Background:A casein hydrolysate infant formula has been shown to be associated with lower levels of neonatal jaundice than are standard infant formulas. Because β-glucuronidase is related to neonatal jaundice, this study examined the effect of a casein hydrolysate formula on β-glucuronidase.Methods:β-glucuronidase activity was measured with or without added dietary components. The β-glucuronidase sources used were meconium, breast milk, and the purified bovine liver enzyme. The dietary components assayed for their effect on β-glucuronidase activity included casein hydrolysate formula (Nutramigen), whey-predominant formula (Enfamil), breast milk, enzymatically hydrolyzed casein, and other constituents of the casein hydrolysate formula. Stool samples of 6-day-old infants, who were exclusively fed one of the two formulas or breast milk, were also assayed for inhibition of β-glucuronidase.Results:Only Nutramigen, enzymatically hydrolyzed casein, and stool from Nutramigen-fed infants consistently demonstrated significant inhibition of β-glucuronidase activity, ranging from 45% to 85% of that in controls. The inhibition of β-glucuronidase in purified bovine liver demonstrates a dose response in a pH range from 4 to 7.3.Conclusions:Hydrolyzed casein contains a β-glucuronidase inhibitor that, in casein hydrolysate-fed infants, persists after passage through the digestive tract. These data are consistent with the possibility that inhibition of β-glucuronidase is a mechanism by which infants fed casein hydrolysate have lower jaundice levels than infants fed routine formulas or breast milk. Further study of this mechanism is needed.