Developmental effects and health aspects of soy protein isolate, casein, and whey in male and female rats

Int J Toxicol. May-Jun 2001;20(3):165-74. doi: 10.1080/109158101317097755.


Dietary factors other than the traditional nutrients are found in the so-called functional foods. They are becoming increasingly recognized as potentially important for maintaining good health. Soybeans are rich in such factors thought to help prevent certain chronic diseases. Soy protein isolate (SPI) is one of the three major proteins used in infant formulas sold in the United States, with casein (CAS) and whey (WPH) proteins being the others. We have been studying the health effects of these proteins. Safety concerns have developed over the consumption of soy-based infant formula, partly because of the high circulating levels of the total isoflavones (phytoestrogens) during "critical periods of infant development." There is a paucity of data on developmental, physiological, neurophysiological, behavioral, metabolic, or molecular effects of soy phytochemicals in humans, especially during pregnancy and infancy. We have studied the effects of CAS, SPI, and WPH in short-term, long-term, and multigenerational studies in rats. Aside from minor differences in body weight gain profiles, CAS-, SPI- or WPH-fed rats did not differ in development, organ weights, in vitro hepatic metabolism of testosterone (T), or reproductive performance. However, some endocrine-related functions differed between rats fed these proteins. We found that SPI accelerated puberty in female rats (p < .05) and WPH delayed puberty in males and females, as compared with CAS (p < .05). Gender differences were also found in gonadectomy-induced steroid responses. Male rats had normal serum T levels, but female rats fed SPI had reduced serum 17beta-estradiol concentrations and a blunted 17beta-estradiol response to ovariectomy, as compared to rats fed CAS or WHP (p < .05). Female rats fed SPI or WHP or treated with genistein had reduced incidence of chemically induced mammary cancers (p < .05) compared to CAS controls, with WHP reducing tumor incidence by as much as 50%, findings that replicate previous results from our laboratory. Together, these results suggest gender-specific differences in development and certain endocrine responses among rats fed diets composed of a single protein source such as those used in infant formulas. Whether similar developmental effects occur in human infants is unknown, but unlikely because (1) most infants do not consume such diets throughout life as these rats did, and (2) no such effects have been reported in millions of American infants fed infant formula containing these proteins. The long-term health consequence implications of early diet exposure to SPI and WPH, such as reduced breast cancer incidence, are likely to be very positive.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Caseins / administration & dosage
  • Caseins / pharmacology*
  • Chelating Agents / administration & dosage
  • Chelating Agents / pharmacology*
  • Diet
  • Endocrine System / drug effects*
  • Estradiol / blood
  • Female
  • Male
  • Mammary Neoplasms, Experimental / prevention & control
  • Milk Proteins / administration & dosage
  • Milk Proteins / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sex Factors
  • Soybean Proteins / administration & dosage
  • Soybean Proteins / pharmacology*
  • Testosterone / blood
  • Weight Gain
  • Whey Proteins


  • Caseins
  • Chelating Agents
  • Milk Proteins
  • Soybean Proteins
  • Whey Proteins
  • Testosterone
  • Estradiol