Red clover (Triofolium pratense) is a perennial plant in the legume family (Fabaceae). It grows in many regions of the world, including North America, Europe, Asia, and Africa.^[7] The aerial (above-ground) parts of the red clover plant have been used as a traditional herbal medicine for a variety of ailments,^[8] but the research on red clover has generally centered around menopause.

Red clover contains bioactive plant compounds called isoflavones which possess phytoestrogenic properties. While 16 different isoflavones have been identified in red clover, biochanin A and formononetin are thought to be the most abundant.^[9] Interestingly, upon consumption, biochanin A and formononetin are metabolized into genistein and daidzein (the same isoflavones found in soy), respectively, which are the dominant isoflavones found in the blood during red clover supplementation.^[1][10]

Red clover may be a beneficial supplement in menopause when used to reduce hot flashes. A 2021 meta-analysis of randomized controlled trials found that red clover supplementation taken for 3 months resulted in an average of 1.7 fewer hot flashes daily compared to placebo, particularly in postmenopausal women experiencing at least 5 hot flashes daily.^[1] However, these effects were not sustained in trials performing a 12-month follow-up, and over half of the trials were at least partially funded by the red clover manufacturer, which could bias these results. Red clover might slightly reduce total cholesterol and raise high-density lipoprotein (HDL) in postmenopausal women with no other health conditions, but the effects are so small they likely would not influence overall cardiovascular health.^[11] Research looking at other menopause-related outcomes like vaginal health, sleep behavior, mood, and bone health have had mixed results and are currently inconclusive.^[12]

Preclinical research suggests that red clover may possess antioxidant, antimicrobial, and hypoglycemic (blood-sugar-reducing) properties,^[13][14][15] but establishing the clinical relevance of these effects will require further research.

Red clover supplementation seems to be quite safe when used for up to 3 years.^[16][17] Most trials have not found significant side effects compared to placebo,^[18][13] although larger clinical trials are needed to properly evaluate side effect risk.

The concentration and type of active compounds in red clover can vary depending on how the plant was grown and processed, which can impact its effects on the body.^[3][5] This can result in inconsistent effects when using different extracts of red clover. Variability in effect may also be seen between people due to differences in genetics and the gut microbiome, both of which can impact how isoflavones are metabolized in the body.^[19]

The estrogen-like effects of red clover are due to its contents of isoflavones (biochanin A, formononetin, genistein, and daidzein), which are all considered phytoestrogens. Because of their structural similarity to estrogen, these isoflavones can bind to estrogen receptors in the body which may help reduce some of the symptoms of menopause that occur due to estrogen deficiency. There are two subtypes of estrogen receptors, estrogen receptor beta (ERβ) and estrogen receptor alpha (ERα), which are distributed differently throughout body tissues and have different actions. While estrogen binds both receptors equally, red clover isoflavones have a particular affinity for estrogen receptor β (ERβ) and only a weak affinity for estrogen receptor α (ERα), which means that the estrogenic effects of isoflavones will differ slightly from estrogen.^[20][21]

Red clover also contains many other bioactive compounds, including the polyphenols coumaric acid, ferulic acid, and quercetin. While these contribute to the antioxidant and antimicrobial effects of red clover in vitro, it’s unclear what effects they might have when red clover is used as a supplement.^[15]