Effects of early cholesterol intake on cholesterol biosynthesis and plasma lipids among infants until 18 months of age.

BACKGROUND: The endogenous cholesterol fractional synthesis rate (FSR) is related inversely to infant dietary cholesterol at 4 months of age; however, it remains to be established whether this effect is permanent, possibly contributing to later hypercholesterolemia. OBJECTIVE: To determine whether levels of dietary cholesterol in infancy induced changes in FSR and plasma lipid levels that persisted at 18 months. METHODS: A prospective clinical trial was conducted with 47 infants, from their first week of life until 18 months of age, who received human milk (HM) until weaned (n = 15) or were randomized to receive modified cow's milk formula (MCF) with added cholesterol (n = 15) or cow's milk formula (CF) (n = 17) for 12 months. Cholesterol contents of HM, MCF, and CF were 120, 80, and 40 mg/L, respectively. FSR and plasma lipid levels were measured at 4 and 18 months. RESULTS: At 4 months, total cholesterol and low-density lipoprotein cholesterol levels were higher for infants fed HM and MCF, compared with CF. High-density lipoprotein cholesterol levels were higher in the MCF group than in the HM and CF groups. FSR in the HM group (0.034 +/- 0.005 pools per day) was lower than that in the CF group (0.052 +/- 0.005 pools per day). There was no difference between the HM and MCF (0.047 +/- 0.005 pools per day) groups or between the MCF and CF groups. At 18 months, there were no differences in FSRs or plasma lipid profiles between the groups. CONCLUSION: Although cholesterol intake before weaning affects FSRs and plasma lipid profiles at 4 months, these differences do not persist after weaning to an unrestricted diet at 18 months. This provides additional evidence that there is no imprinting of FSR in infancy with differing dietary levels of cholesterol.

Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes.

The pharmacokinetics of isoflavones in 10 healthy women were determined from serum appearance/disappearance concentration profiles and urinary excretions after single-bolus ingestion of 10, 20 or 40 g of soy nuts delivering increasing amounts of the conjugated forms of daidzein (6.6, 13.2 and 26.4 mg) and genistein (9.8, 19.6 and 39.2 mg). Peak serum daidzein and genistein concentrations were attained after 4-8 h, and elimination half-lives were 8.0 and 10.1 h, respectively. There were no differences in the pharmacokinetics of daidzein and genistein between pre- and postmenopausal women, indicating absorption and disposition of isoflavones to be independent of age or menopausal status. A curvilinear relationship was observed between the bioavailability of daidzein and genistein, apparent from the area under the curve to infinity (AUC(inf)) of the serum concentration-time profiles and the amount of isoflavones ingested. The mean fraction of the isoflavones excreted in urine decreased with increasing intake when expressed as a percentage of the administered dose (63.2 +/- 8.0, 54.4 +/- 8.1 and 44.0 +/- 4.3%, respectively, for daidzein, and correspondingly, 25.2 +/- 5.3, 13.4 +/- 2.1 and 15.8 +/- 2.7% for genistein), underscoring the trend toward nonlinear pharmacokinetics. Equol was identified as a metabolite in 30% of women; it was present consistently in urine and blood from the same subjects. Its delayed appearance was consistent with colonic synthesis. On the basis of the pharmacokinetics, optimum steady-state serum isoflavone concentrations would be expected from modest intakes of soy foods consumed regularly throughout the day rather than from a single highly enriched product.

Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease.

OBJECTIVE: To determine whether tauroursodeoxycholic acid (TUDCA) would prevent or ameliorate the liver injury in neonates treated with total parenteral nutrition (TPN). STUDY DESIGN: Eligible infants were enrolled after surgery when serum direct bilirubin (DB) was <2 mg/dL. TUDCA (30 mg/kg/day) was given enterally to 22 subjects. A concurrent untreated/placebo group was evaluated for comparison (n = 30). Blood chemistries including alanine aminotransferase (ALT), alkaline phosphatase (AP), conjugated bilirubin (CB), and bile acids (BA) were obtained weekly. RESULTS: There was no difference in peak serum CB, ALT, AP, or BA levels between the TUDCA-treated and control infants. When stratified for birth weight (<1500 g and >1500 g), no differences in peak CB, ALT, AP, or BA were noted. Serum CB levels were similar between TUDCA-treated and control infants after 14, 40, 60, 70, and 120 days of TPN. CONCLUSION: TUDCA appears ineffective in preventing the development or treatment of TPN-associated cholestasis in neonates. Erratic biliary enrichment and prolonged inability to initiate treatment may compromise the utility of enterically administered TUDCA for TPN-treated infants.