Red Clover Herb, extract and blossom health benefit, side effects, for menopause, hot flashes - Trifolium pratense
September 1 2017 by Ray Sahelian, M.D.

Red clover herb is a native plant of Europe, central Asia, and northern Africa. The flower head is the part of the plant used in herbal remedies. Scientists have identified estrogen-like substances called isoflavones and anticoagulant chemicals called coumarins in red clover herb. Red Clover is found in many herbal formulas for menopause. Although the benefits of red clover herb are controversial, recent studies do point to potential benefit from the use of this herb for menopausal issues.

Red clover benefit research
The benefit of red clover for reducing severity of hot flashes is hotly debated in the scientific community with some studies showing benefits whereas others have not shown this herb to be effective.

Hot flashes
Avicenna J Phytomed. 2015. Effects of red clover on hot flash and circulating hormone concentrations in menopausal women: a systematic review and meta-analysis. To critically evaluate the effect of red clover on hot flash, endometrial thickness, and hormones status in postmenopausal and peri- and post-menopausal women. Red clover had a positive effect of alleviating hot flash in menopausal women. Our data, however, suggested very slight changes in FSH, LH, testosterone, and Sex hormone-binding globulin SHBG and significant effect in estrogen status by red clover consumption. However, the interpretation of results of the current study is limited due to methodological flaws of the included studies, menopause status, and large heterogeneity among them.

To investigate the benefit of a red clover isoflavone dietary supplement Promensil versus placebo on the change in hot flush frequency in postmenopausal women, a randomized, double blind, placebo-controlled trial was done at Vrije University Medical Center in Amsterdam, The Netherlands. Women with more than 12 months without periods and experiencing more than five flushes per day were enrolled. All received placebo tablets for 4 weeks and were subsequently randomized to either placebo or 80 mg isoflavones from red clover for a further 12 weeks. Improvement was measured by the decrease in number of hot flushes per day. During the first 4 weeks of placebo the frequency of hot flushes decreased by 16%. During the subsequent double blind phase, a further, statistically significant decrease of 44% was seen in the red clover isoflavone group, whereas no further reduction occurred within the placebo group.
   Dr. Sahelian says: In this study, treatment with 80 mg red clover isoflavones per day resulted in a significant reduction in hot flushes from baseline. Since long-term hormone replacement with Premarin and synthetic progestins now appears to increase the risk for cancer, heart disease and blood clots, more women are searching for herbal alternatives to treating menopausal and postmenopausal symptoms. The research with red clover is still early and not all studies have shown that it reduces hot flashes in any significant way, but it does seem to have a mild effect.

The isoflavone irilone contributes to the estrogenic potential of dietary supplements containing red clover. Arch Toxicol. 2013.

Clin Exp Obstetrics Gynecology. 2013. Nonhormonal management of postmenopausal women: effects of a red clover based isoflavones supplementation on climacteric syndrome and cardiovascular risk serum profile. The aim of this prospective randomized study was to evaluate a red clover based isoflavones supplementation in the treatment of climacteric syndrome and its effects on cardiovascular risk serum profile. The study included 150 healthy postmenopausal women that were randomly assigned to receive phytoestrogens tablets, amounting in a total daily intake of 60 mg red clover isoflavones plus 19 mg soy isoflavones, or placebo. The authors evaluated teh following: daily number of hot flushes and Kupperman Index at baseline and after one and three months; serum total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and antithrombin III (ATIII) at baseline and after three and six months. One hundred twenty-eight patients completed the study: 67 in the active group and 61 in the placebo group. The treatment led to a progressive significant reduction of the number of hot flushes in the active group compared to placebo already after one month, while Kupperman Index was statistically reduced after three months. No significant variation in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, PT, PTT, fibrinogen, and ATIII were found. The present findings suggest that a red clover based isoflavones supplementation in healthy postmenopausal women is promptly effective on climacteric syndrome, improves neurovegetative symptoms, safe on cardiovascular risk serum profile, and does not modify lipids and coagulation.

Anxiety and depression
A study investigated the effects of isoflavones from red clover extracts on anxiety and depressive symptoms. Researchers recruited postmenopausal women aged 40 and over. The women were randomly administered 80 mg twice daily of red clover isoflavones or a placebo for 90 days. Then the medication was crossed over and taken for another 90 days. Women in the red clover extract group experienced a significant reduction in anxiety and depressive symptoms while the women in the placebo group experienced only minimal reductions. Red clover isoflavones were effective in reducing anxiety and depressive symptoms. 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;

Benefit of red clover herb for blood pressure and bone density
Red clover may also benefit bone density and reduce blood pressure. One study shows red clover has an effect on lowering cholesterol although not all studies have been consistent in this regard. Red clover has been shown in lab studies to reduce the risk for prostate cancer.

Red clover and cholesterol, blood lipids
Effect of Trifolium pratense-derived isoflavones on the lipid profile of postmenopausal women with increased body mass index.
Gynecol Endocrinol. 2008.
We determined the effect of red clover derived isoflavone supplementation on the lipid profile of postmenopausal women with increased body mass index (BMI). Sixty postmenopausal women aged 40 years and older, HT non-users, were randomly assigned to one of two groups: either two capsules of 80 mg red clover isoflavones daily for a 90-day period or placebo. After a 7-day washout period, medication was crossed-over for another 90 days. Total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein A (LpA) levels were assessed at baseline, 90 and 180 days. Women were divided into two groups: those with increased BMI (>or=25 kg/m(2)) and those with BMI < 25 kg/m(2). Red clover isoflavone supplementation had a positive effect on the lipid profile of women with increased BMI, evidenced by a significant decrease in TC, LDL-C and LpA levels. Isoflavones derived from red clover are an attractive alternative therapeutic option for high-risk populations such as postmenopausal women with increased BMI and abnormal lipid profile.

What is the opinion of the medical establishment?
The field of hormone or herbal therapy during or after menopause is very complicated and there is no consensus within the medical community regarding the role of red clover or other options for long term therapy. The medical community seems to be shifting its viewpoint on hormone replacement. It appears that most traditional doctors now prefer using low doses of hormones for a brief period of time to treat menopausal symptoms, but prefer not to continue hormone replacement therapy indefinitely as in the past. There is no agreement in the medical community regarding the role of natural herbs as a treatment for menopause symptoms.

Review of red clover benefit
It is difficult to know for sure what role red clover plays in the treatment of menopausal symptoms. It appears that red clover has a weak effect and certainly not as noticeable as estrogen therapy. But, red clover does not have the major safety concerns of estrogen and some women may find red clover extract supplement use to be of benefit.

You can find red clover as a tea, red clover whole herb, and red clover extract. Red clover is also found combined with black cohosh and other herbs in many herbal formulas for menopause. Herbal ingredient suppliers sell various red clover extract concentrations including red clover 2.5 percent isoflavones and 8 percent isoflavones;
Extract 8% /1% Isoflavone / Biochanin A and B.

Red clover supplements are used to treat symptoms of menopause because of their high content of the mildly estrogenic isoflavones which are daidzein, genistein, formononetin, and biochanin A.

Mechanism of action, how it works
Red clover extract acts on the mu-opiate receptor and the delta-opiate receptor. Therefore, red clover extracts act at the level of opiate receptors. Given the essential role of the opioid system in regulating temperature, mood, and hormonal levels and actions, this may explain in part the beneficial effect of red clover in reducing menopausal symptoms. There are other ways that red clover extracts act in the human body and further research will offer more explanations.

Research studies
Molecules. January 2014. Trifolium pratense as a Potential Natural Antioxidant.

The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: A randomized, double-blind, placebo-controlled study.
Gynecology Endocrinol. 2005. Foundation for Health and Well Being in the Climacteric 'FUCLIM', Guayaquil, Ecuador.
The unexpected results of the Women's Health Initiative study have decreased the use of conventional hormone therapy, changing physicians' and patients' attitudes towards hormone therapy and increasing their interest in alternative options. The present study aimed to evaluate the effect of isoflavones contained in red clover extracts (Trifolium pratense) on menopausal symptoms, lipids and vaginal cytology in menopausal women. Sixty postmenopausal women aged &gt;40 years, non-users of hormone therapy, with Kupperman index score 15, were double-blindly randomized to receive either a commercially available red clover isoflavone supplement (80 mg/day) or placebo for 90 days. Subsequently, after a 7-day washout period, subjects switched to receive the opposite treatment for a further 90 days. Results. There was no significant effect on body mass index, weight or blood pressure after either treatment phase. Red clover isoflavone supplementation significantly decreased the rate of menopausal symptoms and had a positive effect on vaginal cytology as expressed by improvement in karyopyknotic cornification and basal cell maturation indices. Mean total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels also decreased; however, only the latter was significantly lower compared with placebo. Compared with placebo, red clover isoflavone supplementation in postmenopausal women significantly decreased menopausal symptoms and had a positive effect on vaginal cytology and triglyceride levels.

Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense).
J Agric Food Chem. 2005. Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, University of Illinois, Chicago, Illinois
Because the prevailing form of hormone replacement therapy is associated with the development of cancer in breast and endometrial tissues, alternatives are needed for the management of menopausal symptoms. Formulations of Trifolium pratense L. (red clover) are being used to alleviate menopause-associated hot flashes but have shown mixed results in clinical trials. The strobiles of Humulus lupulusL. (hops) have been reported to contain the prenylflavanone, 8-prenylnaringenin (8-PN), as the most estrogenic constituent. Extracts of hops and red clover and their individual constituents including 8-PN, 6-prenylnaringenin (6-PN), isoxanthohumol (IX), and xanthohumol (XN) from hops and daidzein, formononetin, biochanin A, and genistein from red clover were compared using a variety of in vitro estrogenic assays. On the basis of these data, hops and red clover could be attractive for the development as herbal dietary supplements to alleviate menopause-associated symptoms.

Phytoestrogens derived from red clover: An alternative to estrogen replacement therapy?
J Steroid Biochem Mol Biol. 2005.
The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERbeta compared to ERalpha has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-kappaB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system. Currently 40-50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily dose. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet.

Modest protective effects of isoflavones from a red clover -derived dietary supplement on cardiovascular disease risk factors in perimenopausal women.
J Nutr. 2004.
Data suggest that soy protein, a source of isoflavones, may have favorable effects on cardiovascular risk factors. Women, ages 49-65 y, were randomized into this double blind, placebo-controlled trial of 43 mg red clover-derived isoflavones/d. A total of 177 women completed the trial. There were no differences between treatments for changes from baseline to 12 mo in total cholesterol, LDL cholesterol, triglycerides, HDL cholesterol, systolic and diastolic blood pressures, fibrinogen, and plasminogen activator inhibitor type 1 (PAI-1). Interactions between treatment and menopausal status were significant for changes in triglycerides and PAI-1, and changes were significant among perimenopausal women. Although there were potentially beneficial changes in triglycerides and PAI-1 among perimenopausal women consuming red clover isoflavones, this study suggests that isoflavones alone are not responsible for the well-documented effects of soy protein on blood lipids.

Effect of red clover isoflavones on cox-2 activity in murine and human monocyte/macrophage cells.
Nutr Cancer. 2004.
Long-term use of nonsteroidal anti-inflammatory drugs is associated with a reduction in the incidence of a range of cancers, the mechanism of which is thought to be cyclooxygenase (COX) inhibition. Because long-term ingestion of foods rich in isoflavones, such as legumes (beans, peas, lentils) has been associated with reduced cancer incidence, it was considered useful to examine the COX-inhibitory activities of individual isoflavones. Red clover dietary supplements also contain varying ratios of the 4 isoflavones commonly found in legume-based diets, namely, daidzein, genistein, formononetin, and biochanin. Thus, it is possible that the lower rates of some cancers in populations with a high intake of dietary isoflavones is linked to their inhibition of COX activity.

The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women.
Climacteric. 2004.
To examine the effects of dietary isoflavone supplementation with an extract from red clover on cognitive function in postmenopausal women. Thirty postmenopausal women aged greater than 60 years received either two tablets of an extract of aglycone isoflavones from red clover (each containing formononetin 25 mg, biochanin 2.5 mg and less than 1 mg of daidzein and genistein) for 6 months in a randomized, controlled clinical trial. Cognitive function tests were performed at baseline and at the end of isoflavone or placebo therapy. Isoflavone supplementation was associated with an apparent improvement in block design (a test of visual-spatial intelligence) compared to placebo (isoflavone +12%, placebo -3%), no improvement in verbal memory compared to an improvement on placebo (isoflavone +1%, placebo +29%) and a deterioration in digit recall compared to placebo (isoflavone -6%, placebo +12%). However, these findings were not statistically significant when corrections were made for potential chance findings due to multiple comparisons. Isoflavone supplementation does not appear to have major short-term effects on cognitive function in postmenopausal women. However, further clinical trials are required to determine whether small effects or long-term effects on cognitive function occur during isoflavone supplementation.

The effects of red clover isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial.
Am J Clin Nutr. 2004.
Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy (HRT). HRT has a beneficial effect on bone, but few trials in humans have investigated the effects of isoflavones on bone. The objective of the study was to determine the effect on bone density of a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A, 16 mg formononetin, 1 mg genistein, and 0.5 mg daidzein for 1 y. Effects on biochemical markers of bone turnover and body composition were also studied. Women aged 49-65 y  were enrolled in a double-blind, randomized, placebo-controlled trial; 177 completed the trial. Bone density, body composition, bone turnover markers, and diet were measured at baseline and after 12 mo. Loss of lumbar spine bone mineral content and bone mineral density was significantly lower in the women taking the red clover isoflavone supplement than in those taking the placebo. There were no significant treatment effects on hip bone mineral content or bone mineral density, markers of bone resorption, or body composition, but bone formation markers were significantly increased in the red clover group compared with placebo in postmenopausal women. These data suggest that, through attenuation of bone loss, red clover isoflavones have a potentially protective effect on the lumbar spine in women.

Red clover derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial.
Atkinson C, Warren RM, Sala E et al. Breast Cancer Res. 2004.
Isoflavones are hypothesized to protect against breast cancer, but it is not clear whether they act as estrogens or anti-estrogens in breast tissue. Our aim was to determine the effects of taking a red clover derived isoflavone supplement daily for 1 year on mammographic breast density. Effects on estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), lymphocyte tyrosine kinase activity and menopausal symptoms were also assessed. A total of 205 women (age range 49-65 years) with Wolfe P2 or DY mammographic breast patterns were randomly assigned to receive either a red clover derived isoflavone tablet (26 mg biochanin A, 16 mg formononetin, 1 mg genistein and 0.5 mg daidzein) or placebo. In contrast to studies showing that conventional hormone replacement therapies increase mammographic breast density, the red clover isoflavone supplement did not increase mammographic breast density in this population of women. Furthermore, there were no effects on estradiol, gonadotrophins, lymphocyte tyrosine kinase activity, or menopausal symptoms.

Red Clover Trifolium pratense Monograph: A Clinical Decision Support Tool.
J Herb Pharmcotherapy. 2003.
Red clover, a legume resembling soy is used by man as a phytoestrogen. Other uses include asthma, pertussis, cancer and gout. The authors systematically review red clover in terms of pharmacology, efficacy, safety, side effects, standardization, dosing, toxicology as well as other parameters.

Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes.
Department of Clinical Pharmacology, St. George Hospital UNSW, Kogarah, NSW, Australia.
The aim of this study was to determine whether dietary supplementation with isoflavones from red clover affected ambulatory blood pressure and forearm vascular endothelial function in postmenopausal type 2 diabetic women.  Sixteen postmenopausal type 2 diabetics treated with diet or oral hypoglycaemic therapy completed a randomized double-blind crossover trial of dietary supplementation with isoflavones from red clover (approximately 50 mg/day) for 4 weeks compared to placebo. Twenty-four-hour ambulatory blood pressure recordings and forearm vascular responses to acetylcholine, nitroprusside and L-nitromonomethylarginine (L-NMMA) were measured at the end of each treatment period. Mean daytime systolic and diastolic blood pressures were significantly lower during isoflavone therapy compared to placebo. The increase in forearm vascular resistance following L-NMMA was significantly greater during isoflavone supplementation, suggesting an improvement in basal endothelial function. Plasma lipoproteins, glycated haemoglobin and forearm vascular responses to acetylcholine and nitroprusside did not differ significantly between isoflavone and placebo therapy. Isoflavone supplementation from red clover may favorably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.
Red clover herb Red clover blossom.

Red Clover Products
Natrol, Inc. has licensed the U.S. rights to the Promensil and Trinovin brands from Novogen Limited, an Australian-based biotechnology company.
The Promensil and Trinovin brands are dietary supplements based on red clover isoflavones that are designed to meet specific health needs of aging adults. Christopher Naughton, CEO of Novogen, said, "Novogen is extremely pleased to have secured Natrol as its exclusive licensee for Promensil and Trinovin in the U.S. Natrol brings marketing expertise and the product critical mass that will enable the premium brands Promensil and Trinovin to be elevated to their potential in the U.S. marketplace." Promensil is a dietary supplement tested for menopausal symptoms, including hot flashes and night sweatsh. Promensil currently is distributed through mass and super center, chain drug and grocery stores, the health food channel, and direct sale over the Internet. Promensil is sold globally in 12 countries, including the U.S. Trinovin, which was first sold in the U.S. in 1999, helps maintain prostate and urinary health. Trinovin currently is distributed through the health food channel and direct sale over the Internet.

Red Clover Tea
Several companies make red clover tea. These include Alvita red clover tea, Botanic Choice red clover tea, Celebration Herbals red clover tea , and TerraVita red clover tea and blossom. If you purchase tea, it is preferable to have each tea bag individually sealed to prevent evaporation of volatile oils and to prevent oxidation of the herb. The benefit of red clover tea is difficult to compare to red clover extract since it is difficult to know how much of the isoflavones from the red clover tea bag seep into the hot water.

Traditional use
Red clover has been used traditionally as a medicinal agent by Asian, European, and Native American cultures as an expectorant in asthma, and as an alterative (blood purifier) to treat psoriasis, eczema, and other chronic skin conditions.

Red Clover extract does seem to be helping my hot flashes go away. However within 3-4 hours of taking the first red clover dose of the day, I have a bad taste in my mouth and my food doesn't taste right. If I take it at dinner also the same is true. The effect is gone by breakfast the next day and breakfast tastes normal. Then by mid morning I have the bad taste back. I didn't see this listed as a red clover side effect anywhere.
   This is the first time anyone has mentioned to us about this potential red clover side effect.

I Just been reading the paper you wrote on Red Clover and feel from your studies its safe, I used it for 8months last year with 100% success for hot flashes before I used it were 10 or more daily and 4 or 5 night sweats, after 3 weeks on red clover I was cured but have been told I cant stay on it because of not enough testing done past 12 months. Could you please tell me your opinion on 1 tablet a day 80mg isoflavone for longer term, I used the Promensil brand but have seen other . For 2 months I am off it but in hot flash night sweat hell and going to buy more red clover today as I want to use natural herbs not HRT patches.
   A. In my opinion red clover and other herbs are safer than estrogen and hormones, although for most people they do not work as well.

Buy Red Clover stem, leaf, flower, Nature's Way, 100 Capsules, 400 mg each pill
Certified Organically Grown Red Clover Herb
In Europe, red clover herb (Trifolium pratense) is widely cultivated and used as a salad herb and as a tonic. The globular heads of reddish-purple flowers have long been prized by herbalists. This red clover herb supplement contains only full clover blossoms and their accompanying leaves.

Buy Red Clover Supplement

Supplement Facts
Amount Per capsule
Red Clover herb 400 mg
   (stem, leaf, flower)

As an addition to the daily diet, take 1 or 2 red clover capsules 1 to 3 times daily.