Red Clover (Trifolium pratense)
Red clover is a perennial herb traditionally used to treat skin conditions such as eczema and psoriasis, whooping cough, and respiratory problems. The isoflavones present in red clover have estrogen-like effects and have been the subject of intense research over the last decade.
Data on red clover’s potential for reducing the symptoms of menopause and for decreasing the risk of breast cancer are inconclusive. Overuse of isoflavone supplements can increase the risk of hormone-sensitive cancer.
Recent findings from a preclinical study suggest that red clover may increase resistance of prostate cancer cells to high-dose radiation while inhibiting the growth of normal prostate cells. Until definitive data are available, patients should avoid use of red clover during radiotherapy for prostate cancer.
—Barrie Cassileth, PhD
ALSO KNOWN AS: Cow clover, wild clover, purple clover, beebread, cow grass, meadow clover, purple clover.
SUMMARY: Red clover, a perennial herb that is prevalent in Asia, Europe, and North America, has traditionally been used to treat skin disorders such as psoriasis and eczema, whooping cough, and mastitis. Red clover contains compounds known as isoflavones that act as phytoestrogens. Isoflavones have generated considerable interest in the last decade because of their possible cancer-preventive, cardioprotective, and anti-osteoporotic effects, as well as for their ability to relieve menopausal symptoms. Red clover supplements are available as capsules, tablets, tinctures, and teas.
Data from clinical trials suggest that supplementation with red clover isoflavones helps relieve menopausal symptoms.[1,2,3] However, conclusions from systematic reviews have been conflicting: one suggested marginal benefit, whereas another found no evidence of effectiveness. In other studies, red clover isoflavones reduced bone loss and improved arterial compliance (the latter is an index of the elasticity of large arteries, an important cardiovascular risk factor).
In vitro, red clover extract acts as an estrogen agonist and stimulates proliferation of estrogen receptor–positive breast cancer cells. However, the red clover isoflavone biochanin A was shown to inhibit aromatase activity and expression, thereby conferring a protective effect. Another recent study found that red clover inhibited the growth of normal prostate cells and increased the resistance of prostate cancer cells to high-dose radiation in vitro. Further research is needed to determine the safety and efficacy of this agent.
CONTRAINDICATIONS AND ADVERSE REACTIONS: Patients with hormone-sensitive cancers should avoid red clover because of its estrogenic activity. Also, red clover may increase the effects of anticoagulants and antiplatelet drugs.
Subarachnoid hemorrhage was reported in a 53-year-old woman following use of an herbal supplement that contained red clover, dong quai, and Siberian ginseng, which she took for hot flashes associated with perimenopause. Her symptoms resolved after discontinuation of the supplement.
1. Lukaczer D, Darland G, Tripp M, et al. Clinical effects of a proprietary combination isoflavone nutritional supplement in menopausal women: a pilot trial. Altern Ther Health Med. 2005;11:60-65.
2. Hidalgo LA, Chedraui PA, Morocho N, et al. The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Gynecol Endocrinol. 2005;21:257-64.
3. van de Weijer PH, Barentsen R. Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas. 2002;42:187-93.
4. Coon JT, Pittler MH, Ernst E. Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. Phytomedicine. 2007;14:153-59.
5. Lethaby AE, Brown J, Marjoribanks J, et al. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev. 2007(4):CD001395.
6. Atkinson C, Compston JE, Day NE, et al. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2004;79:326-33.
7. Nestel PJ, Pomeroy S, Kay S, et al. Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women. J Clin Endocrinol Metab. 1999;84:895-98.
8. Le Bail JC, Champavier Y, Chulia AJ, Habrioux G. Effects of phytoestrogens on aromatase, 3beta and 17beta-hydroxysteroid dehydrogenase activities and human breast cancer cells. Life Sci. 2000;66:1281-91.
9. Wang Y, Man Gho W, Chan FL, et al. The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression. Br J Nutr. 2008;99:303-10.
10. Hasan Y, Schoenherr D, Martinez AA, et al. Prostate-specific natural health products (dietary supplements) radiosensitize normal prostate cells. Int J Radiat Oncol Biol Phys. 2010;76:896-904.
11. Friedman JA, Taylor SA, McDermott W, Alikhani P. Multifocal and recurrent subarachnoid hemorrhage due to an herbal supplement containing natural coumarins. Neurocrit Care. 2007;7:76-80.