Isoflavones reduction

An inverse correlation between thyroid cancer risk and phytoestrogens was recently proposed as a result of a multi-ethnic population-based case control study conducted in the San Francisco Bay Area (Hom-Ross et al., 2002). In this study, dietary habits and phytoestrogen consumption were assessed by a food-frequency questionnaire and by a nutrient database. The outcome of the study was that soy-based foods and alfalfa sprouts were associated with a reduction of thyroid cancer risk, whereas a Western diet did not influence cancer risk. No difference was observed between American and Asian women or between pre- and postmenopausal women. Furthermore, among the few compounds examined, the isoflavones genistein and daidzein and the lignan secoisolariciresinol were the phytoestrogens most frequently associated with risk reduction (Horn-Ross et al., 2002). 

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. 

In 1999, the US FDA allowed health claims (on food labels) on the association between soy protein and reduced risk of coronary heart disease for foods containing >6.25 g of soy protein, assuming either four servings, or that a total of 25 g of soy protein are consumed daily. Furthermore, in 2002, the UK Joint Health Claims Initiative approved a health claim on the association between soy protein and cholesterol reduction, the inclusion of at least 25 g of soy protein per day, as part of a diet low in saturated fat, can help reduce blood cholesterol levels and it is important to note that this claim relates to soy protein that has retained its naturally occurring isoflavones. 

Whilst the reduction of flavones to flavanones is of little practical significance, isoflavones are easily reduced to isoflavanones. However, carefully controlled conditions are necessary if further reduction to isoflavanols and even isoflavans is to be avoided (7lJCS(C)1994). 

Lens aldose reductase has been implicated in the pathogenesis of cataracts in diabetic and galac-tosemic animals. The enzyme catalyzes the reduction of glucose and galactose to their polyols, which accumulate in large quantities in the lens and ultimately lead to mature lens opacities. Several key bioflavones have activity against this enzyme. Oral administration of quercitrin decreased the accumulation of sobital in the lens. Therefore, the accumulation of lens opacities could be partially abrogated by certain flavonoids. In a study of 30 flavones, 4 isoflavones, and 13 coumarins, many potent inhibitors were found, but 5,7,3, 4 -tetrahydroxy-3,6-dimethoxyflavone and 6,3, 4 -trihy-droxy-5,7,8-trimethoxyflavone were especially active. 

Chromones, flavones, and isoflavones of general types 396 and 398 have been reported to undergo reduction with nickel borohydride in dry methanol at ambient temperatures to give the corresponding 277-l-benzopyran-4-ols in good yields. In all cases studied, the products obtained were found to be the air-stereoisomers, for example, 397 and 399 (Scheme 64) <2002JCM201>. 

Anthony et al., 1997) cause significant reductions in serum TC and triglyceride (TG). In non-human primates, dietary genistein, the isoflavone significantly reduces plasma LDL and VLDL cholesterol levels (Anthony et al., 1997). 

There appears to be a strong link between arterial compliance or stiffness and atherosclerosis and systolic hypertension. In humans, supplementation with soy protein or isoflavones appears to improve com-pliance. In one placebo controlled, randomized, cross-over clinical trial on peri- and postmenopausal women, treatment with 80 mg/day purified soy isoflavones for 5 weeks resulted in improvement of ca. 26% in systemic arterial compliance, even though there was no reduction in blood lipids. Only one study demonstrated a significant decrease in blood pressure, reported in 51 non-hypertensive women after ingestion of 34 mg/day isoflavones,but other studies failed to show a significant effect. ... 

One trial using 80 mg daily of isoflavones from red clover reported a 44 /o reduction in hot flushes, while another study reported no clinically important effects on either hot flushes or other menopause symptoms. ... 

All isoflavones [daidzein (27), genistein (28)] and isoflavanones (17, 86-93) did not stimulate nitric oxide production by mouse macrophage-like Raw 264.7 cells, but almost completely inhibited NO production by the lipopolysaccharide (LPS)-activated Raw 264.7 cells. ESR spectroscopy showed that secundifloran (88) and secundiflorol D (90), which showed the most inhibitory effect for NO production, efficiently scavenged the superoxide anion and NO radicals. From these results, it is suggested that the inhibition of macrophage NO production by these isoflavanones might, at least in part, be explained by their radical scavenging or reduction activity (Fig. 17) (Tables 3, 4) [16]. 

Epidemiological studies (Aldercreutz et al., 1991 Aldercreutz, 1998) indicate that consumption of tofu and other soy foods may be associated with the low incidence of breast cancer in Japanese women. This discovery has led numerous researchers in recent years to search for the biochemical components in soybean that are responsible for the cancer risk-lowering effect. Aside from the potential cancer prevention effect (Wu et al., 1996 Cline and Hughes, 1998 Griffiths et al., 1998 Messina and Bennink, 1998 Stephens, 1999), isoflavones also have been found to have other potential health benefits, including heart disease prevention (Anthony et al., 1998), bone mass density increase to prevent osteoporosis (Anderson and Camer, 1997) and the reduction of postmenopausal syndromes in women (Knight et al., 1996). 

The North American Menopause Society position statement for treatment of mild menopause-associated vasomotor symptoms recommends first trying lifestyle changes, either alone or in combination with nonprescription remedies such as dietary isoflavones, black cohosh, or vitamin E. Studies suggest that there is a modest reduction in vasomotor symptoms with soy supplementation and that higher doses of soy isoflavones may be needed. Black cohosh does not have phytoestrogenic effects, and the evidence of its efficacy for menopausal symptoms is Dong quai, a traditional... 

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