Safety of soy-based formulas containing isoflavones: the clinical evidence Merritt RJ, Jenks BH. Journal of Nutrition. 2004;134:1220S-1224S.

Introduction Isoflavones are a naturally-occurring plant A phytoestrogen is a chemical compound found in all soy-based infant formulas. compound that occurs naturally Because isoflavones are a type of phytoestrogens, in plants, such as soybeans, or and largely as a result of research in animal models, plant products, such as whole concerns have been voiced about the safety of grain cereals, and has estrogenic isoflavone-containing, soy protein-based formulas. properties.

Clinical Review Purpose This review presents the clinical data relevant to controversial aspects of feeding soy protein-based formulas. The five areas of interest addressed by this review include: Nutritional adequacy Reproductive development Neurobehavioral developmentt Immune function Thyroid disease

Review Summary This paper systematically explores the debates surrounding soy protein-based : Nutritional adequacy: extensive clinical data have shown that soy protein-based formulas provide good nutrition to the infant even during the most rapid phase of growth. No adverse effects on growth have been observed in infants while consuming soy protein-based formula or after consumption of soy protein-based formula.1-3 Reproductive development: there is complexity in applying observations of isoflavone exposure in animal models to human populations. Knowledge gaps that limit the ability to learn from some animal studies include between-species metabolism differences and differences in exposure levels of isoflavones between animal models and humans.4,5

For Internal Use Only Neurobehavioral development: a large, retrospective cohort study (n=811) of adults who had consumed either soy protein- based formula or cow -based formula as infants showed no difference in educational outcome (as measured by level of highest education) between these two groups.3 Immune function: some studies based on mice or early studies using soy flour-based formula had shown reduced immune function (in mice) or poor response to polio vaccine (in human infants). The mouse studies were not controlled (i.e. no untreated mice, or mice treated with a placebo) and did not take into account the stress of the actual testing (daily injections for 35 days); the early studies of soy flour-based formula are no longer relevant. More recent studies of modern soy protein-based formula showed that these formulas supported normal immune system development in young, growing infants—including normal immune response to oral polio vaccine.1,6-8 Thyroid disease: most thyroid issues were associated with the use of soy flour-based formulas. These formulas were replaced in the 1970s with soy protein isolates fortified with iodine.

Review Findings In all five areas addressed, in-depth reviews of published preclinical and clinical study results have found that there is no conclusive evidence from animal or human adult or infant populations to indicate that dietary isoflavones may adversely affect human health, development, or reproduction.

Key Finding: Discussion The clinical evidence from Soy protein-based infant formula has a long history of safe human populations—both adult use as a plant-based protein alternative for infants. While large and infant—shows that soy prospective or retrospective long-term studies involving more than protein-based infant formulas a few hundred infants fed soy protein-based infant formula do not are a safe alternative to exist, all of the available evidence indicates that these formulas milk or cow milk-based formula are safe. Conclusions Soy-based infant formula is well recognized as a healthy alternative to human or cow’s milk. Recent in-depth reviews of the safety of dietary isoflavones in soy have found that there is no conclusive evidence from animal, human adult, or infant populations to indicate that dietary isoflavones adversely affect human health development or reproduction.

For Internal Use Only References 1. Lasekan JB, Ostrom KM, Jacobs JR, et al. Growth of newborn, term infants fed soy formulas for 1 year. Clin Pediatr (Phila). 1999;38:563-571. 2. Hillman LS, Chow W, Salmons SS, et al. Vitamin D metabolism, mineral homeostasis, and bone mineralization in term infants fed human milk, cow milk-based formula, or soy-based formula. J Pediatr. 1988;112:864- 874. 3. Strom BL, Schinnar R, Ziegler EE, et al. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. J Am Med Assoc. 2001;286:807-814. 4. Safford B, Dickens A, Halleron N, et al. A model to estimate the oestrogen receptor mediated effects from exposure to soy isoflavones in food. Regul Toxicol Pharmacol. 2003;38:196-209. 5. Clark J. Female reproductive and toxicology of estrogen. In: Korach K, ed. Reproductive and Developmental Toxicology. New York: Marcel Dekkar; 1998. 6. Businco L, Bruno G, Giampietro PG, et al. No oestrogen hormonal effects in long-term soy formula fed children [abstract]. J Allergy Clin Immunol. 1999;103 (1 Part 2):S169. 7. Cordle C, Winship T, Schaller J, et al. Immune status of infants fed soy- based formulas with or without added nucleotides for 1 year: part 2: immune cell populations. J Pediatr Gastroenterol Nutr. 2002;34:145-153. 8. Ostrom KM, Cordle CT, Schaller JP, et al. Immune status of infants fed soy-based formulas with or without added nucleotides for 1 year: part 1: vaccine responses, and morbidity. J Pediatr Gastroenterol Nutr. 2002;34:137-144.

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