Benefits
Hot flash reduction
Pooled analyses report about 1.7 to 2 fewer hot flashes per day versus placebo in women during and after menopause, but one was significant and another was not (p=0.067). A 12 week trial of two extracts in 252 women found no clinically important effect. Benefit looked clearest with at least 5 flashes a day and 80 mg/day or more for 12 weeks.
Bone density support in menopause
One 12-month randomized trial in 205 women aged 49 to 65 found that lumbar spine bone loss was smaller with a red clover isoflavone supplement (43.5 mg/day) than with placebo (p=0.03), and bone formation markers rose in postmenopausal women. There was no effect at the hip, and the finding has not been repeated.
Total cholesterol
A pooled analysis of 10 trials in 910 women during and after menopause found total cholesterol fell about 0.29 mmol/L with red clover isoflavones (p=0.01). LDL, HDL and triglycerides did not change significantly, and results varied greatly between trials. Effects on heart events have not been studied.
Vaginal dryness
A pooled analysis of red clover trials reported significant improvement in vaginal dryness, and in vaginal maturation value (an objective tissue measure), at the 80 mg/day dose. This outcome still needs confirming in more trials.
Self-rated hair, skin, mood and sleep
In a 90-day crossover trial in 109 postmenopausal women taking 80 mg/day, women rated their scalp hair, skin, libido, mood, sleep and tiredness as better than on placebo. These were self-ratings on a visual scale, not objective measures; nail and body hair did not change.
Mechanism of action
Isoflavone profile
Red clover is rich in biochanin A and formononetin, which gut bacteria and the liver convert to genistein and daidzein. Soy, by contrast, supplies mostly genistein and daidzein directly.
Weak estrogen receptor binding
Isoflavones bind estrogen receptors weakly, with a preference for estrogen receptor beta. This is the proposed basis for effects on hot flashes and bone. In one trial, a year of use did not change estradiol, FSH or LH in postmenopausal women.
Gut bacteria and equol
Some people's gut bacteria convert daidzein to equol, a stronger estrogen receptor binder. Differences in this conversion may explain part of the variation in trial results.
Clinical trials
Systematic review and meta-analysis of 8 randomized placebo-controlled trials (10 comparisons) of red clover isoflavone extract (Kanadys et al. 2021, Nutrients).
Women during and after menopause in 8 trials.
Red clover reduced hot flashes by a weighted mean of 1.73 per day versus placebo (95% CI -3.28 to -0.18, p=0.029). The difference was clearer in postmenopausal women with at least 5 flashes a day, with 12 weeks of use, with 80 mg/day or more and with formulas higher in biochanin A. The authors call for more well-designed trials.
Systematic review and meta-analysis of red clover trials in women during and after menopause (Ghazanfarpour et al. 2016, J Obstet Gynaecol).
Women during and after menopause in the pooled red clover trials.
Hot flash frequency was lower with red clover but not significantly (MD -1.99 per day, 95% CI -4.12 to 0.14, p=0.067), with very high heterogeneity (I2 94.9%). Vaginal dryness improved at 80 mg/day. Effects were smaller for mood, sexual problems and sleep. Women with at least 5 hot flashes a day may benefit more.
Double-blind, randomized, placebo-controlled trial of a red clover isoflavone supplement (43.5 mg/day) for 12 months; same trial as the breast density report, which states the maker Novogen supplied the tablets (Atkinson et al. 2004, Am J Clin Nutr).
205 women aged 49 to 65 (177 completed).
Loss of lumbar spine bone mineral content and density was smaller than with placebo (p=0.04 and p=0.03). No effect at the hip or on bone resorption markers; bone formation markers rose in postmenopausal women. A single trial; same cohort as the breast density study.
Randomized, double-blind, placebo-controlled crossover trial of red clover extract providing 80 mg isoflavones per day (two capsules of 40 mg) for 90 days per phase (Lipovac et al. 2011, Obstet Gynecol Int).
109 postmenopausal women.
Women rated scalp hair, skin, libido, mood, sleep and tiredness as better after red clover than placebo on a visual analogue scale. Nail, body hair, urinary and mucosal ratings did not differ. All outcomes were self-reported.
Double-blind, randomized, placebo-controlled trial of a red clover isoflavone supplement (43.5 mg/day) for 12 months. Funded by the UK Food Standards Agency and Medical Research Council; the maker Novogen supplied the tablets, and one author received Novogen research support (Atkinson et al. 2004, Breast Cancer Res).
205 women aged 49 to 65 with dense mammographic patterns (177 completed).
Breast density fell in both groups with no significant difference between red clover and placebo. Estradiol, FSH and LH, measured only in postmenopausal women, did not differ from placebo. Response depended on estrogen receptor (ESR1) genotype (interaction P=0.009): in women with the TT genotype, density changed +1.4% on red clover versus -9.6% on placebo. Hot flashes and other menopausal symptoms, mild at baseline, did not differ.
Systematic review and meta-analysis of 10 randomized trials (12 comparisons) of red clover isoflavones on blood lipids (Kanadys et al. 2020, Maturitas).
910 women during and after menopause.
Total cholesterol fell 0.29 mmol/L (p=0.0136). LDL (p=0.24), triglycerides (p=0.06) and HDL (p=0.21) did not change significantly. Heterogeneity was very high (I2 88 to 98%).
Randomized, double-blind, placebo-controlled 12 week trial of Promensil (82 mg/day total isoflavones) and Rimostil (57 mg/day), both from red clover, after a 2 week placebo run-in (Tice et al. 2003, JAMA).
252 women aged 45 to 60, recently postmenopausal, with at least 35 hot flashes per week.
Daily hot flash counts fell by 5.1 on Promensil, 5.4 on Rimostil and 5.0 on placebo at 12 weeks, a similar drop in all groups. Promensil reduced hot flashes faster than placebo (P=.03); Rimostil did not. Quality of life and adverse events were similar, and the authors found no clinically important effect.