J Clin Endocrinol Metab. 2006 Mar;91(3):772-80.
Clinical review: a critical evaluation of the role of soy protein and isoflavone supplementation in the control of plasma cholesterol concentrations.
Dewell A, Hollenbeck PL, Hollenbeck CB.
Department of Nutrition and Food Science, San Jose State University, One Washington Square, San Jose, California, USA.
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CONTEXT: The purpose of this review was to critically evaluate current research on the effect of soy protein and isoflavone supplements on plasma lipoproteins and place the potential role of soy in the prevention of coronary artery disease (CAD) into a clinical perspective. EVIDENCE ACQUISITION: An extensive literature search was performed using a variety of medical and scientific databases including Medline, PubMed, Science Direct, Ovid, NIST, and Infotrac to identify relevant articles. Journal articles were cross-referenced for additional sources of information. Articles were evaluated based on level of experimental control as well as statistical, quantitative, and clinical analysis. EVIDENCE SYNTHESIS: Soy and soy isoflavones have been the object of extensive research investigating their potential hypocholesterolemic effects and possible role in the prevention of CAD. It has been suggested that soy, especially the isoflavones contained in soy, improves lipoprotein levels, thus reducing the risk for CAD. This belief, however, is not uniformly accepted. Moreover, the experimental evidence in support of this notion is not as overwhelming as generally perceived, and the current available data reveal that the discrepancies observed are primarily statistical in nature rather than reflecting actual quantitative differences in the hypocholesterolemic effects detected. CONCLUSIONS: A critical analysis of the investigations to date indicates the data are not quantitatively impressive and raises substantial questions about the clinical importance of the hypocholesterolemic effects observed.

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Isoflavones are a class of phytoestrogens, a group of nonsteroidal plant chemicals with estrogen-like activity. The chemical structures of 17beta-estradiol and equol (a phytoestrogen metabolite) are so similar that they are virtually superimposable (Fig. 1). Specifically, the presence of the phenolic ring and the distance between the hydroxyl groups, which is nearly identical, are considered prerequisites for estrogen binding (39). The estrogenic activity of genistein and daidzein, the predominant isoflavones in soy, is 10^–2 to 10^–3 that of 17beta-estradiol (40). However, their concentration in the plasma in individuals consuming the amount of soy present in the traditional Japanese diet (50–80 mg/d) can be 100 times higher than the concentration of endogenous estrogens (41). Thus, plasma concentrations of these phytoestrogens would put them in a range consistent with endogenous estrogen effects. It is this chemical and structural similarity to endogenous estrogens that led to the hypothesis that isoflavones may be responsible for the hypocholesterolemic effect of soy (39).

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It is also necessary to point out that not all of the evidence demonstrates beneficial effects from increased soy consumption; the potential adverse effects of soy have been well described (50, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86). Soybeans are rich in antinutrients including protease inhibitors (trypsin and chymotrypsin), lectins (hemaggluttinins), goitrogens, phenolic compounds (tannins and phytoestrogens), phytates, saponins, and antivitamins (to vitamins A, B12, D, and E) (76). These antinutrients have been associated with growth retardation and failure to thrive, pancreatic hypertrophy, hyperplasia and hypersecretion, pancreatic acinar adenomas, and endocrine abnormalities (76, 77, 78, 79, 80, 81, 82). Trypsin inhibitors and lectins are both growth inhibitors. Trypsin is important not only as a protease but also is responsible for the activation of other pancreatic proenzymes (zymogens), whereas lectins are capable of inhibiting growth by binding specific cell-surface receptors on small intestine epithelial cells (as well as lymphocytes) (76, 78, 79, 80, 81). Although high-temperature cooking can reduce some of these growth inhibitors, it does not completely eliminate them (76). In addition, soy has one of the highest concentrations of phytates, an antinutrient that has been shown to block the uptake of several essential elements including calcium, magnesium, copper, iron, and zinc. The phytates present in soy appear to be highly resistant to normal phytate-reducing processes (76, 80, 81).

Concentrations of soy isoflavones in the range of levels found with consumption of soy-based diets have been shown to inhibit thyroxine synthesis inducing goiter and hypothyroidism in infants fed soy-based formulas, in some cases leading to the development of autoimmune thyroid disease (81). In addition, potential harmful effects of soy isoflavones have been recently reported in adults. A recent prospective epidemiological study reported that increases in tofu consumption may lead to increased cognitive dysfunction in Japanese American men (82). Finally, high concentrations of genistein, daidzein, and other isoflavones have been reported to result in genetic abnormalities in a variety of cells including human lymphocytes, oviduct cells, and testis cells and therefore may possess potentially genotoxic effects (50). Although research in many of these areas is not yet well developed, it should raise a note of caution in terms of recommendations to dramatically increase soy consumption or encourage the supplemental use of soy.

Conclusion

A critical evaluation of the evidence currently available in the literature on the potential role of soy protein or isolated soy isoflavone supplementation for improving plasma lipoproteins indicates that the data are not quantitatively impressive and raise substantial questions about the clinical importance of the hypocholesterolemic effects. Therefore, it would appear that conclusions in regard to the hypocholesterolemic benefits of soy made by researchers (1, 2, 12) and health agencies (9, 10) are perhaps too premature to make any recommendation for their use as an alternative to established therapies in the management of hypercholesterolemia in populations at risk for CAD (87).

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Categories: 2006, Soy, Cholesterol, Antinutrients, Phytates, Lectins, Growth velocity, Failure to thrive, Endocrine, Phytoestrogens, Thyroid, Hypothyroidism, Trypsin inhibitors, Nutrition and diet