Red clover-derived isoflavones

Atkinson C, Warren RML, Sala E et al. Red clover-derived isoflavones and mammographic breast density a double-blind, randomized, placebo-controlled trial. Breast Cancer Res. 6, R170-R179, 2004. 

Red clover herb and flower contain approximately 0.17% isoflavones (DerMarderosian and Beutler 2005), with the herb generally containing a higher percent isoflavone content than the flower (Booth et al. 2006). Commercially available red clover products include products with this normal percentage of isoflavones and those modified to contain up to 100% isoflavones. Products with modified concentrations of selected compounds may be expected to have different physiological effects than traditional preparations of the herb. Information on both red clover and red clover derived isoflavones is provided in this entry. 

In a noncontrolled clinical study of postmenopausal women administered 80 mg daily of red clover-derived isoflavone extract for 6 months, some changes in endometrial activity but no changes in endometrial thickness were observed. Of the 32 study participants, 6 presented with vaginal bleeding and 3 presented with endometrial alteration as compared to the initial exams, 2 developed endometrial cell proliferation, and 1 developed endometrial hyperplasia (Wolff et al. 2006). 

Abebe, W. 2002. Herbal medication Potential for adverse interactions with analgesic drugs. /. Clin. Pharm. Ther. 27(6) 391-401. Atkinson, C., R.M. Warren, E. Sala, et al. 2004. Red-clover-derived isoflavones and mammographic breast density A doubleblind, randomized, placebo-controlled trial. Breast Cancer Res. 6(3) R170-R179. 

Red Clover Derived Isoflavones Metabolism and Physiological Effects in Cattle and Sheep and their Concentrations in Milk Produced for Human Consumption... 

Atkinson C, Oosthuizen W, Scollen et al. Modest 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 women. J. Nutr. 134, 1759-1764, 2004. 

In ovariectomized rats administered 20 or 40 mg daily of red clover-derived total isoflavones for 14 weeks, treatment with isoflavones significantly increased bone mineral content, mechanical strength of the tibia, femoral weight, and femoral density and prevented the rise of serum alkaline phosphatase levels. In addition, the treatment with isoflavones significantly reduced the number of osteoclasts compared with the ovariectomized control rats (Occhiuto et al. 2007). 

A red clover-derived extract of 30% isoflavone agly-cones was shown to bind to mu- and delta-opiate receptors in Chinese hamster ovaries (Nissan et al. 2007). 

Red clover is a plant that contains isoflavones in a slightly different composition compared with soy. Red clover contains formononetin and biochanin A, which are not present in soy and may thus have additional biological activity. So far, four studies (Barber et ah, 1999 Knight et ah, 1999 van de Weijer, 2002 Tice et ah, 2003) have been performed using isoflavones derived from red clover (Table 4.3). These have used doses of isoflavones ranging from 40 to 160 mg. Three out of four of these studies did not show any effects, even in spite of a very large sample size (Tice et ah, 2003). Only one study showed a reduction in the number of hot flushes. The reduction, however, was small (van de Weijer and Barentsen, 2002). Red clover therefore does not appear to have much of an effect on the reduction of hot flushes. 

Effects of isolated isoflavones derived from red clover. 

Tamura, S., Chang, C., Suzuki, A., Kymai, S. Isolation and structure of a novel isoflavone derivative in red clover. Agri Biol Chem 1967 31 1108-1109. 

A review of studies on red clover and soy-derived isoflavones concluded that 2 mg/kg was a safe daily dose of isoflavones for most populations (Barnes 2003). A second review of studies on red clover and soy-derived isoflavones indicated that 40-50 mg of isoflavones is recommended as the daily dose. This recommendation was based on the daily intake of isoflavones in a traditional Japanese diet (Beck et al. 2005). 

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