Red Clover Extract

Last Updated: September 21, 2023

Red clover (Trifolium pratense) is a plant in the Fabaceae (legume) family that is a source of isoflavones with estrogen-like effects, similar to soy. Red clover has primarily been researched as a supplement in menopause and might reduce the frequency of hot flashes, but other menopause-related outcomes have been largely inconclusive.

Red Clover Extract is most often used for

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 else is Red Clover Extract known as?
Note that Red Clover Extract is also known as:
  • 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]

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Update History
2023-09-21 00:30:02

More meta-analyses added

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We didn't upload all the meta-analyses to this page last week due to an error. They have now been added!

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2023-09-14 17:02:58

Standard FAQ and database update

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We searched for new studies on red clover extract, analyzed them, and added their information to our FAQs and database.

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References
  1. ^Kanadys W, Barańska A, Błaszczuk A, Polz-Dacewicz M, Drop B, Kanecki K, Malm MEvaluation of Clinical Meaningfulness of Red Clover ( L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Nutrients.(2021-Apr-11)
  2. ^Shahmohammadi A, Ramezanpour N, Mahdavi Siuki M, Dizavandi F, Ghazanfarpour M, Rahmani Y, Tahajjodi R, Babakhanian MThe efficacy of herbal medicines on anxiety and depression in peri- and postmenopausal women: A systematic review and meta-analysis.Post Reprod Health.(2019-Sep)
  3. ^Kazlauskaite JA, Ivanauskas L, Marksa M, Bernatoniene JThe Effect of Traditional and Cyclodextrin-Assisted Extraction Methods on L. (Red Clover) Extracts Antioxidant Potential.Antioxidants (Basel).(2022-Feb-21)
  4. ^Bolego C, Poli A, Cignarella A, Paoletti RPhytoestrogens: pharmacological and therapeutic perspectives.Curr Drug Targets.(2003-Jan)
  5. ^Piersen CE, Booth NL, Sun Y, Liang W, Burdette JE, van Breemen RB, Geller SE, Gu C, Banuvar S, Shulman LP, Bolton JL, Farnsworth NRChemical and biological characterization and clinical evaluation of botanical dietary supplements: a phase I red clover extract as a model.Curr Med Chem.(2004-Jun)
  6. ^Myers SP, Vigar VEffects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis.Phytomedicine.(2017-Jan-15)
  7. ^Luís Â, Domingues F, Pereira LEffects of red clover on perimenopausal and postmenopausal women's blood lipid profile: A meta-analysis.Climacteric.(2018-Oct)
  8. ^Kolodziejczyk-Czepas JTrifolium species - the latest findings on chemical profile, ethnomedicinal use and pharmacological properties.J Pharm Pharmacol.(2016-Jul)
  9. ^Krenn L, Unterrieder I, Ruprechter RQuantification of isoflavones in red clover by high-performance liquid chromatography.J Chromatogr B Analyt Technol Biomed Life Sci.(2002-Sep-25)
  10. ^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)
  11. ^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)
  12. ^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)
  13. ^Zhang H, Zhao J, Shang H, Guo Y, Chen SExtraction, purification, hypoglycemic and antioxidant activities of red clover (Trifolium pratense L.) polysaccharides.Int J Biol Macromol.(2020-Apr-01)
  14. ^Khorasani Esmaeili A, Mat Taha R, Mohajer S, Banisalam BAntioxidant Activity and Total Phenolic and Flavonoid Content of Various Solvent Extracts from In Vivo and In Vitro Grown Trifolium pratense L. (Red Clover).Biomed Res Int.(2015)
  15. ^Hanganu, A., et al.POLYPHENOLIC PROFILE AND ANTIOXIDANT AND ANTIBACTERIAL ACTIVITIES FROM TWO TRIFOLIUM SPECIESFarmacia.(2017 Jun)
  16. ^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)
  17. ^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)
  18. ^Chen MN, Lin CC, Liu CFEfficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic reviewClimacteric.(2015 Apr)
  19. ^Védrine N, Mathey J, Morand C, Brandolini M, Davicco MJ, Guy L, Rémésy C, Coxam V, Manach COne-month exposure to soy isoflavones did not induce the ability to produce equol in postmenopausal women.Eur J Clin Nutr.(2006-Sep)
  20. ^Escande A, Pillon A, Servant N, Cravedi JP, Larrea F, Muhn P, Nicolas JC, Cavaillès V, Balaguer PEvaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta.Biochem Pharmacol.(2006-May-14)
  21. ^Jiang Y, Gong P, Madak-Erdogan Z, Martin T, Jeyakumar M, Carlson K, Khan I, Smillie TJ, Chittiboyina AG, Rotte SC, Helferich WG, Katzenellenbogen JA, Katzenellenbogen BSMechanisms enforcing the estrogen receptor β selectivity of botanical estrogensFASEB J.(2013 Nov)
  22. ^Sabudak T, Guler NTrifolium L.--a review on its phytochemical and pharmacological profile.Phytother Res.(2009-Mar)
  23. ^Kolodziejczyk-Czepas J, Nowak P, Moniuszko-Szajwaj B, Kowalska I, Stochmal AFree radical scavenging actions of three Trifolium species in the protection of blood plasma antioxidant capacity in vitro.Pharm Biol.(2015)
  24. ^Okochi M, Kenjo A, Asai E, Ueda K, Gotoh MTwo-step hepatic artery reconstruction for a hepatic artery lacking in length for the use of a microclamp in living donor liver transplantation.Int J Surg Case Rep.(2016)
  25. ^Katharine E Reed, Juliana Camargo, Jill Hamilton-Reeves, Mindy Kurzer, Mark MessinaNeither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studiesReprod Toxicol.(2021 Mar)
  26. ^Song D, He H, Indukuri R, Huang Z, Stepanauskaite L, Sinha I, Haldosén LA, Zhao C, Williams CERα and ERβ Homodimers in the Same Cellular Context Regulate Distinct Transcriptomes and Functions.Front Endocrinol (Lausanne).(2022)
  27. ^Atkinson C, Warren RM, Sala E, Dowsett M, Dunning AM, Healey CS, Runswick S, Day NE, Bingham SARed-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial ISRCTN42940165Breast Cancer Res.(2004)
  28. ^Fritz H, Seely D, Flower G, Skidmore B, Fernandes R, Vadeboncoeur S, Kennedy D, Cooley K, Wong R, Sagar S, Sabri E, Fergusson DSoy, red clover, and isoflavones and breast cancer: a systematic review.PLoS One.(2013)
  29. ^Hooper L, Madhavan G, Tice JA, Leinster SJ, Cassidy AEffects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trialsHum Reprod Update.(2010 Nov-Dec)
Examine Database References
  1. IGF-1 - Vrieling A, Rookus MA, Kampman E, Bonfrer JM, Bosma A, Cats A, van Doorn J, Korse CM, Witteman BJ, van Leeuwen FE, van't Veer LJ, Voskuil DWNo effect of red clover-derived isoflavone intervention on the insulin-like growth factor system in women at increased risk of colorectal cancerCancer Epidemiol Biomarkers Prev.(2008 Oct)
  2. IGF-1 - Vrieling A, Rookus MA, Kampman E, Bonfrer JM, Korse CM, van Doorn J, Lampe JW, Cats A, Witteman BJ, van Leeuwen FE, van't Veer LJ, Voskuil DWIsolated isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer riskJ Nutr.(2007 Feb)
  3. Menopausal Symptoms - Atkinson C, Warren RM, Sala E, Dowsett M, Dunning AM, Healey CS, Runswick S, Day NE, Bingham SARed-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial ISRCTN42940165Breast Cancer Res.(2004)
  4. Plasminogen Inhibitor-1 - Atkinson C, Oosthuizen W, Scollen S, Loktionov A, Day NE, Bingham SAModest 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 womenJ Nutr.(2004 Jul)
  5. High-density lipoprotein (HDL) - Blakesmith SJ, Lyons-Wall PM, George C, Joannou GE, Petocz P, Samman SEffects of supplementation with purified red clover (Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal womenBr J Nutr.(2003 Apr)
  6. High-density lipoprotein (HDL) - Campbell MJ, Woodside JV, Honour JW, Morton MS, Leathem AJEffect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot studyEur J Clin Nutr.(2004 Jan)
  7. High-density lipoprotein (HDL) - Howes JB, Tran D, Brillante D, Howes LGEffects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetesDiabetes Obes Metab.(2003 Sep)
  8. High-density lipoprotein (HDL) - Nestel PJ, Pomeroy S, Kay S, Komesaroff P, Behrsing J, Cameron JD, West LIsoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal womenJ Clin Endocrinol Metab.(1999 Mar)
  9. Blood Pressure - Teede HJ, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJIsoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal womenArterioscler Thromb Vasc Biol.(2003 Jun 1)
  10. Total cholesterol - 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)
  11. Homocysteine - Samman S, Koh HS, Flood VM, Blakesmith SJ, Petocz P, Lyons-Wall PMRed clover (Trifolium pratense) isoflavones and serum homocysteine in premenopausal women: a pilot studyJ Womens Health (Larchmt).(2009 Nov)
  12. Testosterone - Lee CC, Bloem CJ, Kasa-Vubu JZ, Liang LJEffect of oral phytoestrogen on androgenicity and insulin sensitivity in postmenopausal womenDiabetes Obes Metab.(2012 Apr)
  13. Memory - Howes JB, Bray K, Lorenz L, Smerdely P, Howes LGThe effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal womenClimacteric.(2004 Mar)
  14. Skin Quality - Lipovac M, Chedraui P, Gruenhut C, Gocan A, Kurz C, Neuber B, Imhof MEffect of Red Clover Isoflavones over Skin, Appendages, and Mucosal Status in Postmenopausal WomenObstet Gynecol Int.(2011)
  15. Weight - Howes JB, Sullivan D, Lai N, Nestel P, Pomeroy S, West L, Eden JA, Howes LGThe effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemiaAtherosclerosis.(2000 Sep)
  16. Weight - Baber RJ, Templeman C, Morton T, Kelly GE, West LRandomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in womenClimacteric.(1999 Jun)
  17. Weight - Hidalgo LA, Chedraui PA, Morocho N, Ross S, San Miguel GThe effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled studyGynecol Endocrinol.(2005 Nov)
  18. Weight - Terzic MM, Dotlic J, Maricic S, Mihailovic T, Tosic-Race BInfluence of red clover-derived isoflavones on serum lipid profile in postmenopausal womenJ Obstet Gynaecol Res.(2009 Dec)
  19. Testosterone - Imhof M, Gocan A, Reithmayr F, Lipovac M, Schimitzek C, Chedraui P, Huber JEffects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal womenMaturitas.(2006 Aug 20)
  20. Sex Hormone Binding Globulin - Knight DC, Howes JB, Eden JAThe effect of Promensil, an isoflavone extract, on menopausal symptomsClimacteric.(1999 Jun)
  21. Menopausal Symptoms - Lipovac M, Chedraui P, Gruenhut C, Gocan A, Kurz C, Neuber B, Imhof MThe effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal womenGynecol Endocrinol.(2012 Mar)
  22. Menopausal Symptoms - del Giorno C, Fonseca AM, Bagnoli VR, Assis JS, Soares JM Jr, Baracat ECEffects of Trifolium pratense on the climacteric and sexual symptoms in postmenopause womenRev Assoc Med Bras.(2010 Sep-Oct)
  23. Menopausal Symptoms - van de Weijer PH, Barentsen RIsoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placeboMaturitas.(2002 Jul 25)
  24. Menopausal Symptoms - Ehsanpour S, Salehi K, Zolfaghari B, Bakhtiari SThe effects of red clover on quality of life in post-menopausal womenIran J Nurs Midwifery Res.(2012 Jan)
  25. Total cholesterol - Schult TM, Ensrud KE, Blackwell T, Ettinger B, Wallace R, Tice JAEffect of isoflavones on lipids and bone turnover markers in menopausal womenMaturitas.(2004 Jul 15)
  26. Total cholesterol - 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)
  27. Anxiety Symptoms - Geller SE, Shulman LP, van Breemen RB, Banuvar S, Zhou Y, Epstein G, Hedayat S, Nikolic D, Krause EC, Piersen CE, Bolton JL, Pauli GF, Farnsworth NRSafety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trialMenopause.(2009 Nov-Dec)
  28. Anxiety Symptoms - Lipovac M, Chedraui P, Gruenhut C, Gocan A, Stammler M, Imhof MImprovement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extractsMaturitas.(2010 Mar)
  29. Hot Flash Symptoms - Tice JA, Ettinger B, Ensrud K, Wallace R, Blackwell T, Cummings SRPhytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trialJAMA.(2003 Jul 9)
  30. Hot Flash Symptoms - Myers SP, Vigar VEffects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis.Phytomedicine.(2017-Jan-15)
  31. Hot Flash Symptoms - Kanadys W, Barańska A, Błaszczuk A, Polz-Dacewicz M, Drop B, Kanecki K, Malm MEvaluation of Clinical Meaningfulness of Red Clover ( L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Nutrients.(2021-Apr-11)
  32. High-density lipoprotein (HDL) - Chedraui P, San Miguel G, Hidalgo L, Morocho N, Ross SEffect of Trifolium pratense-derived isoflavones on the lipid profile of postmenopausal women with increased body mass indexGynecol Endocrinol.(2008 Nov)
  33. High-density lipoprotein (HDL) - Nestel P, Cehun M, Chronopoulos A, DaSilva L, Teede H, McGrath BA biochanin-enriched isoflavone from red clover lowers LDL cholesterol in menEur J Clin Nutr.(2004 Mar)
  34. Weight - Atkinson C, Compston JE, Day NE, Dowsett M, Bingham SAThe effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trialAm J Clin Nutr.(2004 Feb)
  35. Bone Mineral Density - Clifton-Bligh PB, Baber RJ, Fulcher GR, Nery ML, Moreton TThe effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolismMenopause.(2001 Jul-Aug)
  36. Testosterone - Katharine E Reed, Juliana Camargo, Jill Hamilton-Reeves, Mindy Kurzer, Mark MessinaNeither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studiesReprod Toxicol.(2021 Mar)
  37. Sexual Function - Sha'ari N, Woon LS, Sidi H, Das S, Bousman CA, Mohamed Saini SBeneficial effects of natural products on female sexual dysfunction: A systematic review and meta-analysis.Phytomedicine.(2021-Dec)