Cholesterol absorption efficiency declines at moderate dietary doses in normal human subjects.

While unphysiologically large cholesterol doses are known to reduce percent cholesterol absorption, smaller amounts are reported to have no effect in human subjects. To determine the dose;-response relation between dietary cholesterol consumed and the efficiency of intestinal cholesterol absorption, we fed 18 normal subjects two test meals containing different amounts of natural cholesterol. In each test pentadeuterated cholesterol tracer was given orally, hexadeuterated cholesterol tracer was given intravenously, and the tracer ratio was measured in plasma 4 days later by gas chromatography/negative ion mass spectrometry. Baseline cholesterol absorption in the presence of 26 mg cholesterol tracer was 40.7 +/- 2.3%. This decreased by 4.9 percentage points (P = 0.05) when a total of 188 mg cholesterol was included in the meal and by 15.6 percentage points (P = 0.006) when 421 mg cholesterol was given, showing that the efficiency of cholesterol absorption declines appreciably even with modest increases in cholesterol dose. Considerable variation was noted in the response of different subjects and, on the higher cholesterol dose, dietary cholesterol absorption varied 5-fold from 40 mg to 212 mg. Fasting plasma insulin was correlated with the ability to absorb higher cholesterol doses without loss of efficiency (r(s) = 0.700, P = 0.036). Percent cholesterol absorption in a single meal is significantly influenced by the amount of cholesterol in that meal, suggesting that acute dietary factors influencing cholesterol absorption need further study.