Longer term effects of early dietary cholesterol level on synthesis and circulating cholesterol concentrations in human infants

De novo endogenous cholesterol synthesis is an integral component of developing human infant adaptive mechanisms that regulate cholesterol homeostasis. Smaller central pools of cholesterol later in life may contribute to reduced low-density lipoprotein-cholesterol (LDL-C) concentrations in the plasma and thus reduce the risk of cardiovascular disease. Early infant adaptive mechanisms may theortically result in altered central pools of cholesterol in later life. To examine the response of cholesterol homeostasis to long-term dietary cholesterol supplementation, endogenous cholesterol synthesis was studied in 81 full-term healthy neonates at 4 months or at 11 and 12 months of age. Thirty-two infants were breast-fed (BF) (6 males, 7 females), fed regular cows milk protein-based formula (RF) (6 males, 3 females) 0.85 mmol cholesterol/L (33 mg cholesterol/L), or fed regular cow milk protein-based formula with the addition of cholesterol (RF+cholesterol) (5 males, 5 females) 3.44 mmol cholesterol/L (133 mg cholesterol/L). Effects of cholesterol supplementation on cholesterol synthesis rates were evaluated at 4 months of age. Forty-nine other infants, BF (11 males, 6 females) fed RF (7 males, 12 females), or RF+cholesterol (6 males, 7 females) until 6 months of age were studied to test the hypothesis of imprinting using a cross-over design study with a 1-month 250 mg cholesterol/day challenge at 11 months of age. The incorporation rate of deuterium in body water into erythrocyte-free cholesterol over 48 hours was used as an index of cholesterol fractional synthetic rate (FSR) at 4, 11, and 12 months of age. Both plasma total- and LDL-C were higher (P[lt ] .04) in BF compared with RF+cholesterol and RF formula-fed groups at 4 months of age. Plasma cholesterol concentrations for all 3 groups were similar at 11 and 12 months of age. FSR (pools/d) was 4-fold higher (P[lt ] .0001) in both RF and RF+cholesterol compared with BF groups, but not different between RF and RF+cholesterol formula-fed groups. No differences in FSR before and after cholesterol challenge were observed within the 3 feeding groups at 11 and 12 months of age. However, synthesis rates from 4 months to 12 months increased (P[lt ] .03) in BF infants and decreased in both RF+cholesterol (P[lt ] .0001) and RF (P[lt ] .0001) fed groups. These results demonstrate relative insensitivity of synthesis rates and serum cholesterol concentrations to cholesterol challenge, irrespective of early dietary cholesterol intake in formula-fed and BF infants. These findings support the notion that early dietary cholesterol causes minimal changes in cholesterol metabolism about 6 months after dietary exposure in young infants.