Clover / Red Clover (Trifolium pratense) Research

Latin Name: Trifolium pratense

Family: Fabaceae

Red Clover is useful as an herb for menopausal symptoms.  It also shows a potential cholesterol lowering effect.

RESEARCH

The listings of research below represents a compilation of scientific articles found on the species, with a very brief overview description of each article/study.  Research found is catalogued by therapeutic action.  This categorized compilation of research articles does not necessarily imply that there are adequate results to demonstrate safe and/or effective human use.

GENERAL

• Petersen, D. (2016)  Course Material: Herb502: Red Clover Monograph.  www.achs.edu
• Natural Standard (2016).  Red Clover Monograph.  www.naturalstandard.com

SAFETY

• Avoid use during pregnancy due to high isoflavone content (ACHS, 2017).
• May increase the risk of bleeding and interfere with anticoagulant medications and aspirin due to coumarin and isoflavone content (Natural Standard, 2016).
• May interfere with antiretroviral drugs (Natural Standard, 2016).
• May interfere with oral contraceptives and other estrogen containing medications (Natural Standard, 2016).
• May lower blood sugar and interfere with diabetic medications (Natural Standard, 2016).
• Red clover may interfere with how drugs are metabolized in the liver (Natural Standard, 2016).
• Possible adverse interactions with the following diseases.  Contact your physician before use: breast cancer, hormone cancers, hormone conditions, coagulant disorders, protein deficiency, and surgery (Natural Standard, 2016).

MENOPAUSAL SYMPTOMS  / ESTROGEN EFFECT

• Seventeen articles were reviewed and the mega-analysis concluded a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women with no adverse side effects for short term use and no evidence on long term use.  From:  Coon, J. T., Pittler, M. H., & Ernst, E. (2007). Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. Phytomedicine, 14(2), 153-159.
• A meta-analysis of multiple studies on the use of 80 mg a day of isoflavones (for 3 months) from red clover to treat menopause showed a safe and clinically significant benefit to reducing hot flashes.  From:  Myers, S. P., & Vigar, V. (2017). Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80 mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis. Phytomedicine, 24, 141-147.
• This clinical randomized, triple-blind trial was conducted on 72 menopausal women demonstrated that red clover isoflavones reduced menopausal symptoms.  From:  Salehi, K., Ehsanpour, S., Zolfaghari, B., Salehi, Z., & Honargoo, M. (2013). Effect of red clover Isoflavones extract on menopausal symptoms. Journal of Gorgan University of Medical Sciences, 15(2).
• In a double blind study of 60 menopausal women, isoflavones from red clover at 80 mg a day for 90 days significantly reduced menopausal symptoms, including vaginal cytology and triglycerides.  From:  Hidalgo, L. A., Chedraui, P. A., Morocho, N., Ross, S., & San Miguel, G. (2005). The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Gynecological Endocrinology, 21(5), 257-264.
  Red clover extract had a mild estrogenic effect in rats.From:  Burdette, J. E., Liu, J., Lantvit, D., Lim, E., Booth, N., Bhat, K. P., … & Farnsworth, N. R. (2002). Trifolium pratense (red clover) exhibits estrogenic effects in vivo in ovariectomized Sprague-Dawley rats. The Journal of nutrition, 132(1), 27-30.
• Hot flashes were reduced with a supplement of red clover isoflavones in menopausal women.  From:  van de Weijer, P. H., & Barentsen, R. (2002). Isoflavones from red clover (Promensil®) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas, 42(3), 187-193.

MEN’S HEALTH

• Red clover  isoflavones reduced non-malignant prostatic growth in mice by acting as anti-androgenic agents. From:  Jarred, R. A., McPherson, S. J., Jones, M. E., Simpson, E. R., & Risbridger, G. P. (2003). Anti‐androgenic action by red clover‐derived dietary isoflavones reduces non‐malignant prostate enlargement in aromatase knockout (arko) mice. The Prostate, 56(1), 54-64.

REDUCED BONE LOSS

• Isoflavones reduced lumbar spine bone loss in women.  From:  Atkinson, C., Compston, J. E., Day, N. E., Dowsett, M., & Bingham, S. A. (2004). The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial1-3. The American Journal of clinical nutrition, 79(2), 326-333
• Red clover isoflavones were effective in reducing bone loss in rats. From:  Occhiuto, F., Pasquale, R. D., Guglielmo, G., Palumbo, D. R., Zangla, G., Samperi, S., … & Circosta, C. (2007). Effects of phytoestrogenic isoflavones from red clover (Trifolium pratense L.) on experimental osteoporosis. Phytotherapy Research, 21(2), 130-134.
• Bone density improved after women took extracts of isoflavones from red clover.  From:  Clifton-Bligh, P. B., Baber, R. J., Fulcher, G. R., Nery, M. L., & Moreton, T. (2001). The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause, 8(4), 259-265.

ALOPECIA

• Topical application of red clover extract and biomimetic peptide increased hair growth in those with alopecia.  From:  Loing, E., Lachance, R., Ollier, V., & Hocquaux, M. (2013). A new strategy to modulate alopecia using a combination of two specific and unique ingredients. J. Cosmet. Sci, 64(1), 45-58.

​MASTALGIA

• Women showed reduced mastalgia with isoflavone supplements.   From:  Ingram, D. M., Hickling, C., West, L., Mahe, L. J., & Dunbar, P. M. (2002). A double-blind randomized controlled trial of isoflavones in the treatment of cyclical mastalgia. The Breast, 11(2), 170-174.

ANTI-CANCER

• Biochanin, an isoflavone isolated from red clover extract, inhibited breast cancer cell expression in vitro.  From:  Wang, Y., Gho, W. M., Chan, F. L., Chen, S., & Leung, L. K. (2008). The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression. British Journal of Nutrition, 99(02), 303-310.
• Isoflavone derivatives, biochanin A and genistein inhibited the cell growth of stomach cancer cell lines in vitro.  From:  Yanagihara, K., Ito, A., Toge, T., & Numoto, M. (1993). Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract. Cancer Research, 53(23), 5815-5821.
• Dietary isoflavones reduced prostate cancer by inducing apoptosis in low to moderate-grade tumors.  From:  Jarred, R. A., Keikha, M., Dowling, C., McPherson, S. J., Clare, A. M., Husband, A. J., … & Risbridger, G. P. (2002). Induction of apoptosis in low to moderate-grade human prostate carcinoma by red clover-derived dietary isoflavones. Cancer Epidemiology and Prevention Biomarkers, 11(12), 1689-1696
• Coumestrol had a mutagenic, clastogenic effect on cultured human lymphoblastoid cells.  From:  Domon, O. E., McGarrity, L. J., Bishop, M., Yoshioka, M., Chen, J. J., & Morris, S. M. (2001). Evaluation of the genotoxicity of the phytoestrogen, coumestrol, in AHH-1 TK+/− human lymphoblastoid cells. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 474(1), 129-137.

​ANTIMUTAGENIC

• Red clover isoflavones could protect against DNA damage.  From:  Chan, H. Y., Wang, H., & Leung, L. K. (2003). The red clover (Trifolium pratense) isoflavone biochanin A modulates the biotransformation pathways of 7, 12-dimethylbenz [a] anthracene. British journal of nutrition, 90(01), 87-92.

​​CHOLESTEROL LOWERING

• Postmenopausal women with a high BMI showed reduced cholesterol when taking supplement of isoflavones from red clover.  Chedraui, P., San Miguel, G., Hidalgo, L., Morocho, N., & Ross, S. (2008). Effect of Trifolium pratense-derived isoflavones on the lipid profile of postmenopausal women with increased body mass index. Gynecological Endocrinology, 24(11), 620-624.
• Isoflavones reduced triglyceride levels in menopausal women.  From:  Schult, T. M. K., Ensrud, K. E., Blackwell, T., Ettinger, B., Wallace, R., & Tice, J. A. (2004). Effect of isoflavones on lipids and bone turnover markers in menopausal women. Maturitas, 48(3), 209-218.
• Red clover phytoestrogens reduced serum lipid levels in postmenopausal women.  From:  Terzic, M. M., Dotlic, J., Maricic, S., Mihailovic, T., & Tosic‐Race, B. (2009). Influence of red clover‐derived isoflavones on serum lipid profile in postmenopausal women. Journal of Obstetrics and Gynaecology Research, 35(6), 1091-1095.
• Phytoestrogens including estradiol reduced blood cholesterol levels in rabbits.  From:  Asgary, S., Moshtaghian, J., Naderi, G., Fatahi, Z., Hosseini, M., Dashti, G., & Adibi, S. (2007). Effects of dietary red clover on blood factors and cardiovascular fatty streak formation in hypercholesterolemic rabbits. Phytotherapy Research, 21(8), 768-770.

SKIN

• Based on research that estrogen improves skin thickness, collagen, and moisture, a study was conducted in which rats with low estrogen were fed red clover extract with 11% isoflavones and showed improved skin.  From:  Circosta, C., Pasquale, R. D., Palumbo, D. R., Samperi, S., & Occhiuto, F. (2006). Effects of isoflavones from red clover (Trifolium pratense) on skin changes induced by ovariectomy in rats. Phytotherapy research, 20(12), 1096-1099.

CHEMOPREVENTATIVE

• Red clover extract and its isoflavones showed powerful chemopreventive activity in vitro. From:  Krenn, L., & Paper, D. H. (2009). Inhibition of angiogenesis and inflammation by an extract of red clover (Trifolium pratense L.). Phytomedicine, 16(12), 1083-1088.

SUNSCREEN

• The isoflavone: equol, from red clover showed potential as a sunscreen ingredient as tested on hairless rodents.  From:  Widyarini, S., Spinks, N., Husband, A. J., & Reeve, V. E. (2001). Isoflavonoid Compounds from Red Clover (Trifolium pratense) Protect from Inflammation and Immune Suppression Induced by UV Radiation¶. Photochemistry and Photobiology, 74(3), 465-470.

By: Kathy Sadowski

Last Updated: 10/22/18