Dietary cholesterol in graded amounts : threshold to ceiling effects upon plasma free cholesterol synthesis, equilibration and circulation levels in humans

The purpose of this study was to investigate the effect of dietary cholesterol upon plasma cholesterol concentration and cholesterogenesis; and the aspect of equilibration of newly synthesized cholesterol between plasma and red blood cell (RBC) in humans. Eight healthy subjects (seven men and one woman) at the age of 55.5 ± 4.2 (mean ± SEM) years were recruited for this study. Three experimental diets (55% carbohydrate, 15%protein, 30% fat, P:S = 0.8) containing 50mg (low), 350mg (medium) and 650mg (high) cholesterol per day were randomly consumed by these subjects for four weeks at levels designed to maintain body weight. On day 28 of each diet, subjects were given a priming dose of 0.7 g deuterium oxide(D20)/kg body water followed by maintenance doses over 24 hours. Cholesterol synthesis was determined as the fractional synthetic rate (FSR)of the rapid exchangeable pool calculated by deuterium incorporation from body water into plasma free cholesterol over 24 hours. RBC cholesterol deuterium incorporation was also compared to that of plasma free cholesterol. Plasma cholesterol was significantly elevated by 13% (+26mg/di, P = 0.002) in the high as compared to low but not medium cholesterol containing diets. Equilibration of deuterium enrichment from the newly synthesized plasma free cholesterol, expressed as parts per thousand (0/00) relative to Standard Mean Ocean Water (SMOW), to RBC cholesterol was significantly delayed over the initial 6 (51.7 ± 15.5 vs 1.8 ± 10.2/a, oof P = 0.010) and 12 (60.0 ± 12.3 vs 16.1 ± 8.0^oof P = 0.005) hours post dose in the high cholesterol diet. Dietary cholesterol levels of 50, 350, and 650 mg/day did not alter FSR (0.078 ± 0.016, 0.072 ± 0.007 and 0.071 ±0.014 day-1, respectively, P = 0.913). No relationship between change of plasma cholesterol and rate of cholesterogenesis was observed among the three experimental diets. These findings suggest that dietary cholesterol levels affect plasma cholesterol concentrations. Deuterium incorporation between plasma free cholesterol and RBC cholesterol is delayed over the initial 12 hours post dose. Use of a deuterium incorporation period of 24 hours, or more, enables more accurate determination of cholesterogenesis when using this methodology. Cholesterogenesis is neither affected by dietary cholesterol nor correlated with alterations of plasma cholesterol concentration.Land and Food Systems, Faculty ofGraduat