME.0000000000002200.PubMedUsed to support: Position statement from an expert advisory panel (PubMed lists only a placeholder collective author). It lists soy foods and soy extracts, and the soy metabolite equol, as not recommended for menopausal hot flashes (Level II, limited or inconsistent evidence), along with supplements and herbal remedies in general.
  9. Taku K, Umegaki K, Ishimi Y, Watanabe S. Effects of extracted soy isoflavones alone on blood total and LDL cholesterol: Meta-analysis of randomized controlled trials. Ther Clin Risk Manag. 2008;4(5):1097-103. doi: 10.2147/tcrm.s3262.PubMedUsed to support: Meta-analysis of 10 and 9 placebo-controlled trials: about 70 mg a day (27 to 132 mg) of extracted soy isoflavones taken without soy protein for 1 to 3 months had no significant effect on total or LDL cholesterol in menopausal women with normal cholesterol.
  10. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998;139(10):4252-63. doi: 10.1210/endo.139.10.6216.PubMedUsed to support: Laboratory binding and cell studies: genistein competed more strongly for estrogen receptor beta than alpha, and estradiol was far more potent than genistein or daidzein at activating both receptor types.
  11. Birru RL, Ahuja V, Vishnu A, Evans RW, Miyamoto Y, Miura K, Usui T, Sekikawa A. The impact of equol-producing status in modifying the effect of soya isoflavones on risk factors for CHD: a systematic review of randomised controlled trials. J Nutr Sci. 2016;5:e30. doi: 10.1017/jns.2016.18.PubMedUsed to support: Systematic review: equol, made by gut bacteria from daidzein, is more biologically potent than dietary isoflavones and not everyone produces it. Of 42 trial reports that recorded equol status, 14 found better heart risk factors in equol producers, mostly from underpowered secondary analyses; the other 28 primarily reported null results.
  12. Gatta E, Maltese V, Cavadini M, Anelli V, Bambini F, Buoso C, Facondo P, Pirola I, Delbarba A, Cappelli C. Interference or Noninterference Between Soy and Levothyroxine: That Is the Question. A Narrative Review of Literature. Endocr Pract. 2023;29(11):897-901. doi: 10.1016/j.eprac.2023.08.009.PubMedUsed to support: Narrative review: a few case reports suggest soy products may interfere with levothyroxine tablet absorption, but the only prospective randomized crossover study found no difference in absorption when levothyroxine and soy isoflavones were taken together; any effect seems to have little clinical impact.
  13. National Center for Complementary and Integrative Health. Soy NCCIH, National Institutes of Health. 2025;Web page, last updated April 2025 (not PubMed-indexed)..SourceUsed to support: Not PubMed-indexed: US government fact sheet. It notes that soy isoflavone supplements or soy protein may help reduce hot flashes, though the effect may be small and results have not been consistent; that some people are allergic to soy; that side effects may include bloating, constipation, diarrhea and nausea; that certain soy products high in tyramine have been reported to interact with MAO inhibitors; that concentrated isoflavone extracts have been used safely in studies for up to 6 months, with safety above food amounts uncertain in pregnancy and breastfeeding; and that soy isoflavones may not share soy protein's small cholesterol-lowering effect.