Home Ingredients Formononetin (Red Clover Isoflavone)

Formononetin (Red Clover Isoflavone)

Evidence Level
Preliminary
7 Clinical Trials
6 Documented Benefits
1/5 Evidence Score

Formononetin is an isoflavone, a plant compound with weak estrogen-like activity, found in red clover, in astragalus root and in other legumes. It is the methylated form of daidzein, and in people it is rapidly demethylated to daidzein, which human liver enzymes can also do in the lab, so much of its activity in the body is likely carried by daidzein and its metabolites. Pure formononetin has not been tested in published human trials. The human data come from red clover isoflavone mixtures enriched in formononetin: in one, an improvement in arterial stiffness over 6 weeks seemed confined to the formononetin-enriched mixture but was not statistically significant, another lowered LDL cholesterol over 2 years without helping bone density, and others showed no clear benefit for hot flashes, mood or thinking. Most other findings come from cell and animal studies.

Studied Dose Only red clover mixtures have been tested, with doses given as total isoflavones: Rimostil (formononetin-enriched, now discontinued) at 50 mg/day for 2 years, 28.5 to 85.5 mg/day for 6 months or 57 mg/day for 12 weeks; another enriched mixture at 40 or 80 mg/day for 6 weeks (one trial, two reports).
Active Compound Formononetin (7-hydroxy-4'-methoxyisoflavone), the 4'-O-methyl form of daidzein; in supplements it is usually part of a red clover isoflavone extract, and its glycoside form ononin also occurs in plants.

Benefits

Converted to daidzein in the body

In human pharmacokinetic work, formononetin from a supplement was rapidly and efficiently demethylated, raising blood daidzein to levels like those seen after soy foods. Human liver enzymes perform this step in the lab, and further reduced metabolites appear in urine. Much of its effect in the body may therefore come from daidzein rather than formononetin itself.

Supported by Trial 1, Trial 4

Arterial stiffness with a formononetin-enriched isoflavone mixture

In a placebo-controlled crossover trial in 80 healthy adults aged 45 to 75, red clover isoflavones improved arterial compliance and pulse wave velocity over 6 weeks. The improvement seemed confined to the formononetin-enriched mixture (adjusted p=0.06, not statistically significant), which also lowered an adhesion molecule (VCAM-1). Blood pressure and flow-mediated dilation did not change.

Supported by Trial 1

LDL cholesterol and triglycerides with formononetin-rich red clover extracts

In a 2-year placebo-controlled trial in postmenopausal women, a formononetin-enriched red clover extract (50 mg/day) lowered LDL cholesterol by 12% versus 2% on placebo. In a 6-week trial the formononetin-enriched mixture did not lower LDL, and in a 12-week trial the same extract cut triglycerides by about 14 mg/dl versus placebo, a small effect, without changing LDL.

Supported by Trial 2, Trial 1

Bone density in women taking a formononetin-rich red clover extract

In a 6-month study without a concurrent control group, 46 postmenopausal women taking a formononetin-rich red clover extract had a 3.0 to 4.1% rise in forearm bone density at 57 and 85.5 mg/day. A later 2-year placebo-controlled trial of 50 mg/day found no benefit at the spine, hip or forearm, and bone turnover markers did not change over 12 weeks in another trial.

Supported by Trial 4, Trial 3

Hot flashes, mood and thinking in women around menopause

Formononetin-rich extracts have not shown clear benefit here. In a 12-week trial in 252 women, hot flashes fell by a similar amount on a formononetin-enriched extract and on placebo. In an 8-week trial in women with perimenopausal depression it did no better than placebo, and a 6-month trial in 30 women over 60 found no major effect on cognitive tests.

Supported by Trial 5, Trial 6

Bone, inflammation and oxidative stress in lab and animal studies

In young female rats, oral formononetin (10 mg/kg/day for 30 days) raised bone mineral density without estrogen-like effects on the uterus. A review of cell and animal studies describes antioxidant and anti-inflammatory activity across many models. These results have not been tested with pure formononetin in people.

Supported by Trial 3, Trial 4

Mechanism of action

1

A methylated precursor of daidzein

Formononetin carries a methyl group on the 4' position of daidzein. In human liver microsome tests, the enzymes CYP1A2, 2C9, 2A6, 2D6 and 2C19 removed it to make daidzein, and hydroxylated formononetin derivatives also formed. After red clover supplements, reduced metabolites such as dihydroformononetin and angolensin appear in women's urine.

2

Absorption and circulating forms

In rats, about 22% of an oral dose of formononetin reached the blood, compared with about 7% for its glycoside form ononin (about 22% when ononin converted to formononetin was counted), and in cell models it crossed the gut lining mainly by passive diffusion. In women taking red clover, the isoflavones in serum were mainly conjugated metabolites rather than the free compounds.

3

Weak estrogen-like and anti-inflammatory activity

Formononetin is classed as a phytoestrogen, mainly through its conversion to daidzein. In young rats it did not act like estrogen on the uterus. Cell and animal studies also report antioxidant and anti-inflammatory signaling effects; whether these occur at supplement doses in people is unknown.

Clinical trials

1
Formononetin-Enriched vs Biochanin-Enriched Red Clover Isoflavones: Arterial Stiffness
PubMed

Randomized, double-blind, placebo-controlled crossover trial of red clover isoflavones enriched in formononetin or biochanin A (80 mg/day) in two 6-week periods. (Teede et al. 2003, Arterioscler Thromb Vasc Biol)

80 healthy adults aged 45 to 75 (46 men, 34 postmenopausal women).

Isoflavones as a group improved systemic arterial compliance (p=0.04) and central pulse wave velocity (p=0.02) and lowered total peripheral resistance (p=0.03) versus placebo. The improvement seemed limited to the formononetin-enriched mixture (adjusted p=0.06, not significant), which also reduced circulating VCAM-1 (p<0.01). 24-hour blood pressure and flow-mediated dilation did not change. A mixture, not pure formononetin.

2
Same Trial, Lipids: The Formononetin-Enriched Mixture Did Not Lower LDL
PubMed

Randomized, double-blind, placebo-controlled trial with two parallel groups, each crossing over between an enriched red clover isoflavone mixture (40 mg/day) and placebo for 6 weeks; the maker, Novogen, supplied tablets and partial funding. (Nestel et al. 2004, Eur J Clin Nutr)

46 middle-aged men and 34 postmenopausal women, the same volunteers as the arterial stiffness report, which states the dose as 80 mg/day.

Only the biochanin-enriched mixture lowered LDL cholesterol, and only in men (9.5% versus placebo). The formononetin-enriched mixture did not lower LDL cholesterol, women did not respond significantly, and no other blood lipid changed.

3
Formononetin-Enriched Red Clover Extract for 2 Years: LDL Cholesterol and Bone Density
PubMed

Double-blind, randomized, placebo-controlled trial of Rimostil 50 mg/day with measurements every 6 months for 2 years; the maker, Novogen, supplied the tablets and paid for the biochemical testing and part of the study coordinator's salary. (Clifton-Bligh et al. 2015, Eur J Clin Nutr)

Women at least 1 year past menopause; the abstract does not state the number enrolled.

Serum LDL cholesterol fell 12% on the extract and 2% on placebo (P=0.005). There was no beneficial effect on bone density at the spine, femoral neck or forearm, the trial's other main outcome. A red clover extract, not pure formononetin.

4
Three Doses of a Formononetin-Rich Red Clover Extract for 6 Months (no concurrent control)
PubMed

Double-blind comparison of three doses of Rimostil (28.5, 57 or 85.5 mg/day isoflavones) after a single-blind placebo phase, followed by a washout. (Clifton-Bligh et al. 2001, Menopause)

46 postmenopausal women.

HDL cholesterol rose 15.7 to 28.6% and apolipoprotein B fell 11.5 to 17.0%, with no dose response. Forearm (radius and ulna) bone density rose 4.1% at 57 mg/day and 3.0% at 85.5 mg/day, but not significantly at 28.5 mg/day. Endometrial thickness did not rise. The authors urge caution because there was no concurrent control group. Rimostil is a red clover mixture of genistein, daidzein, formononetin and biochanin, not pure formononetin.

5
Formononetin-Rich Red Clover Tablets and Cognitive Function: 6-Month RCT
PubMed

Randomized, placebo-controlled trial of two tablets of a red clover aglycone isoflavone extract, each tablet holding 25 mg formononetin, 2.5 mg biochanin and under 1 mg each of daidzein and genistein, for 6 months. (Howes et al. 2004, Climacteric)

30 postmenopausal women over 60.

Block design scores rose 12% on isoflavones versus a 3% fall on placebo (p=0.03), but verbal memory improved more on placebo (29% vs 1%, p=0.023) and digit recall fell on isoflavones (p=0.029). None of these differences stayed significant after correction for multiple comparisons, and the authors found no major short-term effect on cognition.

6
ICE Trial: Rimostil and Hot Flashes over 12 Weeks
PubMed

Randomized, double-blind, placebo-controlled 12-week trial of two red clover supplements, Promensil (82 mg/day isoflavones) and Rimostil (57 mg/day). (Tice et al. 2003, JAMA)

252 menopausal women aged 45 to 60 with at least 35 hot flashes per week.

Daily hot flash counts fell by 5.4 on Rimostil, 5.1 on Promensil and 5.0 on placebo. Rimostil did not reduce hot flashes faster than placebo (P=.74). Quality of life and adverse events were similar across groups, and the authors concluded that neither supplement had a clinically important effect. Both products are red clover mixtures, not pure formononetin.

7
Rimostil vs Estradiol, Raloxifene and Placebo in Perimenopausal Depression
PubMed

Randomized, double-blind, placebo-controlled 8-week parallel trial with four arms: transdermal estradiol, raloxifene, Rimostil, a red clover isoflavone product supplied by its maker Novogen (1,000 mg twice daily of the product); funded by the NIMH intramural program and placebo. (Schmidt et al. 2021, Menopause)

Women with perimenopause-related depression (66 randomized, 62 analyzed).

None of the active treatments beat placebo. On the clinician-rated depression scale, week-8 scores were 11.2 on Rimostil and 7.8 on placebo, numerically worse on the extract, and self-rated scales showed no group differences. Cognition did not improve with any treatment. A red clover mixture, not pure formononetin; the paper does not give its isoflavone content per dose.

Side effects and drug interactions

Common Potential side effects

Safety data for isolated formononetin in people are lacking; safety information comes from red clover isoflavone extracts.
In a 12-week trial of a formononetin-enriched red clover extract (57 mg/day), adverse events were similar to placebo. In a 6-month study at 28.5 to 85.5 mg/day, endometrial thickness did not rise significantly.
Pregnancy and breastfeeding: avoid concentrated isoflavone supplements, because of their estrogen-like activity.
Hormone-sensitive conditions, including a history of breast or uterine cancer: talk to your doctor before use.
Label accuracy varies: an analysis of 33 phytoestrogen supplements found considerable differences between measured and claimed isoflavone content.
Allergy to red clover or other legumes is possible.

Important Drug interactions

Tamoxifen and aromatase inhibitors: formononetin is converted to the phytoestrogen daidzein; do not combine without your oncologist's advice.
Hormone therapy and birth control pills: estrogen-like effects may add to or interfere with them; ask your doctor.
Drugs processed by liver CYP enzymes: several CYP enzymes metabolize formononetin in lab tests, but a red clover supplement (120 mg isoflavones per day for 2 weeks) did not change blood levels of probe drugs for CYP1A2, CYP2C9, CYP2D6 and CYP3A4/5 in 15 women. Other drugs and pure formononetin have not been tested; ask your pharmacist about narrow-margin drugs.

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Frequently asked questions about Formononetin (Red Clover Isoflavone)

What is formononetin?

Formononetin is an isoflavone, a plant compound with weak estrogen-like activity. It is found in red clover, astragalus root and other legumes. In the body it is converted to daidzein, one of the main soy isoflavones.

How is formononetin different from red clover and biochanin A?

Red clover is the whole herb, and its extracts contain several isoflavones, mainly formononetin and biochanin A. Biochanin A becomes genistein in the body, while formononetin becomes daidzein. Some red clover extracts are enriched in formononetin, but they still contain the other isoflavones, so their effects reflect the whole mixture.

Has formononetin been tested on its own in people?

Not in published trials. Human studies used red clover extracts enriched in formononetin: in one, an arterial stiffness improvement over 6 weeks seemed confined to the formononetin-enriched mixture but was not statistically significant, and another lowered LDL cholesterol over 2 years, while trials on hot flashes, mood, thinking and bone density found no clear benefit. Effects of the pure compound come from cell and animal studies.

How much formononetin is used?

No dose of pure formononetin has been established. Formononetin-enriched red clover extracts were studied at about 28.5 to 85.5 mg/day of total isoflavones, most often 50 to 57 mg/day. Follow the product label and check how much formononetin it actually lists.

Who should talk to a doctor before taking formononetin?

Because it becomes the phytoestrogen daidzein, anyone who is pregnant or breastfeeding, has a history of hormone-sensitive cancer, or takes tamoxifen, an aromatase inhibitor or hormone therapy should talk to their doctor first. Long-term safety data are limited.

What is Formononetin used for?

Formononetin has several researched uses. In human pharmacokinetic work, formononetin from a supplement was rapidly and efficiently demethylated, raising blood daidzein to levels like those seen after soy foods.

What is the recommended dosage of Formononetin?

The clinically studied dose is Only red clover mixtures have been tested, with doses given as total isoflavones: Rimostil (formononetin-enriched, now discontinued) at 50 mg/day for 2 years, 28.5 to 85. Always follow the product label and check with a healthcare provider for personal advice.

Is Formononetin safe, and does it have side effects?

Side effects and cautions reported for Formononetin include: Safety data for isolated formononetin in people are lacking; safety information comes from red clover isoflavone extracts. In a 12-week trial of a formononetin-enriched red clover extract (57 mg/day), adverse events were similar to placebo. In a 6-month study at 28.5 to 85. It may also interact with some medications. Formononetin 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 Formononetin interact with any medications?

Possible interactions include: Tamoxifen and aromatase inhibitors: formononetin is converted to the phytoestrogen daidzein; do not combine without your oncologist's advice. Hormone therapy and birth control pills: estrogen-like effects may add to or interfere with them; ask your doctor. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Formononetin?

NutraSmarts rates the evidence for Formononetin as Preliminary (1 out of 5). It is backed by 7 clinical trials and 16 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(16 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. Teede HJ, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJ. Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women. Arterioscler Thromb Vasc Biol. 2003;23(6):1066-71. doi: 10.1161/01.ATV.0000072967.97296.4A.PubMedUsed to support: Randomized, double-blind, placebo-controlled crossover trial in 80 healthy adults aged 45 to 75 (46 men, 34 women) given 80 mg/day of red clover isoflavones enriched in biochanin A or formononetin for 6 weeks. Isoflavones improved arterial compliance (p=0.04) and pulse wave velocity (p=0.02), with improvements seemingly limited to the formononetin-enriched mixture (adjusted p=0.06), which also reduced VCAM-1 (p<0.01). Blood pressure and flow-mediated dilation did not change.
  2. Nestel P, Cehun M, Chronopoulos A, DaSilva L, Teede H, McGrath B. A biochanin-enriched isoflavone from red clover lowers LDL cholesterol in men. Eur J Clin Nutr. 2004;58(3):403-8. doi: 10.1038/sj.ejcn.1601796.PubMedUsed to support: Lipid report from the same 80 volunteers (46 men, 34 postmenopausal women), stating the dose as 40 mg/day for 6 weeks. Only the biochanin-enriched mixture lowered LDL cholesterol, and only in men; the formononetin-enriched mixture did not lower LDL cholesterol, and no other lipid changed. Novogen Ltd provided partial support, including tablets and outside monitoring.
  3. Clifton-Bligh PB, Nery ML, Clifton-Bligh RJ, Visvalingam S, Fulcher GR, Byth K, Baber R. Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized, double-blind, placebo-controlled study. Eur J Clin Nutr. 2015;69(1):134-42. doi: 10.1038/ejcn.2014.207.PubMedUsed to support: Double-blind, randomized, placebo-controlled 2-year trial of the formononetin-enriched red clover extract Rimostil (50 mg/day) in women at least 1 year past menopause. LDL cholesterol fell 12% versus 2% on placebo (P=0.005). There was no beneficial effect on bone density at the spine, femoral neck or forearm. The abstract does not give the number of women. Per the paper's acknowledgments, Novogen Ltd, the maker, supplied the study medication, paid for the biochemical testing and paid part of the study coordinator's salary.
  4. Clifton-Bligh PB, Baber RJ, Fulcher GR, Nery ML, Moreton T. The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause. 2001;8(4):259-65. doi: 10.1097/00042192-200107000-00007.PubMedUsed to support: 46 postmenopausal women took Rimostil (genistein, daidzein, formononetin and biochanin) at 28.5, 57 or 85.5 mg/day for 6 months after a single-blind placebo phase. HDL cholesterol rose and apolipoprotein B fell at all doses, and forearm bone density rose at the two higher doses, with no rise in endometrial thickness. There was no concurrent control group, and the authors advise cautious interpretation.
  5. Howes JB, Bray K, Lorenz L, Smerdely P, Howes LG. The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women. Climacteric. 2004;7(1):70-7. doi: 10.1080/13697130310001651490.PubMedUsed to support: Randomized, placebo-controlled 6-month trial in 30 postmenopausal women over 60 of a red clover extract whose tablets each held 25 mg formononetin and 2.5 mg biochanin. Block design improved and verbal memory and digit recall did worse than placebo, but none of these differences survived correction for multiple comparisons; the authors found no major short-term effect on cognitive function.
  6. Tice JA, Ettinger B, Ensrud K, Wallace R, Blackwell T, Cummings SR. Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial. JAMA. 2003;290(2):207-14. doi: 10.1001/jama.290.2.207.PubMedUsed to support: Randomized, double-blind, placebo-controlled 12-week trial in 252 menopausal women with at least 35 hot flashes a week. Hot flash counts fell by 5.4 a day on Rimostil (57 mg/day), 5.1 on Promensil (82 mg/day) and 5.0 on placebo; Rimostil did not reduce hot flashes faster than placebo (P=.74). The authors concluded neither supplement had a clinically important effect.
  7. Schult TM, Ensrud KE, Blackwell T, Ettinger B, Wallace R, Tice JA. Effect of isoflavones on lipids and bone turnover markers in menopausal women. Maturitas. 2004;48(3):209-18. doi: 10.1016/j.maturitas.2003.09.027.PubMedUsed to support: Lipid and bone marker results from the same 12-week, 252-woman trial. Triglycerides fell 14.4 mg/dl on Rimostil (P=0.02) and 10.9 mg/dl on Promensil (P=0.05) versus placebo, mainly in women with high baseline levels; the authors call the effect small. Total and LDL cholesterol and bone turnover markers did not differ between groups.
  8. Schmidt PJ, Wei SM, Martinez PE, Dor RRB, Guerrieri GM, Palladino PP, Harsh VL, Li HJ, Wakim P, Nieman LK, Rubinow DR. The short-term effects of estradiol, raloxifene, and a phytoestrogen in women with perimenopausal depression. Menopause. 2021;28(4):369-383. doi: 10.1097/GME.0000000000001724.PubMedUsed to support: Randomized, double-blind, placebo-controlled 8-week trial in women with perimenopausal depression (66 randomized) comparing estradiol, raloxifene, Rimostil (1,000 mg twice daily) and placebo. No active treatment beat placebo; clinician-rated depression scores at week 8 were numerically higher (worse) on Rimostil than placebo, and cognition did not improve. Funded by the NIMH Intramural Research Program; Rimostil was supplied by Novogen and is described in the paper as now discontinued.
  9. Setchell KD, Brown NM, Desai P, Zimmer-Nechemias L, Wolfe BE, Brashear WT, Kirschner AS, Cassidy A, Heubi JE. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr. 2001;131(4 Suppl):1362S-75S. doi: 10.1093/jn/131.4.1362S.PubMedUsed to support: Human pharmacokinetic work on isoflavones. Formononetin and biochanin A from one phytoestrogen supplement were rapidly and efficiently demethylated, giving high plasma daidzein and genistein levels like those after soy foods; methoxylated isoflavones behaved differently depending on the position of the methoxyl group. An analysis of 33 supplements found considerable differences between measured and claimed isoflavone content.
  10. Tolleson WH, Doerge DR, Churchwell MI, Marques MM, Roberts DW. Metabolism of biochanin A and formononetin by human liver microsomes in vitro. J Agric Food Chem. 2002;50(17):4783-90. doi: 10.1021/jf025549r.PubMedUsed to support: Laboratory study with human liver microsomes. Formononetin was demethylated to daidzein by CYP1A2, 2C9, 2A6, 2D6 and 2C19, and three hydroxylated formononetin derivatives were identified. The authors conclude liver enzymes, not only gut bacteria, may convert these methylated isoflavones to more potent phytoestrogens.
  11. Heinonen SM, Wähälä K, Adlercreutz H. Identification of urinary metabolites of the red clover isoflavones formononetin and biochanin A in human subjects. J Agric Food Chem. 2004;52(22):6802-9. doi: 10.1021/jf0492767.PubMedUsed to support: Seven women took four red clover supplements, and their urinary metabolites were identified. Dihydroformononetin and angolensin were reported as new reduced metabolites of formononetin, and possible metabolic pathways were proposed.
  12. Chen L, Choi J, Leonard SW, Banuvar S, Barengolts E, Viana M, Chen SN, Pauli GF, Bolton JL, van Breemen RB. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. doi: 10.1021/acs.jafc.0c05856.PubMedUsed to support: 15 peri- and postmenopausal women took a standardized red clover supplement containing formononetin and biochanin A (120 mg isoflavones per day) for 2 weeks. Blood levels of probe drugs for CYP1A2, CYP2C9, CYP2D6 and CYP3A4/5 did not change, and the isoflavones circulated mainly as conjugated metabolites.
  13. Luo LY, Fan MX, Zhao HY, Li MX, Wu X, Gao WY. Pharmacokinetics and Bioavailability of the Isoflavones Formononetin and Ononin and Their in Vitro Absorption in Ussing Chamber and Caco-2 Cell Models. J Agric Food Chem. 2018;66(11):2917-2924. doi: 10.1021/acs.jafc.8b00035.PubMedUsed to support: Rat and cell study. Oral bioavailability was 21.8% for formononetin and 7.3% for its glycoside form ononin (21.7% counting ononin converted to formononetin). Formononetin crossed Caco-2 cells mainly by passive diffusion and was better absorbed in the large intestine than the small intestine. Animal and cell findings only.
  14. Gautam AK, Bhargavan B, Tyagi AM, Srivastava K, Yadav DK, Kumar M, Singh A, Mishra JS, Singh AB, Sanyal S, Maurya R, Manickavasagam L, Singh SP, Wahajuddin W, Jain GK, Chattopadhyay N, Singh D. Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats. J Nutr Biochem. 2011;22(4):318-27. doi: 10.1016/j.jnutbio.2010.02.010.PubMedUsed to support: Rat study. Oral formononetin (10 mg/kg/day for 30 days) in recently weaned female rats increased bone mineral density at several sites but did not change bone formation rate, and showed no estrogen-like effect on the uterus. Its plasma bioavailability was lower than that of the related isoflavone cladrin. Animal findings only.
  15. Ding M, Bao Y, Liang H, Zhang X, Li B, Yang R, Zeng N. Potential mechanisms of formononetin against inflammation and oxidative stress: a review. Front Pharmacol. 2024;15:1368765. doi: 10.3389/fphar.2024.1368765.PubMedUsed to support: Review of cell and animal studies published from 2013 to 2023. Formononetin is abundant in legumes and grasses, including Astragalus mongholicus (astragalus root) and oats, and showed antioxidant and anti-inflammatory activity in many disease models with mild or no toxicity reported. No human trials are described in the abstract.
  16. 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 on nonhormone options for hot flashes. Supplements and herbal remedies are listed as not recommended (Levels I to II), as are soy foods, soy extracts and the soy metabolite equol (Level II). Cited from the published abstract.