Serum Low Density Lipoprotein Cholesterol Concentration Is Not Dependent on Cholesterol Synthesis and Absorption in Healthy Humans

Introduction. Pharmacological reduction of cholesterol (C) synthesis and C absorption lowers serum low-density lipoprotein C (LDL-C) concentrations. We questioned whether high baseline C synthesis or C absorption translates into high serum LDL-C concentrations or if there was no connection. Therefore, we studied the association between serum LDL-C and C synthesis or C absorption in healthy subjects. Methods. Three published data sets of young subjects on different diets (study 1), mildly hypercholesterolemic subjects without cardiovascular disease (study 2) and healthy controls of the Framingham study (study 3) were used. The three study populations varied in sex, age, and weight. C synthesis and C fractional absorption rate (FAR) were measured with fecal sterol balance and stable isotope techniques (studies 1 and 2). Additionally, serum lathosterol and campesterol concentrations corrected for the serum total C concentration (R_lathosterol and R_campesterol) were used as markers for hepatic C synthesis and C FAR, respectively (studies 1–3). Linear regression analysis was applied to evaluate associations between LDL-C, C synthesis, and C absorption. Results. Seventy-three, 37, and 175 subjects were included in studies 1, 2, and 3, respectively. No statistically significant associations were found between LDL-C and the measured C synthesis and C FAR, nor for R_lathosterol and R_campesterol in any of the study groups. This lack of associations was confirmed by comparing the male subjects of studies 1 and 2. Study 1 subjects had a 50% lower serum LDL-C than the study 2 subjects (p < 0.01), but not a lower C synthesis, C FAR, R-lathosterol, or R_campesterol. Conclusions. Under physiological conditions, C synthesis and C FAR are not major determinants of circulating serum LDL-C concentrations in healthy subjects. The results need to be confirmed in large-scale studies in healthy subjects and patients at risk for cardiovascular disease.