Of all the functional components present in soybean, soy isoflavones are the most investigated biomolecules of the last decade (Rochfort and Panozzo, 2007). They are flavonoid compounds with two benzyl rings (C6) joined by a three-carbon chain. Major isoflavones in soybean exist in four forms: (i) as free aglycones (genistein, daidzein and glycitein) (Fig. 17.1); (ii) as P-glucosides when sugar moiety is attached to aglycone; (iii) as malonyl; and (iv) as acety-lated derivatives of P-glucosides.
Twelve isomers are present in the seed, but they are converted back to their corresponding aglycones in the human gut prior to absorption (Setchell and Classidy, 1999). The concentration of total isoflavones ranges from 1 to 3 mg g-1. This varies depending upon the genotype and environmental conditions (Kumar et al., 2007a; Rebeiro et al., 2007). Different processing methods have also been reported to influence the levels of isoflavones in soy food (Coward et al., 1998). Studies also indicate that cultural practices such as increased doses of fertilizer and irrigation enhance their concentration in soybean seeds (Vyn et al., 2002; Bennett et al., 2004). It would not be wrong to attribute the increased interest in soy-derived foods to the increased discovery of the protective effects of isoflavones against several killer diseases of this century. Some are given in detail below.
Incidences of breast cancer, a common disease in western countries, are now on the rise in other parts of the world also. Barnes et al. (1990) was the first to show that a soybean diet reduces the incidence of mammary tumours in rats. Subsequently, several epidemiological studies indicated the inverse relationship between breast cancer and soy food intake (Lee et al., 1991; Pisani et al., 2002; Wu et al., 2008). Isoflavone supplements (40 mg day-1)
result in a decrease in breast tissue density in post-menopausal women (Atkinson and Bingham, 2002). Being structurally similar to endogenous estrogen, isoflavones bind to estrogen receptors and exert an estrogen-like effect (Beard et al., 1996). Kurzer (2002) showed that consumption of 65 mg isoflavones day-1 favourably affected estrogen metabolism. Soy isoflavones have also been implicated in the prevention and therapy of prostate cancer (Holzbeierlein et al., 2005).
Concerns were raised when isoflavones were found to stimulate cell proliferation in breast-cancer-sensitive cell lines (Zava and Duwe, 1997; Bail et al., 2000). Messina and Wood (2008) addressed these concerns by highlighting the point that isoflavone exposure at levels consistent with the dose in historical Asian soy foods does not elicit adverse stimulatory effects on breast tissue. Estrogenic effects of soy isoflavones have also been implicated in the association of soy food with moderating post-menopausal symptoms such as hot flushes, fatigue and sweating.
By 2020, CVD will be a leading cause of death. The number of deaths due to CVD is projected to pass 20 million year-1. Contrary to earlier beliefs, CVD is not confined to developed countries; developing economies such as India and China together account for more deaths due to CVD than the developed countries of the world combined. Soy proteins reduce the risk of heart stroke, heart arrest, atherosclerosis and so on. Anderson et al. (1995) conducted a meta-analysis of the effects of soy protein intake on serum lipids. They found that an average consumption of 47 g day-1 soy protein led to a significant reduction in total cholesterol (9%), low-density lipoprotein (LDL) cholesterol (13%) and triglycerides (11%). Subsequently, a meta-analysis of eight randomized controlled trials in human subjects attributed these lipid-lowering effects to soy isoflavones (Zhou et al., 2004).
However, contradictions persist concerning the potential mechanisms of the lipid-lowering actions of soy isoflavones. Oxidative damage to the cellular lipids is a significant contributor to the development of CVD. Lipid peroxidation of PUFA is associated with the formation of hydroperoxides, free-radical intermediates and secondary oxidation products, which are excreted in urine. Fritz et al. (2003) found very low concentrations of secondary lipid oxidation products - aldehydes and carbonyl compounds (the biomarkers of lipid peroxidation) - in the urinary excretions of ten healthy women who were fed dietary soy isoflavones. This study implicated the role of in vivo antioxidant activities of soy isoflavones in reducing the risk of CVD. Apart from LDL cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol and apolipoproteins play no less an important role in predicting heart diseases. People with a normal LDL cholesterol level but high levels of apolipoprotein B are at high risk for CVD. Apo-lipoprotein A-1 provides a protective effect against heart attack similar to that of HDL cholesterol. Some clinical studies have speculated about the role of soy isoflavones in reducing the risk of CVD by modulating levels of apolipoproteins, but the reports were inconsistent (Psuka et al., 2002; Hall et al., 2006; McVeigh et al., 2006).
Type 2 diabetes is reaching epidemic proportions worldwide, with developing country such as India alone accounting for 40 million patients. Studies have suggested a role for isoflavones in reducing the risk of the disease (Jayagopal et al., 2002; Ali et al., 2005; Nordentoft et al., 2008). Chronic kidney disease is also increasing at a rapid rate consequent to the increasing incidence of diabetes. Stephenson et al. (2005) reported that 40% of new cases of renal disease are related to diabetes. While reviewing studies pertaining to the beneficial effects of soy protein consumption for renal function, Anderson (2008) concluded that the role of soy isoflavones and soy peptides in improving renal function in diabetic neuropathy should be investigated.
Osteoporosis, literally meaning 'porous bone', is a metabolic disease of bone characterized by low bone mass and deterioration of bone tissues, making the individuals prone to fracture. This is a global disease affecting 150 million individuals worldwide, cutting across ethnicity and race. Although an inadequate intake of calcium and vitamin D, unhealthy lifestyles marked by excessive alcohol and tobacco consumption and lack of exercise have been cited as some of the causes of the disease, the onset of menopause with a concomitant decline in estrogen renders women prone to the disease. Worldwide, the population of postmenopausal women is expected to reach 1.2 billion by 2030, indicating the magnitude of the problem that will exist in just a few years from now. Messina et al. (2004) reviewed studies showing a positive effect of soy product intake on bone health. Several studies looking at the role of soy isoflavones on bone mineral density have been conducted with peri- or postmenopausal women (Nagata et al., 2002; Branca, 2003). Recently, Song et al. (2008) showed that a 1 mg day-1 intake of isoflavone resulted in increases in bone mineral density of 0.26% in the femoral neck and 0.31% in Ward's triangle in young Korean women.
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