Reduction of serum cholesterol by soy proteins: Clinical experience and potential molecular mechanisms

The major components of soybean flour (ie, proteins, fibres, and isoflavones) have been investigated as possibly responsible for the cholesterol-lowering effects of soy-based diets. The evidence for and against the involvement of each component is reviewed. A role for indigestible components has long been ruled out because soybean saponins are unable to bind neutral sterols and bile acids and increase their faecal elimination. A direct role for soy isoflavones seems to be suggested by experiments in monkeys fed with control vs ethanol-treated soybeans. However, in humans, plasma cholesterol reduction has been obtained with protein preparations virtually devoid of isoflavones. Moreover, the major soybean isoflavone, genistein, being an inhibitor of tyrosine kinase, is expected to antagonize the activation of low density lipoprotein (LDL)-receptors, whose up-regulation has been repeatedly shown to be involved in the mechanism of increased LDL degradation by the liver induced by soy and possibly resulting in hypocholesterolaemia. The LDL receptor stimulatory effect will probably be traced to 7S, one of the major soybean proteins, and specifically to one of its subunits, the α chain, which is more effectively catabolized by liver cells than the β chain. To positively establish proteins as the active components of soybean-based diets, ongoing studies aim to link intracellular catabolism in vitro with the physiological pathway of intestinal digestion in vivo, and especially to determine the possible presence in serum of undegraded or partially degraded 7S-derived peptide fragments