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No Hormonal Effects Observed in Infants on Soy Formula

June 4, 2021

by Dr. Mark Messina

This blog rarely discusses research on soy infant formula (SIF). There are many reasons for not doing so. For example, on a body weight basis, isoflavone exposure is much higher in infants fed SIF than in children or adults consuming soyfoods in amounts compatible with Japanese consumption.1,2 Also, during the first few weeks and months of life (prior to the introduction of foods or non-formula beverages), infants are likely more sensitive to hormonal influences than are children or adults.3-6 This point has been highlighted by the U.S. National Institute of Environmental Health Sciences7 and the Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals.8

Because of the greater exposure during a more sensitive period of life, any hormonal effects observed in infants fed SIF do not necessarily apply to children consuming soyfoods. However, research demonstrating no hormonal effects in infants fed SIF suggests effects will not be observed in children consuming soyfoods. That is why recent research from Chin and colleagues 9 is so intriguing. They set out to determine whether SIF would disrupt minipuberty in boys. In boys, minipuberty involves a rise in serum luteinizing hormone and testosterone, and stimulation of reproductive organ development.

The Infant Feeding and Early Development study is a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow-milk formula, or breastmilk feeding during study follow-up. Reproductive hormone concentrations and male anatomical measurements were longitudinally assessed from birth to 28 weeks. The results revealed there were no differences in the trajectories of hormone concentrations or anatomical measures between boys fed SIF (n=55) and boys fed cow-milk formula (n=54). Compared with breastfed boys (n=38), SIF-fed boys had a more rapid increase in penile length and slower initial lengthening of anogenital distance (p=0.03), but no differences in hormone trajectories.

A second recent publication also addresses the potential hormonal effects of soy in young people. Oliveira et al.10 conducted a systematic review to determine the impact of a soy-based infant diet on the onset of puberty in girls (thelarche, pubarche, and menarche age), boys (pubarche, voice change, testicular, and penis enlargement age), and both (risk of delayed and precocious puberty). Eight studies were included in the analysis, 598 children were said to consume a soy-based diet and 2,957 did not. There was no statistically significant effect of soy feeding on risk of precocious puberty and no between-group difference was observed in menarche age. The authors concluded they did not find an association between a soy-based infant diet and the onset of puberty in boys or girls.

However, there are several important weaknesses to the analysis by Oliveira et al.10 that warrant mention. First, although the title of the article refers to “soy-based infant diet,” two of the eight studies used adolescent soyfood intake as a surrogate for childhood intake, not intake during infancy. A German study assessed soy intake of girls 7-9 years of age; furthermore, isoflavone intake was negligible (<1mg/d). And, in a Columbian study, children ages 7-9 consumed a soy supplement that provided 7g soy protein. Although information on the isoflavone content of the protein was not provided, it likely contained no more than 1mg/g protein. Given the limitations of this analysis, the conclusion that there was no association between a soy-based infant diet and the onset of puberty in boys or girls should be viewed with extreme caution.

In conclusion, newly published research shows SIF does not exert hormonal effects in boys. A systematic review concluded there is no association between soy-based infant diet and the onset of puberty in boys or girls, but because of the limitations of this research, its informative value is unclear.

References

  1. Badger TM, Ronis MJ, Hakkak R, et al. The health consequences of early soy consumption. J Nutr. 2002;132:559S-65S.
  2. Setchell KD, Zimmer-Nechemias L, Cai J, et al. Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet. 1997;350:23-7.
  3. Patisaul HB. Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours. Proc Nutr Soc. 2017;76:130-44.
  4. Yilmaz B, Terekeci H, Sandal S, et al. Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention. Rev Endocr Metab Disord. 2019.
  5. Jefferson WN, Patisaul HB, Williams CJ. Reproductive consequences of developmental phytoestrogen exposure. Reproduction. 2012;143:247-60.
  6. WHO & UNEP. State of the Science of Endocrine Disrupting Chemicals — 2012 (World Health Organization, 2013).
  7. Soy infant formula. National Institute of Environmental Health Sciences. Accessed November 17, 2019. https://www.niehs.nih.gov/health/topics/agents/sya-soy-formula/. In.
  8. Gore AC, Chappell VA, Fenton SE, et al. EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr Rev. 2015;36:E1-E150.
  9. Chin HB, Kelly A, Adgent MA, et al. Reproductive hormone concentrations and associated anatomical responses: does soy formula affect minipuberty in boys? J Clin Endocrinol Metab. 2021.
  10. Oliveira FRK, Gustavo A, Goncalves RB, et al. Association between a soy-based infant diet and the onset of puberty: A systematic review and meta-analysis. PloS one. 2021;16:e0251241.