Benefits
Hot flash reduction
Pooled analyses report about 1.7 to 2 fewer hot flushes per day versus placebo in women during and after menopause. The results are inconsistent: one pooled analysis was significant, another on the same outcome was not (p=0.067), and trials varied widely. Benefit looked clearest with at least 5 flushes 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 an objective measure of vaginal tissue maturation, at the 80 mg/day dose. Only one of the cited reviews reported this outcome, so it still needs confirming.
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 flushes 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 flushes 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 flushes 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 11 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 (Atkinson et al. 2004, Am J Clin Nutr).
205 women aged 49 to 65 (177 completed).
Lumbar spine bone mineral content and density loss 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 below.
Double-blind, placebo-controlled crossover trial of 80 mg red clover extract 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 for 12 months (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. There was no effect on estradiol, FSH or LH, and no effect on hot flushes or other menopausal symptoms, which were mild at baseline. A reassuring safety result, not a benefit.
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%).