Red clover: Background. Actions

Common Name

Red clover

Other Names

Cow clover, meadow clover, purple clover, trifoil

Botanical Name / Family

Trifolium pratense L. (family Fabaceae)

Plant Parts Used

Flower head or leaf

Historical Note

Red clover has been used for a long time as an animal fodder as well as a human medicine. Traditionally, it is considered an alternative remedy with good cleansing properties useful in the treatment of skin diseases such as psoriasis, eczema and rashes. A strong infusion was used to ease whooping cough and other spasmodic coughs due to measles, bronchitis and laryngitis. It was recommended for ‘ulcers of every kind, and deep, ragged-edged, and otherwise badly-conditioned burns. It possesses a peculiar soothing property, proves an efficient detergent, and promotes a healthful granulation’. Combined with other herbs, red clover was recommended for syphilis, scrofula, chronic rheumatism, glandular and various skin affections. Interestingly, red clover was not traditionally used for the treatment of menopausal symptoms.

Chemical Components


Flavonoids, including formononetin; flavonols, including isorhamnetin and quercetin glucosides; phenolic acids, including salicylic and p-coumaric acids; volatile oils and other constituents, including sitosterol, starch, fatty acids (BHMA 1983).


Isoflavones, including biochanin A, daidzein, formononetin and genistein; caffeic acid derivatives; and coumestrol (trace).

In the plant, the isoflavones are attached to a sugar molecule, usually glucose. The chemical term for any compound attached to a sugar is ‘glycoside’. The free isoflavone form is known as an ‘aglycone’. The active aglycone is liberated in the gut. Isoflavones are readily absorbed from the gut; they circulate freely in the blood and are excreted in the urine; 50% of ingested isoflavones are eliminated within 12 hours.

The glycoside and aglycone forms of the four main oestrogenic isoflavones are as follows:

Glycoside Aglycone
Ononin Formononetin
Daidzin Daidzein
Sissotrin Biochanin
Genistin Genistein

Clinical note — Phyto-oestrogens and isoflavones

Phyto-oestrogens are plant-based compounds that are structurally similar to oestradiol. The term phyto-oestrogen encompasses isoflavone compounds, such as genistein and daidzein, found predominantly in soya and red clover, and the lignans, such as matairesinol and secoisolariciresinol, found in many fruits, cereals and in linseed. Phyto-oestrogens have been investigated for their potential to reduce the risk of hormone-dependent diseases such as breast and prostate cancers and osteoporosis. The metabolism of isoflavones and lignans is complex and involves gut microbial processes. Isoflavones are present predominantly as glucosides; however, their bioavailability requires initial hydrolysis of the sugar moiety by intestinal [beta]-glucosidases. After absorption, phyto-oestrogens are reconjugated predominantly to glucuronic acid and to a lesser degree to sulfuric acid. There is further metabolism of isoflavones (to equol and O-desmethyl-angolensin) and lignans (to enterodiol and enterolactone) by gut bacteria. In humans, even those on controlled diets, there is large interindividual variation in the metabolism of isoflavones and lignans, particularly in the production of the gut bacterial metabolite equol (from daidzein). Dietary factors and gut microflora directly influence the absorption and metabolism of phyto-oestrogens and is likely to influence the clinical benefits of supplementation with phyto-oestrogens.

Red clover: Main Actions


The pharmacological investigation of red clover has mainly centred around the activity of the isoflavone constituents, especially their oestrogenic activity. The isoflavones biochanin A, genistein and daidzein have varying levels of subtle oestrogenic activity, biochanin A having the strongest effect. Formononetin, however, has very little or no oestrogenic activity. Red clover isoflavones have been shown to have an affinity for oestrogen alpha- and beta-receptors and may act as both agonists and antagonists, depending on the level of endogenous oestrogens. Red clover extract, standardised to contain 15% isoflavones, produced a dose-dependent increase in uterine weight and differentiated vaginal cells, but did not stimulate cell proliferation in mammary glands in an ovariectomised rat model. The extract did not produce any anti-oestrogenic or additive oestrogenic effects when combined with 17-beta-oestradiol. These data suggest that red clover extract is weakly oestrogenic in the ovariectomised rat model.


Phyto-oestrogens and isoflavones may reduce the risk of cancer, including breast cancer. Biochanin A isolated from red clover has been shown to be antimutagenic, as well as protective against chemically-induced DNA damage in vitro. Genistein has been shown to inhibit cell proliferation and in vitro angiogenesis.

An animal study has found that red clover isoflavones significantly increase oestrogen beta-receptor and E-cadherin expression, but decrease transforming growth factor beta-1. These proteins are markers of oestrogen-induced proliferation, preservation of cell phenotype and reduction of the potential for neoplastic and metastatic transformation. These results suggest that red clover isoflavones may be useful in the treatment of prostatic hyperplasia and reduce the risk of neoplastic transformation. A recent study has reported that red clover-derived isoflavones significantly reduced non-malignant prostatic growth in mice by acting as anti-androgenic agents rather than weak oestrogenic substances.