Red Clover Extract

The part used of red clover is the flower top. Red clover contains isoflavones, a class of phytoestrogens which are structurally similar to estrogens, hence they are very useful for pre- and menopausal women. However, the beta estrogen receptor predominates in the heart, vasculature, bone and bladder, which may account for some of Red Clover's beneficial effects.

Red clover may help protect against heart disease in several ways. Red clover isoflavones have been associated with an increase in "good" high-density lipoprotein (HDL) cholesterol in pre- and postmenopausal women. One study found that menopausal women taking red clover supplements had more flexible and stronger arteries (called arterial compliance), which can help prevent heart disease.

Red clover may also have blood-thinning properties, which keeps blood clots from forming. It appears to improve blood flow.



Clinical Studies
Red Clover Extract


Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes

Howes JB, Tran D, Brillante D, Howes LG.
Department of Clinical Pharmacology, St. George Hospital UNSW, Kogarah, NSW, Australia.

OBJECTIVE: 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. DESIGN: 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. RESULTS: Mean daytime systolic and diastolic blood pressures were significantly lower during isoflavone therapy compared to placebo (-8.0 +/- 3.4 and -4.3 +/- 1.9 mmHg respectively, p < 0.05). The increase in forearm vascular resistance following L-NMMA was significantly greater during isoflavone supplementation (20.9 +/- 6.5) than placebo (3.7 +/- 2.9 arbitrary units, p < 0.05), 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. CONCLUSION: Isoflavone supplementation from red clover may favourably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.

Publication Types:
·    Clinical Trial
·    Randomized Controlled Trial

PMID: 12940870 [PubMed - indexed for MEDLINE]


The isoflavone metabolite cis-tetrahydrodaidzein inhibits ERK-1 activation and proliferation in human vascular smooth muscle cells

Ling S, Dai A, Williams MR, Husband AJ, Nestel PJ, Komesaroff PA, Sudhir K.
Hormones and the Vasculature Laboratory, Baker Medical Research Institute, Melbourne, Australia.

Phytoestrogens have recently been proposed as alternatives to estrogens for cardiovascular protection; however, the effect of their metabolites on vascular biology is unclear. We studied the effect of a red clover-derived isoflavone metabolite cis-tetrahydrodaidzein (cis-THD) on human vascular smooth muscle cell (VSMC) proliferation. Cis-THD significantly inhibited platelet-derived growth factor (PDGF) BB-induced DNA synthesis (10% at 1 nmol/L, 17% at 10, 100 nmol/L; 17beta-estradiol: 27% inhibition at 1, 10 nmol/L, 33% at 100 nmol/L). Cis-THD reduced PDGF BB-induced increase in cell numbers. Cis-THD showed high binding affinity to estrogen receptors (ER) by ER competitor assays; its inhibitory effect on DNA synthesis was abolished by the ER antagonist ICI 182780 (100 nmol/L), indicating ER-mediation. Immunoprecipitation assays revealed that cis-THD inhibited PDGF BB-stimulated activation of mitogen-activated protein (MAP) kinase ERK-1 by 34% at 1 nmol/L, 58% at 10 nmol/L, and 81% at 100 nmol/L, while MAP kinase JNK and p38 activities were unaltered. Thus, the isoflavone metabolite cis-THD inhibits PDGF-induced ERK-1 activation and cell proliferation in human VSMC, suggesting a potential beneficial effect in cardiovascular protection.

PMID: 15071348 [PubMed - indexed for MEDLINE]


Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes

Howes JB, Tran D, Brillante D, Howes LG.
Department of Clinical Pharmacology, St. George Hospital UNSW, Kogarah, NSW, Australia.

OBJECTIVE: 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. DESIGN: 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. RESULTS: Mean daytime systolic and diastolic blood pressures were significantly lower during isoflavone therapy compared to placebo (-8.0 +/- 3.4 and -4.3 +/- 1.9 mmHg respectively, p < 0.05). The increase in forearm vascular resistance following L-NMMA was significantly greater during isoflavone supplementation (20.9 +/- 6.5) than placebo (3.7 +/- 2.9 arbitrary units, p < 0.05), 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. CONCLUSION: Isoflavone supplementation from red clover may favourably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.

PMID: 12940870 [PubMed - indexed for MEDLINE


Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women

Teede HJ, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJ.
Vascular Research Group, Department of Medicine, Monash University, Clayton, Australia.

OBJECTIVE: This study was undertaken to address the vascular effects of isolated isoflavones as potential contributors to their cardioprotective properties, focusing on biochanin and formononetin. METHODS AND RESULTS: In a randomized, double-blind trial, 80 healthy subjects, 46 men and 34 women, 45 to 75 years of age, received isoflavones enriched in either biochanin or formononetin (precursors of genistein and daidzein; 80 mg/d) crossed over randomly with placebo in two 6-week periods. The end points were measured at baseline and after each intervention and included large artery stiffness (systemic arterial compliance and pulse wave velocity), endothelial function in conduit arteries (flow-mediated vasodilation), 24-hour ambulatory blood pressure, and total peripheral resistance. Isoflavone intervention significantly reduced arterial stiffness with improved systemic arterial compliance (P=0.04; repeated-measures ANOVA, Bonferroni correction) attributable to a reduction in total peripheral resistance (P=0.03) and a corresponding reduction in central pulse wave velocity (P=0.02) compared with placebo. Isoflavones did not affect blood pressure (P=0.5) or flow-mediated vasodilation (P=0.44). Improvements seemed limited to formononetin-enriched isoflavones (adjusted P=0.06). Formononetin treatment also reduced circulating vascular adhesion cell molecule-1 (P<0.01). CONCLUSIONS: In normotensive men and postmenopausal women, red clover isoflavones enriched in formononetin reduced arterial stiffness and total vascular resistance but had no effect on blood pressure. These effects may partly explain the lower cardiovascular risk in populations eating isoflavone-rich diets.

PMID: 12714433 [PubMed - indexed for MEDLINE]