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 beta = 0.34 (p = 0.03, n = 32); the corresponding regression coefficient for experiment 3 and experiment 1 was 0.53 (p less than 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.

Genetic Variation at the ApoA-IV Gene Locus and Response to Diet in Familial Hypercholesterolemia

“…[23][24][25] The range of the response to changes in the amount or type of dietary fat and cholesterol varies among individuals. [35][36][37] As a group, our FH subjects (Table 2) responded to the NCEP-I diet with 15% and 17% reductions in total cholesterol and LDL-C, respectively, in agreement with what has been previously reported. 26 ApoA-I, apoB, and apoE are among the genetic loci that have been implicated in the variable lipidic response to dietary changes.…”

Influence of apolipoprotein A‐1 promoter polymorphism on lipid levels and responses to dietary change in Finnish adults

“…Diet studies have demonstrated that some individuals are consistent hypo-and hyperresponders to dietary cholesterol [37], although these different responses cannot be predicted. To date, only two dietary studies have been carried out to determine the association between apo A-1 promoter genotype and plasma lipid responses to dietary change [15,23].…”

The response of lipoproteins to dietary fat and cholesterol in lean and obese persons

“…However, when we repeated this trial 6 years later in the same volunteers with the same challenge and design [18], the correlation between an individual's response in the first and in the second study was only r = 0.32: many of the putative hyperresponders had become hyporesponders, and vice versa. The same was true for other cohorts of volunteers whom we tested repeatedly over the years [19][20][21][22]. Keys and coworkers [23], who studied one group of men on a variety of diets, also concluded that true non-responsiveness is rare if it exists at all, even though one subject may react aberrantly in one particular trial.…”