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Soy Isoflavones (Glycine max)

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

Soy isoflavones, mainly genistein, daidzein and glycitein, are plant compounds from soybeans that can weakly act like estrogen in the body, which is why 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 overall evidence for phytoestrogens inconclusive, and a 2-year trial of 200 mg a day found no relief. For bone, a 2-year trial of genistein increased spine and hip bone density in women with low bone mass, while two US trials of soy isoflavone tablets found no protection against bone loss. Soy isoflavones also lower LDL cholesterol slightly. Women with a history of hormone-sensitive cancer, or taking hormone therapy, should talk to their doctor before using concentrated supplements.

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.
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%, with more effect from products richer in genistein. Other studies show mixed results: a 2013 review of 43 trials found no conclusive evidence for phytoestrogens overall and noted a strong placebo effect, and a 2-year trial of 200 mg a day did not relieve symptoms.

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 increased spine and hip 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. Other trials show mixed results: two US trials of 80 to 200 mg a day of soy isoflavone tablets for 2 to 3 years found no protection against bone loss. Fractures were not studied.

Supported by Trial 2, Trial 3

Total and LDL cholesterol

A meta-analysis of 11 randomized trials found that soy isoflavones lowered total cholesterol by about 1.8% and LDL cholesterol by about 3.6%, with larger drops in people with high cholesterol. HDL cholesterol and triglycerides did not change. The effect is small next to diet changes or medication.

Supported by Trial 1, Trial 3

Mechanism of action

1

Weak estrogen-like activity

Genistein and daidzein bind estrogen receptors, much more weakly than the body's own estradiol. 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, a more active compound. Whether a person makes equol is one proposed reason responses to soy isoflavones vary.

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 (Alekel et al. 2010, Am J Clin Nutr)

224 healthy postmenopausal women aged about 46 to 65 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.

Side effects and drug interactions

Common Potential side effects

Generally well tolerated in trials of up to 2 to 3 years.
Stomach upset: in the genistein trial, 19% of women taking genistein had gastrointestinal side effects vs 8% on placebo; constipation was more common with 200 mg a day of isoflavones.
No thickening of the uterine lining was seen in trials of up to 2 years.
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: isoflavones act weakly like estrogen, so people on these breast cancer drugs should not use concentrated soy isoflavones without their oncologist's advice.
Hormone therapy (estrogen): effects could add up; discuss with your doctor.
Levothyroxine: soy products may reduce its absorption; take the medicine at a different time and tell your doctor if you start soy supplements.

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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, with mixed results, and they lower LDL cholesterol slightly. Evidence for bone density is mixed.

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, a more active compound. 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 plant compounds from soybeans that can weakly act like estrogen in the body, which is why 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 Cardiovascular, 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%, with more effect from products richer in genistein.

What is the recommended dosage of Soy Isoflavones?

The clinically studied dose is 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. Always follow the product label and check with a healthcare provider for personal advice.

Is Soy Isoflavones safe, and does it have side effects?

For most healthy adults, Soy Isoflavones is well tolerated at studied doses. Reported effects can include: Generally well tolerated in trials of up to 2 to 3 years. Stomach upset: in the genistein trial, 19% of women taking genistein had gastrointestinal side effects vs 8% on placebo; constipation was more common with 200 mg a day of isoflavones. It may also interact with some medications. Soy Isoflavones 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 Soy Isoflavones interact with any medications?

Possible interactions include: Tamoxifen and aromatase inhibitors: isoflavones act weakly like estrogen, so people on these breast cancer drugs should not use concentrated soy isoflavones without their oncologist's advice. 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 4 clinical trials and 7 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(7 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 flushes 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%. Extracts with more than 30 mg a day of genistein consistently reduced hot flush frequency in four trials. No endometrial stimulation 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: soy isoflavones 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.
  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.