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Red clover

What is red clover?

Red clover is a plant whose flowers are used to make medicine. Red clover is used for many conditions, but so far there is not enough scientific data to determine whether red clover is effective for any of these conditions. At the very least, red clover does not appear to help with high cholesterol or hot flashes in women. Red clover is used for stomach upset, high cholesterol, whooping cough, cough, asthma, bronchitis and sexually transmitted diseases, as well as to prevent cancer. Some women use red clover for menopausal symptoms such as hot flushes, breast pain or breast tenderness and to relieve the symptoms of premenstrual syndrome. Red clover is applied to the skin for skin cancer, skin ulcers, burns and chronic skin conditions including eczema and psoriasis. An extract of red clover is used as a flavoring agent in foods and beverages. Red clover contains hormone-like substances called isoflavones, which can cause reproductive problems in certain animals. Experts believe that a diet rich in isoflavones may be responsible for reports of reproductive problems and liver disease in cheetahs in zoos. In large quantities, red clover can cause sterility in livestock.

How effective is red clover?

Red clover may be ineffective for the following conditions:

  • High cholesterol levels in women: Scientific research shows that oral intake of red clover for 3 to 12 months in women with moderately elevated cholesterol levels neither lowers levels of bad LDL cholesterol nor increases levels of good HDL cholesterol.
  • Prevention of osteoporosis in women: Scientific research shows that taking an extract of red clover for one year does not appear to improve bone strength in women.
  • Prostate problems such as increased nocturnal urination in men: Scientific research suggests that red clover supplements may improve the symptoms of benign prostatic hyperplasia. Red clover appears to relieve the urge to urinate at night and improve quality of life in men suffering from benign prostatic hyperplasia. However, red clover does not appear to affect the rate of urine flow, PSA levels or the size of the prostate.
  • Prevention of uterine cancer: Scientific research suggests that taking a red clover supplement does not appear to help prevent uterine cancer.
  • Cyclical breast pain: There is evidence that red clover may relieve cyclical breast pain and tension in the breast area.
  • Menopausal symptoms: There are conflicting study results regarding the effects of red clover on menopausal symptoms. Most studies show that taking red clover orally for up to a year does not reduce symptoms such as hot flushes or night sweats. Some studies show that a specific red clover product (Promensil, Novogen) may reduce the severity but not the frequency of hot flushes. Other research shows that another form of red clover (MF11RCE, Melbrosin International) may relieve symptoms of menopause-related anxiety and depression.
  • Stomach upsets
  • Lung problems such as coughs, bronchitis and asthma
  • Sexually transmitted diseases
  • Premenstrual syndrome
  • Skin problems such as skin cancer, burns, eczema and psoriasis

There is not enough scientific data to determine the effectiveness of red clover for the following conditions:

Further research is needed to assess the effectiveness of red clover.

How does red clover work?

Red clover contains isoflavones, which are converted in the body into phytoestrogens, which are similar to the hormone oestrogen.

Are there any safety concerns?

Red clover is probably safe and harmless for most people when used in the amounts found in food. It may be safe when used in medicinal quantities. Red clover can cause skin rashes, muscle aches, headaches, nausea and, in some women, vaginal bleeding. There is not enough scientific information to evaluate the safety of red clover when applied to the skin.

Precautions and warnings

Pregnancy and lactation: Red clover is probably safe and harmless when taken in the amounts usually found in food. However, red clover is probably not safe when taken in medicinal amounts. Red clover acts like estrogen and could disrupt hormonal balance during pregnancy and breastfeeding. For this reason, pregnant and breastfeeding women should avoid red clover. Not enough is known about the safety of red clover applied to the skin during pregnancy and breastfeeding, so pregnant and breastfeeding women should avoid such red clover use to be on the safe side. Bleeding disorders: Red clover could increase the tendency to bleed. For this reason, people who suffer from bleeding disorders should avoid large amounts of red clover. Hormone-sensitive diseases such as breast cancer, uterine cancer, ovarian cancer or endometriosis: Red clover can act like oestrogen. For this reason, red clover should not be used if you suffer from a disease that can be aggravated by oestrogen.

Protein S deficiency: People who suffer from a protein S deficiency have an increased risk of developing blood clots. There are concerns that red clover may increase the risk of developing blood clots in these people because it has some of the effects of estrogen. For this reason, red clover should not be used if you are protein S deficient.

Surgeries: Red clover may slow down blood clotting. It could therefore increase the risk of bleeding during and after operations. For this reason, you should stop taking red clover at least 2 weeks before surgery.

Interactions with medication

Care should be taken when combining red clover with the following medications:

Birth control pills

Some birth control pills contain oestrogen. Red clover may have some of the effects of estrogen. However, the estrogenic effect of red clover is weaker than the estrogenic effect of birth control pills. The use of red clover in combination with birth control pills could reduce the effectiveness of the birth control pill. For this reason, other contraceptives such as condoms should be used when using red clover.

Oestrogens

Large amounts of red clover may have some of the effects of estrogen. However, the oestrogen effect of red clover is weaker than the oestrogen effect of oestrogen tablets. The use of red clover in combination with oestrogen tablets could reduce the effect of oestrogen tablets. Drugs that are broken down by the liver (cytochrome P450 1A2 (CYP1A2) substrates, cytochrome P450 2C19 (CYP2C19) substrates, cytochrome P450 2C9 (CYP2C9) substrates, cytochrome P450 3A4 (CYP3A4) substrates) Some drugs are broken down by the liver. Red clover can reduce the rate at which the liver breaks down certain drugs. Taking red clover in conjunction with drugs that are broken down by the liver may increase the effects and side effects of some of these drugs. For this reason, you should consult your doctor before taking red clover if you are taking medicines that are broken down by the liver.

Medications that slow down blood clotting

Large amounts of red clover could slow down blood clotting. Taking red clover in conjunction with medications that also slow blood clotting could increase the risk of bleeding and the tendency to bruise.

Are there any interactions with medicinal herbs or supplements?

Medicinal herbs and supplements that could slow down blood clotting Red clover could slow down blood clotting. Taking red clover in conjunction with herbs or supplements that may slow blood clotting could increase the risk of bleeding and the tendency to bruise. Some of these medicinal herbs are angelica, clove, garlic, ginger, ginkgo, panax ginseng, horse chestnut, tumeric and others

Medicinal herbs with oestrogen activity

Large amounts of red clover may have the same effect as oestrogen. The use of red clover in combination with other medicinal herbs that have some of the effects of estrogen could enhance or reduce the estrogen-like effects of these other medicinal herbs. Such medicinal herbs include alfalfa, black snake root, flaxseed, hops, ipriflavone, copoubean, licorice, and soy.

Are there any interactions with food?

There are no known interactions with food.

Dosage

An appropriate dosage of red clover depends on various factors such as age, state of health and others. At this time, there is insufficient scientific data to make a statement about appropriate dosage ranges for red clover. For this reason, you should follow the dosage instructions on the label and/or consult a doctor or pharmacist before use.

References

  1. Lipovac M, Chedraui P, Gruenhut C, et al. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts. Maturitas 2010;65:258-61.
  2. Geller SE, Shulman LP, van Breemen RB, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 2009;16:1156-66.
  3. Krebs EE, Ensrud KE, MacDonald R, Wilt TJ. Phytoestrogens for treatment of menopausal symptoms: a systematic review. Obstet Gynecol 2004;104:824-36.
  4. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-71.
  5. Cheong JL, Bucknall R. Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient. Postgrad Med J 2005;81:266-7.
  6. Atkinson C, Warren RM, Sala E, et al. Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]. Breast Cancer Res 2004;6:R170-R179.
  7. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;18:2273-81.
  8. Keinan-Boker L, van Der Schouw YT, Grobbee DE, Peters PH. Dietary phytoestrogens and breast cancer risk. Am J Clin Nutr 2004;79:282-8.
  9. Risbridger GP, Wang H, Frydenberg M, Husband A. The in vivo effect of red clover diet on ventral prostate growth in adult male mice. Reprod Fertil Dev 2001;13:325-9.
  10. Jarred RA, McPherson SJ, Jones ME, et al. Anti-androgenic action by red clover-derived dietary isoflavones reduces non-malignant prostate enlargement in aromatase knockout (ArKo) mice. Prostate 2003;56:54-64.
  11. Geller J, Sionit L, Partido C, et al. Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture. Prostate 1998;34:75-9.
  12. Hale GE, Hughes CL, Robboy SJ, et al. A double-blind randomized study on the effects of red clover isoflavones on the endometrium. Menopause 2001;8:338-46.
  13. Atkinson C, Oosthuizen W, Scollen S, et al. Modest protective effects of isoflavones from a red clover-derived dietary supplement on cardiovascular disease risk factors in perimenopausal women, and evidence of an interaction with ApoE genotype in 49-65 year-old women. J Nutr 2004;134:1759-64.
  14. Roberts DW, Doerge DR, Churchwell MI, et al. Inhibition of extrahepatic human cytochromes P450 1A1 and 1B1 by metabolism of isoflavones found in Trifolium pratense (red clover). J Agric Food Chem 2004;52:6623-32.
  15. Schult TM, Ensrud KE, Blackwell T, et al. Effect of isoflavones on lipids and bone turnover markers in menopausal women. Maturitas 2004;48:209-18.
  16. Tice JA, Ettinger B, Ensrud K, et al. Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) study: a randomized controlled trial. JAMA 2003;290:207-14.
  17. Puschner B, Galey FD, Holstege DM, et al. Sweet clover poisoning in dairy cattle in California. J Am Vet Med Assoc 1998;212:857-9.
  18. Knight DC, Howes JB, Eden JA. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric 1999;2:79-84.
  19. Baber RJ, Templeman C, Morton T, et al. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric 1999;2:85-92.
  20. Horn-Ross PL, John EM, Canchola AJ, et al. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 2003;95:1158-64.
  21. Nelsen J, Barrette E, Tsouronix C, et al. Red clover (Trifolium pratense) monograph: A clinical decision support tool. J Herb Pharmacother 2002;2:49-72.
  22. Ingram DM, Hickling C, West L, et al. A double-blind randomized controlled trial of isoflavones in the treatment of cyclical mastalgia. The Breast 2002;11:170-4.
  23. Anon. The role of isoflavones in menopausal health: consensus opinion of the North American Menopause Society. Menopause 2000;7:215-29.
  24. van de Weijer P, Barentsen R. Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas 2002;42:187-93.
  25. Tice J, Cummings SR, Ettinger B, et al. Few adverse effects of two red clover extracts rich in phytoestrogens: a multicenter, placebo-controlled trial. Alt Ther 2001;7:S33.
  26. 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;8:135-42.
  27. This P, De La Rochefordiere A, Clough K, et al. Phytoestrogens after breast cancer. Endocr Relat Cancer 2001;8:129-34.
  28. Vincent A, Fitzpatrick LA. Soy isoflavones: are they useful in menopause? Mayo Clin Proc 2000;75:1174-84.
  29. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82.
  30. Gerber G, Lowe FC, Spigelman S. The use of a standardized extract of red clover isoflavones for the alleviation of BPH symptoms. Endocrine Soc 82nd Ann Mtg, Toronto, CAN 2000;Jun 21-4:abstract 2359.
  31. 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.
  32. Lissin LW, Cooke JP. Phytoestrogens and cardiovascular health. J Am Coll Cardiol 2000;35:1403-10.
  33. Setchell KD, Cassidy A. Dietary isoflavones: biological effects and relevance to human health. J Nutr 1999;129:758S-67S.
  34. Electronic Code of Federal Regulations. Title 21 Part 182 -- Substances Generally Recognized As Safe. Available at: http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid= 786bafc6f6343634fbf79fcdca7061e1&rgn=div5&view= text&node=21:3.0.1.1.13&idno=21
  35. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr 1997;17:353-81.
  36. Cassady JM, Zennie TM, Chae YH, et al. Use of a mammalian cell culture benzo(a)pyrene metabolism assay for the detection of potential anticarcinogens from natural products: inhibition of metabolism by biochanin A, an isoflavone from Trifolium pratense L. Cancer Res 1988;48:6257-61.
  37. 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.
  38. Yanagihara K, Ito A, Toge T, Numoto M. Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract. Cancer Res 1993;53:5815-21.
  39. Hodgson JM, Puddey IB, Beilin LJ, et al. Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans. J Nutr 1998;128:728-32.
  40. Setchell KD, Gosselin SJ, Welsh MB, et al. Dietary estrogens--a probable cause of infertility and liver disease in captive cheetahs. Gastroenterol 1987;93:225-33.
  41. Hargreaves DF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 1999;84:4017-24.
  42. Anthony MS. Soy and cardiovascular disease: cholesterol lowering and beyond. J Nutr 2000;130:662S-3S.
  43. Ginsburg J, Prelevic GM. Lack of significant hormonal effects and controlled trials of phyto-oestrogens. Lancet 2000;355:163-4.
  44. Duncan AM, Underhill KE, Xu X, et al. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab 1999;84:3479-84.
  45. Baird DD, Umbach DM, Lansdell L, et al. Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women. J Clin Endocrinol Metab 1995;80:1685-90.
  46. Barnes S, Kim H, Darley-Usmar V, et al. Beyond ERalpha and ERbeta: Estrogen receptor binding is only part of the isoflavone story. J Nutr 2000;130:656S-7S.
  47. Setchell KD. Absorption and metabolism of soy isoflavones-from food to dietary supplements and adults to infants. J Nutr 2000;130:654S-5S.
  48. Zand RS, Jenkins DJ, Diamandis EP. Steroid hormone activity of flavonoids and related compounds. Breast Cancer Res Treat 2000;62:35-49.
  49. Umland EM, Cauffield JS, Kirk JK, et al. Phytoestrogens as therapeutic alternatives to traditional hormone replacement in postmenopausal women. Pharmacotherapy 2000;20:981-90.
  50. Howes JB, Sullivan D, Lai N, et al. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of postmenopausal women with mild to moderate hypercholesterolemia. Atherosclerosis 2000;152:143-7.
  51. 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;84:895-8.