EXISTENCE OF CONSISTENT HYPO- AND HYPERRESPONDERS TO DIETARY CHOLESTEROL IN MAN1

Abstract

Hyper- and hyporesponsiveness of serum cholesterol to dietary cholesterol is an established concept in animals but not in man. The authors studied the stability of the individual response of serum cholesterol to dietary cholesterol in three controlled experiments in 1982. The subjects were volunteers from the general population living in or near Wageningen, the Netherlands. Each experiment had a low-cholesterol baseline period (121, 106, and 129 mg/day in experiments 1, 2, and 3, respectively) and a high-cholesterol test period (625, 673, and 989 mg/day). Duplicate portion analysis showed that dietary cholesterol was the only variable. The 94 healthy men and women who completed experiment 1 showed an increase (mean ± standard deviation (SD)) in serum cholesterol of 0.50 ± 0.39 mmol/liter (19 ± 15 mg/dl). Seventeen putative hyperresponders, defined by their response in experiment 1, were retested in experiments 2 and 3; they showed responses of 0.28 ± 0.38 mmol/liter (11 ± 15 mg/dl) and 0.82 ± 0.35 mmol/liter (32 ± 14 mg/dl), respectively. Fifteen hyporesponders, selected in experiment 1, showed responses in experiments 2 and 3 of 0.06 ± 0.35 mmol/liter (2 ± 14 mg/dl) and 0.47 ± 0.26 mmol/liter (18 ± 10 mg/dl), significantly lower than the corresponding values for hyperresponders. The standardized regression coefficient for individual responses in experiment 2 on those in experiment 1 was β = 0.34 (p = 0.03, n = 32); the corresponding regression coefficient for experiment 3 and experiment 1 was 0.53 (p < 0.01). After correction for intraindividual fluctuations the true responsiveness distribution was found to have a between-subject standard deviation of about 0.29 mmol/liter (11 mg/dl). This implies that if the mean response to a certain dietary cholesterol load amounts to e.g., 0.58 mmol/liter (22 mg/dl), then the 16% of subjects least susceptible to diet will experience a rise of only 0.29 mmol/liter (11 mg/dl) or less, while in the 16% of subjects most susceptible to diet, serum cholesterol will rise by 0.87 mmol/liter (34 mg/dl) or more. The authors conclude that modest differences in responsiveness of serum cholesterol to dietary cholesterol do exist in man, and that the wide scatter of responses observed in single experiments is largely due to chance fluctuations.