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  • Red Clover

    En Español (Spanish Version) Trifolium pratense

    Principal Proposed Uses

    Menopausal Symptoms

    Other Proposed Uses

    Acne ; Cyclic Mastalgia ; Eczema ; Enhancing Mental Function ; High Blood Pressure ; High Cholesterol ; Osteoporosis ; Psoriasis

    Red clover has been cultivated since ancient times, primarily to provide a favorite grazing food for animals. But, like many other herbs, red clover was also a valued medicine. Although it has been used for many purposes worldwide, the one condition most consistently associated with red clover is cancer. Chinese physicians and Russian folk healers also used it to treat respiratory problems.

    In the nineteenth century, red clover became popular among herbalists as an "alternative" or "blood purifier." This medical term, long since defunct, refers to an ancient belief that toxins in the blood are the root cause of many illnesses. Cancer, eczema, and the eruptions of venereal disease were all seen as manifestations of toxic buildup.

    Red clover was considered one of the best herbs to "purify" the blood. For this reason, it is included in many of the famous treatments for cancer, including Jason Winter's cancer-cure tea.

    Recently, special red clover extracts high in substances called isoflavones have arrived on the market. These isoflavones produce effects in the body somewhat similar to those of estrogen, and for this reason they are called phytoestrogens ("phyto" indicates a plant source). The major isoflavones in red clover include genistein and daidzen, also found in soy, as well as formononetin and biochanin.

    What Is Red Clover Used for Today?

    Evidence is inconsistent on whether red clover isoflavones are helpful for menopausal hot flashes,1,2,7,10,15 with the largest trial failing to find benefits.10

    A small and poorly reported double-blind, placebo-controlled study provides weak evidence that red clover isoflavones might be helpful for cyclic mastalgia.6

    Although soy and, possibly, soy isoflavones 8 have been found to reduce cholesterol levels, two trials enrolling a total of more than 100 women failed to find red clover isoflavones helpful for this purpose.3,9 However, in a double-blind, placebo-controlled comparative study of 80 people (both men and women), a red clover extract modified to be rich in biochanin did reduce LDL (“bad”) cholesterol, while one enriched in formononetin did not.11

    One very small double-blind study found hints that red clover isoflavones might slightly improve blood pressure in post-menopausal women with diabetes.12

    Preliminary evidence suggests that red clover isoflavones may help prevent or treat osteoporosis.13

    In a 6-month, double-blind study, use of red clover isoflavones failed to enhance or harm mental function.14

    There is no evidence that red clover can help treat cancer. However, its usage in many parts of the world as a traditional cancer remedy has prompted scientists to take a close look at the herb. It turns out that the isoflavones in red clover may possess anti-tumor activity in the test tube.4,5 However, such preliminary research does not prove that red clover can treat cancer.

    Red clover is sometimes recommended for the treatment of acne, eczema, psoriasis, and other skin diseases.

    What is the Scientific Evidence for Red Clover

    Menopausal Hot Flashes

    In a 12-week, double-blind, placebo-controlled trial of 30 post-menopausal women, use of red clover isoflavones at a dose of 80 mg daily significantly reduced hot flash symptoms as compared to placebo.7 Benefits were also seen in a 90-day study of 60 post-menopausal women given placebo or 80 mg of red clover isoflavones.10 However, a much larger study (252 participants) failed to find benefit with 82 or 57 mg of red clover isoflavones daily.10

    Two other studies also failed to find benefit. One, a 28-week, double-blind, placebo-controlled crossover study of 51 post-menopausal women, found no reduction in hot flashes among those given 40 mg of red clover isoflavones daily.1 No benefits were seen in another double-blind, placebo-controlled trial, which involved 37 women given isoflavones from red clover at a dose of either 40 or 160 mg daily.2

    Dosage

    A typical dosage of red clover extract provides 40 to 160 mg of isoflavones daily. In the positive study described above, 80 mg daily were sufficient to reduce menopausal hot flashes.

    Safety Issues

    Red clover is on the Food and Drug Administration's Generally Recognized as Safe (GRAS) list and is included in many beverage teas. However, detailed safety studies have not been performed.

    Because of its blood-thinning and estrogen-like constituents, red clover should not be used by pregnant or nursing women, or women who have had breast or uterine cancer. A study investigating the safety of red clover in women with a family history of breast cancer found no changes in breast density or thickness of the uterine lining over a three-year period, which is somewhat reassuring.17 However, the study was much too short to determine red clover's long-term effect on cancer risk. Safety in young children or those with severe liver or kidney disease has also not been established.

    Based on their constituents, red clover extracts may conceivably interfere with hormone treatments and anticoagulant drugs (see the next section for specific drugs).

    One double-blind study of post-menopausal women found the use of red clover isoflavones at a dose of 80 mg daily for 90 days resulted in increased levels of testosterone.16 The potential significance of this is unclear. The same study found that red clover isoflavones reduced the thickness of the uterine lining, a finding that suggests low possibility for endometrial cancer.

    For other potential risks due to the isoflavones in red clover (especially in concentrated isoflavone-rich extracts of red clover), see the full article on Isoflavones.

    Interactions You Should Know About

    References

    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.

    Knight DC, Howes JB, Eden JA. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric. 1999;2:79-84.

    Howes JB, Sullivan D, Lai N, et al. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia. Atherosclerosis. 2000;152:143-147.

    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;48:6257-6261.

    Yanagihara K, Ito A, Toge T, et al. Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract. Cancer Res. 1993;53:5815-5821.

    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;11:170-174.

    van de Weijer P, Barentsen R. Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas. 2002;42:18.

    Messina M, Gardner C, Barnes S. Gaining insight into the health effects of soy but a long way still to go: commentary on the fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. J Nutr. 2002;132:547S-551S.

    Blakesmith SJ, Lyons-Wall PM, George C, et al. Effects of supplementation with purified red clover ( Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal women. Br J Nutr. 2003;89:467-475.

    Tice JA, Ettinger B, Ensrud K, et al. Phytoestrogen supplements for the treatment of hot flashes: The Isoflavone Clover Extract (ICE) Study. JAMA. 2003;290:207-214.

    Nestel P, Cehun M, Chronopoulos A, et al. A biochanin-enriched isoflavone from red clover lowers LDL cholesterol in men. Eur J Clin Nutr. 2004;58:403-408.

    Howes JB, Tran D, Brillante D, et al. Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes. Diabetes Obes Metab. 2003;5:325-332.

    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;79:326-333.

    Howes JB, Bray K, Lorenz L, et al. The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women. Climacteric. 2004;7:70-77.

    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;21:257-264.

    Imhof M, Gocan A, Reithmayr F et al. Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women. Maturitas. 2006 Feb 28 [Epub ahead of print].

    Powles TJ, Howell A, Evans DG, et al. Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int. 2008;14:6-12.

    Last reviewed July 2012 by EBSCO CAM Review Board

    Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

    Copyright © EBSCO Publishing. All rights reserved.

  • Red Clover

    En Español (Spanish Version) Trifolium pratense

    Principal Proposed Uses

    Menopausal Symptoms

    Other Proposed Uses

    Acne ; Cyclic Mastalgia ; Eczema ; Enhancing Mental Function ; High Blood Pressure ; High Cholesterol ; Osteoporosis ; Psoriasis

    Red clover has been cultivated since ancient times, primarily to provide a favorite grazing food for animals. But, like many other herbs, red clover was also a valued medicine. Although it has been used for many purposes worldwide, the one condition most consistently associated with red clover is cancer. Chinese physicians and Russian folk healers also used it to treat respiratory problems.

    In the nineteenth century, red clover became popular among herbalists as an "alternative" or "blood purifier." This medical term, long since defunct, refers to an ancient belief that toxins in the blood are the root cause of many illnesses. Cancer, eczema, and the eruptions of venereal disease were all seen as manifestations of toxic buildup.

    Red clover was considered one of the best herbs to "purify" the blood. For this reason, it is included in many of the famous treatments for cancer, including Jason Winter's cancer-cure tea.

    Recently, special red clover extracts high in substances called isoflavones have arrived on the market. These isoflavones produce effects in the body somewhat similar to those of estrogen, and for this reason they are called phytoestrogens ("phyto" indicates a plant source). The major isoflavones in red clover include genistein and daidzen, also found in soy, as well as formononetin and biochanin.

    What Is Red Clover Used for Today?

    Evidence is inconsistent on whether red clover isoflavones are helpful for menopausal hot flashes,1,2,7,10,15 with the largest trial failing to find benefits.10

    A small and poorly reported double-blind, placebo-controlled study provides weak evidence that red clover isoflavones might be helpful for cyclic mastalgia.6

    Although soy and, possibly, soy isoflavones 8 have been found to reduce cholesterol levels, two trials enrolling a total of more than 100 women failed to find red clover isoflavones helpful for this purpose.3,9 However, in a double-blind, placebo-controlled comparative study of 80 people (both men and women), a red clover extract modified to be rich in biochanin did reduce LDL (“bad”) cholesterol, while one enriched in formononetin did not.11

    One very small double-blind study found hints that red clover isoflavones might slightly improve blood pressure in post-menopausal women with diabetes.12

    Preliminary evidence suggests that red clover isoflavones may help prevent or treat osteoporosis.13

    In a 6-month, double-blind study, use of red clover isoflavones failed to enhance or harm mental function.14

    There is no evidence that red clover can help treat cancer. However, its usage in many parts of the world as a traditional cancer remedy has prompted scientists to take a close look at the herb. It turns out that the isoflavones in red clover may possess anti-tumor activity in the test tube.4,5 However, such preliminary research does not prove that red clover can treat cancer.

    Red clover is sometimes recommended for the treatment of acne, eczema, psoriasis, and other skin diseases.

    What is the Scientific Evidence for Red Clover

    Menopausal Hot Flashes

    In a 12-week, double-blind, placebo-controlled trial of 30 post-menopausal women, use of red clover isoflavones at a dose of 80 mg daily significantly reduced hot flash symptoms as compared to placebo.7 Benefits were also seen in a 90-day study of 60 post-menopausal women given placebo or 80 mg of red clover isoflavones.10 However, a much larger study (252 participants) failed to find benefit with 82 or 57 mg of red clover isoflavones daily.10

    Two other studies also failed to find benefit. One, a 28-week, double-blind, placebo-controlled crossover study of 51 post-menopausal women, found no reduction in hot flashes among those given 40 mg of red clover isoflavones daily.1 No benefits were seen in another double-blind, placebo-controlled trial, which involved 37 women given isoflavones from red clover at a dose of either 40 or 160 mg daily.2

    Dosage

    A typical dosage of red clover extract provides 40 to 160 mg of isoflavones daily. In the positive study described above, 80 mg daily were sufficient to reduce menopausal hot flashes.

    Safety Issues

    Red clover is on the Food and Drug Administration's Generally Recognized as Safe (GRAS) list and is included in many beverage teas. However, detailed safety studies have not been performed.

    Because of its blood-thinning and estrogen-like constituents, red clover should not be used by pregnant or nursing women, or women who have had breast or uterine cancer. A study investigating the safety of red clover in women with a family history of breast cancer found no changes in breast density or thickness of the uterine lining over a three-year period, which is somewhat reassuring.17 However, the study was much too short to determine red clover's long-term effect on cancer risk. Safety in young children or those with severe liver or kidney disease has also not been established.

    Based on their constituents, red clover extracts may conceivably interfere with hormone treatments and anticoagulant drugs (see the next section for specific drugs).

    One double-blind study of post-menopausal women found the use of red clover isoflavones at a dose of 80 mg daily for 90 days resulted in increased levels of testosterone.16 The potential significance of this is unclear. The same study found that red clover isoflavones reduced the thickness of the uterine lining, a finding that suggests low possibility for endometrial cancer.

    For other potential risks due to the isoflavones in red clover (especially in concentrated isoflavone-rich extracts of red clover), see the full article on Isoflavones.

    Interactions You Should Know About

    References

    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.

    Knight DC, Howes JB, Eden JA. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric. 1999;2:79-84.

    Howes JB, Sullivan D, Lai N, et al. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia. Atherosclerosis. 2000;152:143-147.

    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;48:6257-6261.

    Yanagihara K, Ito A, Toge T, et al. Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract. Cancer Res. 1993;53:5815-5821.

    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;11:170-174.

    van de Weijer P, Barentsen R. Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas. 2002;42:18.

    Messina M, Gardner C, Barnes S. Gaining insight into the health effects of soy but a long way still to go: commentary on the fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. J Nutr. 2002;132:547S-551S.

    Blakesmith SJ, Lyons-Wall PM, George C, et al. Effects of supplementation with purified red clover ( Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal women. Br J Nutr. 2003;89:467-475.

    Tice JA, Ettinger B, Ensrud K, et al. Phytoestrogen supplements for the treatment of hot flashes: The Isoflavone Clover Extract (ICE) Study. JAMA. 2003;290:207-214.

    Nestel P, Cehun M, Chronopoulos A, et al. A biochanin-enriched isoflavone from red clover lowers LDL cholesterol in men. Eur J Clin Nutr. 2004;58:403-408.

    Howes JB, Tran D, Brillante D, et al. Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes. Diabetes Obes Metab. 2003;5:325-332.

    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;79:326-333.

    Howes JB, Bray K, Lorenz L, et al. The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women. Climacteric. 2004;7:70-77.

    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;21:257-264.

    Imhof M, Gocan A, Reithmayr F et al. Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women. Maturitas. 2006 Feb 28 [Epub ahead of print].

    Powles TJ, Howell A, Evans DG, et al. Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int. 2008;14:6-12.

    Last reviewed July 2012 by EBSCO CAM Review Board

    Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

    Copyright © EBSCO Publishing. All rights reserved.

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