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We tested the hypothesis that aging affects whole-body protein turnover via altered fat-free mass (FFM). Whole-body protein kinetics were estimated by the 60-h oral [[sup.15]N]glycine method. Results from 16 healthy, elderly subjects (8 men and 8 women with a mean age of 72.6 y) were compared for age and sex effects with those of 15 lean young subjects (8 men and 7 women with a mean age of 28.4 y) during isoenergetic formula diets. Per kilogram body weight, nitrogen flux was lower only as an effect of age (P = 0.006) whereas age and female sex significantly lowered synthesis and breakdown (P [is less than or equal to] 0.04). However, per kilogram FFM, no significant age or sex effects on rates of protein kinetics remained. Age and female sex contributed significantly to decreased muscle protein catabolism (based on 3-methylhistidine excretion), both in absolute terms and as a percentage of whole-body protein breakdown in the elderly compared with the young: 20.2% compared with 30.9% in women and 27.9% compared with 39.8% in men. No significant age or sex effects on rates of nonmuscle lean tissue protein breakdown were observed with or without correction for body composition. We conclude that the lower rates of flux, synthesis, and breakdown per kilogram body weight in elderly compared with young persons are due to changes in body composition with aging because rates are not different per kilogram FFM. However, there is a reduced contribution by muscle to whole-body protein catabolism in older persons. This has potential implications for the nutrition of both normal and sick elderly persons.

Biosynthesis of cholesterol represents a major input into whole-body pools; however, its regulation has been difficult to study in humans because of limitations in methodologies. The present objectives are to compare available techniques for measuring this process and examine how dietary factors alter human cholesterol biosynthesis. Review of existing techniques suggests that mass isotopomer distribution analysis and deuterium incorporation approaches offer advantages over other methods. Dietary factors influencing human cholesterol synthesis include energy restriction, meal frequency, dietary fat type, and cholesterol and phytosterol content. Food deprivation for as short as 24 h results in almost complete cessation of cholesterol biosynthesis. Similarly, increased meal frequency patterns are associated with a substantial depression in synthesis. In contrast, consumption of oils rich in polyunsaturated fatty acids, despite reducing circulating concentrations, increases the cholesterol synthesis rate compared with other fats. Stepwise addition of dietary cholesterol is associated with only a modest decline in cholesterogenesis while raising plasma concentrations slightly. It can be concluded that synthesis, as a contributor to circulating cholesterol concentrations, is sensitive to many dietary factors. Energy deprivation results in the greatest decline in synthesis, likely accounting for the beneficial decline in circulating cholesterol concentrations observed with weight loss. Am J Clin Nutr 1997;66:438-46.

To assess the influence of dietary fat composition on rates of oxidation of dietary myristic (MA) and palmitic (PA) acids, eight healthy males consumed prepared solid-food diets for 11 d with 40% of total energy as fat. Fifty-five percent of the energy obtained in the form of fat was provided as butter or beef tallow. On days 8 and 11 of each diet cycle, 20 mg/kg body wt of either [[1.sup.-13] C]MA or [[1.sup.-13]C]PA was ingested with breakfast. Hourly breath samples were collected over 9 h thereafter and [sup.13][CO.sub.2] enrichments were determined by using isotope-ratio mass spectrometry. The percentage of [sup.13]C]MA appearing in breath carbon dioxide over 9 h was more than twofold that of PA (P

To examine meal-frequency effects on circulating hormone concentrations and cholesterol synthesis, male subjects consumed liquid diets given as either six evenly spaced (ES) or three diurnal (DI) meals over 3 d. Deuterium oxide was given on day 2 and blood sampled every 4 h over days 2 and 3 to measure plasma cholesterol, glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) concentrations and cholesterol synthesis. Cholesterol synthesis was determined from deuterium incorporation into plasma free cholesterol by using constrained and unconstrained curve-fit models. Plasma total cholesterol concentrations decreased in both ES and DI groups (P < 0.05). The ES group had lower insulin (P < 0.05) and GIP (P < 0.001) concentrations compared with the DI group. Cholesterol synthesis was reduced (P < 0.01) in the ES vs the DI group when determined by using constrained (0.050 [+ or -] 0.002 vs 0.075 [+ or -] 0.005 pools/d, respectively) and unconstrained (0.072 [+ or -] 0.005 vs 0.119 [+ or -] 0.011 pools/d, respectively) models. These data suggest meal frequency-dependent control of cholestero-genesis via hormonally mediated mechanisms.

Manufactured infant formulas have a much lower cholesterol content than breast milk. Cholesterol is required for many body functions, including maintenance of the membranes that surround every cell. Levels of dietary cholesterol may affect intestinal cholesterol production; the intestines, as well as the liver, have the ability to make cholesterol. The effect of differing levels of dietary cholesterol on cholesterol production by the liver and intestines was investigated in newborn piglets. The physiology of pigs closely resembles that of humans in crucial areas. In all piglets, plasma (blood) cholesterol levels rose with age, but plasma cholesterol levels were higher in breast milk (BM)-fed animals on days 15 and 25 postpartum than in formula-fed animals. In animals fed formula, cholesterol synthesis by the liver increased as a response to their low cholesterol diet, while intestinal cholesterol synthesis was not affected. The cholesterol synthesis in the livers of BM-fed animals was low, presumably because their diets supplied more cholesterol. In addition, cholesterol contained in intestinal cells was depleted following birth, probably for use in making bile acids and other important body compounds. The results indicate that in newborn piglets, liver cholesterol production can compensate for low cholesterol levels in the diet. (Consumer Summary produced by Reliance Medical Information, Inc.)