Many researchers have proposed a link between the isoflavone-rich Asian diet and a lowered risk of menopausal problems in Japanese women, including reduced rates of cardiovascular disease. In one of the first published studies on a purified red clover extract (Trifolium pratense L., Fabaceae) scientists found that the supplement improved arterial compliance (a measure of elasticity of the large arteries) in postmenopausal women (Nestel et al., 1999). Declining arterial compliance during and after menopause is known to increase a woman's chance of developing heart disease later in life.
Researchers in Australia tested two different dosages of red clover extract against placebo in this randomized, double-blind, placebo-controlled study. After an initial three to four week run-in period and a five-week placebo period for all 17 participants, the women were divided into two treatment groups for an additional 10 weeks. During the first five weeks of active treatment, women took either one red clover tablet (40 mg isoflavones) and one placebo tablet daily, or two placebo tablets daily. During the final five weeks of the study, the dosage for the red clover group was increased to two red clover tablets (80 mg isoflavones) daily. The red clover extract (Promensil®, Novogen Ltd., North Ryde, Australia) was standardized to contain the following isoflavones: 4 mg genistein, 3.5 mg daidzein, 24.5 mg biochanin, and 8 mg formononetin.
At the beginning of the study, all women were free of obvious cardiovascular disease. Participants were required to discontinue the use of any drugs or supplements that might affect cardiovascular health for at least six weeks prior to treatment, and were instructed to avoid eating isoflavone-rich legumes such as soy throughout the study. At the end of each period (run-in, placebo, and two active periods), researchers measured arterial compliance using ultrasound, as well as isoflavonoid absorption and serum cholesterol levels.
The results of the study revealed a statistically significant increase in arterial compliance in the red clover group, compared to placebo (a value of 23.7 versus 16 in the placebo group). No side effects were reported. The effects on heart health were similar to those of a 1998 placebo-controlled study on hormone replacement therapy (HRT), which found a 24 percent greater value in arterial compliance in those taking HRT. The results of red clover treatment are especially impressive considering the number of serious side effects associated with HRT, such as an increased risk of depression, high blood pressure, breast cancer, and other problems. In this study, there was also a 10 percent downward trend in the ratio of harmful LDL cholesterol (which decreased) versus healthful HDL levels (which increased), although the change was not statistically significantly different from placebo measurements. There appeared to be little difference between the effects of the two dosage schedules (40 and 80 mg of isoflavones) tested in this study.
An important drawback to this study was the small sample size of 17 participants, which included a placebo group of only three women. Data from the placebo group was not subjected to statistical analysis because of the small number of subjects. Interestingly, the placebo group originally included five women until two dropped out, citing a return of "intolerable menopausal symptoms requiring hormone replacement treatment." Although this study was not specifically designed to test red clover's effects on menopausal symptoms such as hot flashes, it is interesting to note that no one taking red clover dropped out due to uncomfortable menopause-related complaints.

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