What is red clover?
Red clover (Triofolium pratense) is a perennial plant in the legume family (Fabaceae). It grows in many regions of the world, including North America, Europe, Asia, and Africa.[7] The aerial (above-ground) parts of the red clover plant have been used as a traditional herbal medicine for a variety of ailments,[8] but the research on red clover has generally centered around menopause.
Red clover contains bioactive plant compounds called isoflavones which possess phytoestrogenic properties. While 16 different isoflavones have been identified in red clover, biochanin A and formononetin are thought to be the most abundant.[9] Interestingly, upon consumption, biochanin A and formononetin are metabolized into genistein and daidzein (the same isoflavones found in soy), respectively, which are the dominant isoflavones found in the blood during red clover supplementation.[1][10]
What are red clover’s main benefits?
Red clover may be a beneficial supplement in menopause when used to reduce hot flashes. A 2021 meta-analysis of randomized controlled trials found that red clover supplementation taken for 3 months resulted in an average of 1.7 fewer hot flashes daily compared to placebo, particularly in postmenopausal women experiencing at least 5 hot flashes daily.[1] However, these effects were not sustained in trials performing a 12-month follow-up, and over half of the trials were at least partially funded by the red clover manufacturer, which could bias these results. Red clover might slightly reduce total cholesterol and raise high-density lipoprotein (HDL) in postmenopausal women with no other health conditions, but the effects are so small they likely would not influence overall cardiovascular health.[11] Research looking at other menopause-related outcomes like vaginal health, sleep behavior, mood, and bone health have had mixed results and are currently inconclusive.[12]
Preclinical research suggests that red clover may possess antioxidant, antimicrobial, and hypoglycemic (blood-sugar-reducing) properties,[13][14][15] but establishing the clinical relevance of these effects will require further research.
What are red clover’s main drawbacks?
Red clover supplementation seems to be quite safe when used for up to 3 years.[16][17] Most trials have not found significant side effects compared to placebo,[18][13] although larger clinical trials are needed to properly evaluate side effect risk.
The concentration and type of active compounds in red clover can vary depending on how the plant was grown and processed, which can impact its effects on the body.[3][5] This can result in inconsistent effects when using different extracts of red clover. Variability in effect may also be seen between people due to differences in genetics and the gut microbiome, both of which can impact how isoflavones are metabolized in the body.[19]
How does red clover work?
The estrogen-like effects of red clover are due to its contents of isoflavones (biochanin A, formononetin, genistein, and daidzein), which are all considered phytoestrogens. Because of their structural similarity to estrogen, these isoflavones can bind to estrogen receptors in the body which may help reduce some of the symptoms of menopause that occur due to estrogen deficiency. There are two subtypes of estrogen receptors, estrogen receptor beta (ERβ) and estrogen receptor alpha (ERα), which are distributed differently throughout body tissues and have different actions. While estrogen binds both receptors equally, red clover isoflavones have a particular affinity for estrogen receptor β (ERβ) and only a weak affinity for estrogen receptor α (ERα), which means that the estrogenic effects of isoflavones will differ slightly from estrogen.[20][21]
Red clover also contains many other bioactive compounds, including the polyphenols coumaric acid, ferulic acid, and quercetin. While these contribute to the antioxidant and antimicrobial effects of red clover in vitro, it’s unclear what effects they might have when red clover is used as a supplement.[15]
What are other names for Red Clover Extract
- trifolium pratense
- biochanin A
- Formononetin Promensil (brand name)
- Menoflavon (brand name)
Dosage information
Red clover is usually dosed based on total isoflavone content, with 40–80 mg of isoflavones orally daily being the most commonly used dosing. Some research suggests that dosages of 80 mg daily may be more effective,[1][2] but further research is needed to validate this. Red clover can also be applied directly to the skin, but few studies have utilized this route.
Due to the nature of herbal medicines, different growing environments and extraction methods will lead to variations in both the concentration and relative abundances of the different isoflavones in red clover which can impact the effects it has on the body.[3][4][5] Therefore, the effects produced from a particular red clover formulation may not be seen with a different formulation. Accordingly, if a study fails to specify the isoflavone composition of the formulation used, it can be challenging to replicate its findings.
Some commercially made red clover extracts are available that contain standardized amounts of red clover isoflavones. The most-studied product is Promensil, which is considered equivalent to another standardized extract, Menoflavon. Both contain roughly 50% biochanin A, 35% formononetin, 3% genistein, and 1% daidzein.[6]
Frequently asked questions
Red clover (Triofolium pratense) is a perennial plant in the legume family (Fabaceae). It grows in many regions of the world, including North America, Europe, Asia, and Africa.[7] The aerial (above-ground) parts of the red clover plant have been used as a traditional herbal medicine for a variety of ailments,[8] but the research on red clover has generally centered around menopause.
Red clover contains bioactive plant compounds called isoflavones which possess phytoestrogenic properties. While 16 different isoflavones have been identified in red clover, biochanin A and formononetin are thought to be the most abundant.[9] Interestingly, upon consumption, biochanin A and formononetin are metabolized into genistein and daidzein (the same isoflavones found in soy), respectively, which are the dominant isoflavones found in the blood during red clover supplementation.[1][10]
Red clover has been cultivated for thousands of years both as a traditional medicine and a food source by Asian, European, and Indigenous North American cultures.[8] Medicinally, red clover has been used for a wide variety of ailments, including skin problems, illnesses affecting the lungs (e.g., pneumonia, bronchitis, asthma), disorders of the nervous and reproductive systems, heart disease, sore throat, burns, fever, and as a general analgesic and antiseptic.[8][22][23]
Interestingly, scientific research on clover species was sparked in the 1940s when it was observed that sheep grazing in pastures with a particular type of clover (subterranean clover, Trifolium subterraneum) became infertile.[8] This led to the initial observations of the estrogenic properties of clover species.[24]
Red clover may be a beneficial supplement in menopause when used to reduce hot flashes. A 2021 meta-analysis of randomized controlled trials found that red clover supplementation taken for 3 months resulted in an average of 1.7 fewer hot flashes daily compared to placebo, particularly in postmenopausal women experiencing at least 5 hot flashes daily.[1] However, these effects were not sustained in trials performing a 12-month follow-up, and over half of the trials were at least partially funded by the red clover manufacturer, which could bias these results. Red clover might slightly reduce total cholesterol and raise high-density lipoprotein (HDL) in postmenopausal women with no other health conditions, but the effects are so small they likely would not influence overall cardiovascular health.[11] Research looking at other menopause-related outcomes like vaginal health, sleep behavior, mood, and bone health have had mixed results and are currently inconclusive.[12]
Preclinical research suggests that red clover may possess antioxidant, antimicrobial, and hypoglycemic (blood-sugar-reducing) properties,[13][14][15] but establishing the clinical relevance of these effects will require further research.
Red clover supplementation seems to be quite safe when used for up to 3 years.[16][17] Most trials have not found significant side effects compared to placebo,[18][13] although larger clinical trials are needed to properly evaluate side effect risk.
The concentration and type of active compounds in red clover can vary depending on how the plant was grown and processed, which can impact its effects on the body.[3][5] This can result in inconsistent effects when using different extracts of red clover. Variability in effect may also be seen between people due to differences in genetics and the gut microbiome, both of which can impact how isoflavones are metabolized in the body.[19]
Given the estrogen-like effects of red clover isoflavones, concerns have been raised regarding the potential feminization of men following supplementation. However, this is not supported by current evidence. Supplementation with isoflavones (from soy or red clover) for up to 1 year has not been found to affect hormone levels in men, including testosterone, estrogen, or sex hormone binding globulin.[25]
While red clover is sometimes supplemented in men for prostate health, there is currently no convincing evidence to support this use.
Certain types of breast cancers are considered estrogen-dependent, meaning that estrogen (via the estrogen receptor subtype ERα) actually causes the tumor to develop and grow. Given the estrogen-like properties of red clover isoflavones, it is important to establish whether supplementation could impact the risk of these cancers. While ERα can stimulate tumor growth, in vitro research suggests that ERβ may actually have the opposite function of suppressing tumor growth.[26] Red clover isoflavones preferentially bind to ERβ receptors, which could be beneficial in terms of cancer risk, but they can still bind to ERα receptors, particularly when present at higher concentrations.[21]
In women considered to be at a high risk of breast cancer due to family history or breast density patterns, supplementation with red clover for 1 to 3 years did not cause any changes in a marker of breast cancer (breast tissue density),[17][27] although this marker is not considered to be a highly accurate predictor of cancer risk.[28] When looking at isoflavones from soy or red clover, a 2010 meta-analysis found that isoflavones had no effect on breast density in postmenopausal women but slightly increased breast density in premenopausal women, although there were too few cases of breast cancer in the sample to assess the impact of isoflavones on breast cancer rates.[29] Given the rare occurrence of breast cancer, trials with larger sample sizes would be required to more accurately define the relationship between red clover isoflavones and breast cancer risk.
The estrogen-like effects of red clover are due to its contents of isoflavones (biochanin A, formononetin, genistein, and daidzein), which are all considered phytoestrogens. Because of their structural similarity to estrogen, these isoflavones can bind to estrogen receptors in the body which may help reduce some of the symptoms of menopause that occur due to estrogen deficiency. There are two subtypes of estrogen receptors, estrogen receptor beta (ERβ) and estrogen receptor alpha (ERα), which are distributed differently throughout body tissues and have different actions. While estrogen binds both receptors equally, red clover isoflavones have a particular affinity for estrogen receptor β (ERβ) and only a weak affinity for estrogen receptor α (ERα), which means that the estrogenic effects of isoflavones will differ slightly from estrogen.[20][21]
Red clover also contains many other bioactive compounds, including the polyphenols coumaric acid, ferulic acid, and quercetin. While these contribute to the antioxidant and antimicrobial effects of red clover in vitro, it’s unclear what effects they might have when red clover is used as a supplement.[15]
Update History
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Research Breakdown
References
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- ^Howes J, Waring M, Huang L, Howes LGLong-term pharmacokinetics of an extract of isoflavones from red clover (Trifolium pratense).J Altern Complement Med.(2002-Apr)
- ^Błaszczuk A, Barańska A, Kanadys W, Malm M, Jach ME, Religioni U, Wróbel R, Herda J, Polz-Dacewicz MRole of Phytoestrogen-Rich Bioactive Substances ( L., L., L.) in Cardiovascular Disease Prevention in Postmenopausal Women: A Systematic Review and Meta-Analysis.Nutrients.(2022-Jun-14)
- ^Ghazanfarpour M, Sadeghi R, Roudsari RL, Khorsand I, Khadivzadeh T, Muoio BRed clover for treatment of hot flashes and menopausal symptoms: A systematic review and meta-analysis.J Obstet Gynaecol.(2016)
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- ^Hanganu, A., et al.POLYPHENOLIC PROFILE AND ANTIOXIDANT AND ANTIBACTERIAL ACTIVITIES FROM TWO TRIFOLIUM SPECIESFarmacia.(2017 Jun)
- ^Clifton-Bligh PB, Nery ML, Clifton-Bligh RJ, Visvalingam S, Fulcher GR, Byth K, Baber RRed clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized, double-blind, placebo-controlled study.Eur J Clin Nutr.(2015-Jan)
- ^Powles TJ, Howell A, Evans DG, McCloskey EV, Ashley S, Greenhalgh R, Affen J, Flook LA, Tidy ARed clover isoflavones are safe and well tolerated in women with a family history of breast cancerMenopause Int.(2008 Mar)
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