Effects of phyto-oestrogens on tissues (1999)

Recent investigations on the effects of phyto-oestrogens on various tissues have revealed that these diverse molecules may improve human health, particularly by protecting against certain chronic diseases. After a brief examination of the food sources, structures, and general cellular actions of the major phyto-oestrogens, current research findings on cardiovascular disease, skeletal tissues, and reproductive cancers are reviewed. Phyto-oestrogen concentrations in blood may be maintained at high levels in those consuming soyabean (Glycine max)-based food daily at several meals and exert their effects on target cells through either genomic effects via the classical oestrogen receptors or non-genomic effects mediated by membrane-bound oestrogen receptors or other cellular proteins. The expression of oestrogen receptor (OR) subtypes alpha (a) and beta (beta) varies across tissues, and cells that preferentially express OR-beta, which may include bone cells, are more likely to respond to phyto-oestrogens. Conversely, reproductive tissues contain relatively more OR-a and may, thus, be differently affected by phyto-oestrogens. Soyabean phyto-oestrogens appear to prevent the progression of atherosclerosis through multiple interactions, including lowering of plasma lipids and lipoproteins, increased vasodilatation and, possibly, decreased activation of blood platelets and vascular smooth muscle cells. However, a favourable impact on cardiovascular disease morbidity and mortality by a soyabean-enriched western-type diet remains to be shown, and unresolved questions remain regarding dose and form of the phyto-oestrogens in relation to risks and benefits. The isoflavones of soyabean have been shown consistently to have bone-retentive effects in animal studies by several investigators using rodent models, although intakes must be above a relatively high threshold level for a lengthy period of time, and little or no extra benefit is observed with intakes above this threshold level. The reports of modest or no effects on prevention of bone loss in human and non-human primate studies respectively, may be due to the limited doses tested so far. The relationship between soyabean-food intake and cancer risk has been more extensively investigated than for any other disease, but with less certainty about the benefits of long-term consumption of phyto-oestrogen-containing foods on prevention of cancer. The observations that breast and prostate cancer rates are lower in Asian countries, where soyabean foods are consumed at high levels, and the high isoflavone content of soyabeans have led to examination of the potential protective effects of phyto-oestrogens. Establishing diet-cancer relationships has proved difficult, in part because of the conflicting data from various studies of effects of soyabean-diets on cancer. Epidemiological evidence, though not impressive, does suggest that soyabean intake reduces breast cancer risk. The isoflavone genistein has a potent effect on breast cancer cells in vitro, and early exposure of animals to genistein has been effective in reducing later development of mammary cancer. Thus, continuous consumption of soyabean foods in early life and adulthood may help explain the low breast cancer mortality rates in Asian countries. Although the evidence for a protective effect against prostate cancer may be slightly more supportive, more research is needed before any firm conclusions can be made about the phyto-oestrogen-cancer linkages.