Title: The risks and benefits of the isoflavones in women’s health
Key words: isoflavones, plant phenols, oestrogen, oestrogenic, oestrogen-like, HRT, menopause, menopausal, pre-menopausal peri-menopausal, soya, oestrogen receptors, menstrual cycle, LH, FSH, osteoporosis, CVD, cardiovascular disease, calcium, lipid peroxidation, follicular phase, flushing, cholesterol, lipid, atherogenic, soya protein, antioestrogenic, antioxidant, antimitotic, antiprotease, antiangiogenesis, diethyloestrogen,
Date: Sept 2006
Author: Morgan, G
The risks and benefits of the isoflavones in women’s health
Isoflavones, a class of plant phenols, have been extensively investigated in recent years due to their oestrogen-like properties. Like HRT they have been linked with favourable health benefits in menopausal women. Their use as HRT replacements and their possible side effects in this age group and in children will be reviewed here.
Isoflavones possess weak oestrogenic properties, but, in the quantities ingested in the Far Eastern diet in the form of soya-derived products, they promote significant biochemical and physiological effects (White 2000). Their effects are mediated through oestrogen receptors for which they compete with endogenous oestrogen. They selectively bind to oestrogen beta-receptors found in brain, bone, bladder and the vascular endothelium (Kuiper 1997). This may partly explain their beneficial oestrogenic effects though it is known that isoflavones can also exert a modulating influence on endogenous oestrogen activity (Xu 2000).
Direct oestrogenic effects on the menstrual cycle occur with isoflavone use. Inhibition of LH and FSH secretion, prolongation of the follicular phase and menstrual cycle and some reduction in menopausal flushing has been demonstrated (Cassidy 1994, Brzezinski 1997). Indirect effects are reflected in the reduced incidence of osteoporosis and cardiovascular disease amongst soya consumers (Potter 1998, Alekel 2000, Somekawa 2001, Setchell 1995, Anderson 1995).
Laboratory experiments have shown isoflavone effects on calcium, lipid and protein metabolism, oxidative pathways, lipid peroxidation, the migration of vascular smooth muscle cells and on cell differentiation. It seems likely that these effects explain the ability of isoflavones to lower blood cholesterol, normalise lipid profiles and prevent the atherogenic process (Crouse 1999, Washburn 1999,Tikkanen 1998). Some of these effects may be directly metabolic and not oestrogen-mediated. In the case of osteoporosis, some of the efficacy of soya consumption has been shown to be due to inhibition of urinary calcium excretion by soya protein (Breslau 1988). This highlights the point that isoflavones, soya and confounding factors should be all considered in any analysis of these issues.
The oestrogenic effects of isoflavones has raised concerns that these compounds might promote the development of oestrogen-dependant tumours such as breast and endometrial cancer. Petrakis, in a frequently quoted study (Petrakis 1996), reported increased epithelial proliferation and glandular secretion in breast tissue exposed to isoflavones but this study has been criticised for its design and conclusions. Another study (Panno 1996) showed reduced mitotic activity in breast cells exposed to physiological levels of endogenous oestrogens and isoflavones. In animal models prepubertal exposure to isoflavones, though associated with ductal hyperplasia, was associated with a reduced incidence of adult cancer of the breast (Murrill 1996, Fritz 1998).
In humans an epidemiological survey of Japanese Americans indicated that those exposed to soya from birth showed a reduced incidence of cancer extending into the menopause (Wu 1998). There are no studies indicating that soya consumption initiated in the premenopausal period is associated with an increased cancer risk. Much in vivo research attests to an antioestrogenic and anticancer effect of the isoflavones associated with antioxidant, antimitotic, antiprotease and antiangiogenesis effects (Wei 1995, Lamartiniere 1995, Akiyama 1987, Supko 1995) which supports their safety.
Concerns have also been voiced about the advisability of soya milk consumption during infancy and childhood. There was a fear that oestrogenic effects might, as exhibited by the synthetic oestrogen diethyloestrogen, be associated with developmental disorders of the genital tract or later menstrual disorders and carcinogenesis. Consumption in infancy leads to much higher plasma isoflavone levels than in adults (Setchell 1997) but, in spite of this and after many years of soya milk use in clinical practice, there are no validated surveys documenting any ill effects.
Finally, studies indicate a quantitative benefit to soya consumption. Animal and epidemiological studies show not only benefits from early consumption but also from higher levels of consumption. Intakes of above 50mgs per day have been shown to produce significant improvements in bone and cardiovascular health in women, particularly in the postmenopausal group (Potter 1998, Somerkawa 2001, Crouse 1999). These are levels which are unlikely to be reached by a Western diet and raise the question of the future therapeutic use of functional foods or supplements in the West.
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