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Red Clover

Red Clover

Common Names

  • Cow clover
  • Wild clover
  • Purple clover beebread
  • Cow grass
  • Meadow clover
  • Purple clover

For Patients & Caregivers

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Red clover may help reduce menopausal symptoms.

Red clover contains compounds known as isoflavones (also found in soy) that show estrogenic activity in laboratory experiments. The isoflavones in red clover include biochanin, daidzein, formononetin and genistein. However, when used in the body, the effects of red clover isoflavones are less clear. They seem to have estrogenic activity, but so far have not been found to relieve menopausal symptoms or cause the endometrium to grow. A study of menopausal women found that red clover extract improved the elasticity of major arteries. Loss of elasticity may occur through menopause. This can contribute to increases in blood pressure that cause the heart to work harder. However, it is not known if red clover can protect against the development of heart disease, and this will require more clinical trials.

In laboratory experiments, red clover extract can stimulate the production of estrogen receptor-positive breast cancer cells, indicating that this herb may not be helpful for women with estrogen-sensitive cancers. Red clover was also shown to stop the growth of normal prostate cells and increase resistance of prostate cancer cells to high-dose radiation in lab experiments.

Patients should avoid the use of red clover during radiotherapy for prostate cancer, or if you have estrogen receptor-positive cancers.

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  • To relieve chest congestion
    There are no data to support this use.
  • To relieve the symptoms of menopause
    The red clover product Promensil® was no better than placebo in treating menopausal symptoms.
  • To prevent heart disease in post-menopausal women
    A few clinical trials have looked at the effects of red clover on development of risk factors for heart disease in postmenopausal women, with no strong evidence that it helps. Most studies found that red clover had no effect on blood cholesterol or triglyceride levels. One clinical trial found that red clover increased the elasticity of major arteries, which may help prevent a gradual rise in blood pressure that can contribute to heart disease.
  • To stop muscle spasms
    No scientific evidence supports this claim.
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  • You are taking warfarin or other blood thinners: Red clover can increase the risk of bleeding.
  • You have a hormone-sensitive disease such as estrogen receptor-positive breast cancer, ovarian cancer, endometriosis, or others: Red clover may have estrogenic activity and should be avoided or used cautiously by patients with these estrogen-sensitive diseases.
  • You are taking methotrexate: Red clover may cause toxic effects, including severe vomiting and pain in the upper abdomen.
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  • Case report: Intracranial hemorrhage was reported in a 53-year-old woman following use of an herbal supplement containing red clover, dong quai, and Siberian ginseng for hot flashes associated with perimenopause. Her symptoms resolved after discontinuing use of the supplement.
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For Healthcare Professionals

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Promensil®, Rimonstil®
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Trifolium pratense
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Red clover is a perennial herb traditionally used to treat skin disorders such as psoriasis and eczema, whooping cough, and mastitis. It contains compounds known as isoflavones that act as phytoestrogens. An isoflavone extracts is widely promoted as a dietary supplement to relieve menopausal symptoms.

Red clover extract was shown to act as an estrogen agonist and to stimulate proliferation of ER-positive breast cancer cells in vitro (1). However, Biochinin A, an isoflavone, inhibited aromatase activity and expression (2), thereby conferring a protective effect. In other studies, isoflavone-enriched extracts demonstrated neuroprotective effects in human cortical neurons (3) (4) and reduced skin aging in mice by increasing the amount of collagen (5).

Clinical data show that supplementation with red clover isoflavones  improves menopausal symptoms compared to placebo (6) (7) (8). But conclusions from systematic reviews are conflicting: two suggest benefit whereas the third found no evidence of effectiveness (9) (24) (10). In postmenopausal women, supplementation was shown to alleviate vasomotor and menopausal symptoms (18) (25). Isoflavones may also improve bone loss (11). In a trial involving ostopenic postmenopausal women, a red clover extract rich in isoflavone aglycones and probiotics attenuated bone mineral density loss caused by estrogen deficiency and improved bone turnover (26). Dietary isoflavone intake also improved arterial compliance, an index of the elasticity of large arteries, which is an important cardiovascular risk factor (12).

Of concern are findings that red clover inhibits the growth of normal prostate cells and increases resistance of prostate cancer cells to high-dose radiation, in vitro (15). Patients should consult with their physicians before taking red clover supplements.

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  • Chest congestion
  • Menopausal symptoms
  • Spasms
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Formononetin, an isoflavone, induced apoptosis in human breast cancer cells by activating the Ras-p38 mitogen-activated protein kinase in ER-positive breast cancer cells (23). It also inhibited the proliferation of human osteosarcoma U2SO cells by decreasing the expression of Bcl-2 (apoptotic repressor) and miR-375, while increasing Bax (a pro-apoptotic protein) (27). Biochanin A, another isoflavone had inhibitory effects on the activity and gene expression of aromatase, an enzyme that catalyzes the conversion of androgen to estrogen (2). In addition, it protected dopaminergic neurons against lipopolysaccharide-induced damage via inhibition of microglial activation and generation of pro-inflammatory factors (3). An isoflavone-enriched fraction showed neuroprotective activity in human cortical neurons as well, which is thought to be due to antioxidant and estrogenic effects (4).

In a murine model, red clover isoflavones reduced skin aging induced by estrogen deprivation following ovariectomy (5).

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  • Patients with hormone-sensitive cancers should avoid red clover because it has estrogenic activity (21).
  • Red clover may increase the effects of anticoagulants and antiplatelet drugs (20).
  • Red clover causes toxic effects when used with methotrexate (19).
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  • Case report: Subarachnoid hemorrhage was reported in a 53-year-old woman following use of an herbal supplement containing red clover, dong quai, and Siberian ginseng for hot flashes associated with perimenopause. Her symptoms resolved after discontinuing use of the supplement (16).
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Anticoagulants / Antiplatelets: Red clover may increase their effects (20).
Cytochrome P450 enzymes: Red clover can inhibit CYP1A2/2C8/2C9/2C19/2D6 and 3A4, and may interact with substances metabolized by these enzymes (17) (28)
Methotrexate: Red clover has been reported to cause toxicity, resulting in severe vomiting and epigastric pain, when used along with methotrexate injections (19).

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  1. Wang Y, Man Gho W, Chan FL, Chen S, Leung LK. The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression. Br J Nutr 2008;99(2):303-310.

  2. Circosta C, De Pasquale R, Palumbo DR, Samperi S, Occhiuto F. Effects of isoflavones from red clover (Trifolium pratense) on skin changes induced by ovariectomy in rats. Phytother Res 2006;20(12):1096-1099.

  3. 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(5):60-65.

  4. Lethaby AE, Brown J, Marjoribanks J, Kronenberg F, Roberts H, Eden J. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2007(4):CD001395.

  5. Atkinson C, Compston JE, Day NE, Dowsett M, Bingham SA. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2004;79(2):326-333.

  6. 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(3):895-898.

  7. Tava A, Ramella D, Grecchi M, et al.Volatile constituents of Trifolium pratense and T. repens from N.E. Italian alpine pastures. Nat Prod Commun. 2009 Jun;4(6):835-8.

  8. 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 Mar 1;76(3):896-904.

  9. 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(1):76-80.

  10. Lipovac M, Chedraui P, Gruenhut C, et al. The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women. Gynecol Endocrinol. 2012 Mar;28(3):203-7.

  11. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000 Jul 1;57(13):1221-7.

  12. Booth NL, Overk CR, Yao P, et al. The chemical and biologic profile of a red clover (Trifolium pratense L.) phase II clinical extract. J Altern Complement Med. 2006 Mar;12(2):133-9.

  13. Howes J, Waring M, Huang L, Howes LG. Long-term pharmacokinetics of an extract of isoflavones from red clover (Trifolium pratense). J Altern Complement Med. 2002 Apr;8(2):135-42.

  14. Shakeri F, Taavoni S, Goushegir A, Haghani H. Effectiveness of red clover in alleviating menopausal symptoms: a 12-week randomized, controlled trial. Climacteric. 2015;18(4):568-73.

  15. Arora S, Taneja I, Challagundla M, Raju KS, Singh SP, Wahajuddin M. In vivo prediction of CYP-mediated metabolic interaction potential of formononetin and biochanin A using in vitro human and rat CYP450 inhibition data. Toxicol Lett. 2015 Nov 19;239(1):1-8.

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Email your questions and comments to aboutherbs@mskcc.org.

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