Plasma levels of lathosterol and phytosterols in relation to age, sex, anthropometric parameters, plasma lipids, and apolipoprotein E phenotype, in 160 Dutch families

In this study, the relation of plasma levels of lathosterol (an indicator of whole body cholesterol synthesis) and plant sterols (indicator of cholesterol absorption) with age, sex, weight, height, plasma lipids, and lipoproteins, and with apolipoprotein (apo) E phenotype, was investigated in a group of 160 nuclear families consisting of twins living with their parents. Lathosterol was higher in fathers than in mothers, but not different between boys and girls. In each of these four groups, there was a strong correlation with plasma and low-density lipoprotein (LDL)-cholesterol and -triglyceride, as well as with body weight, but not with height or high-density lipoprotein (HDL)-cholesterol. In adults, lathosterol was inversely correlated with plant sterols. Lathosterol was higher in children with E4/3 phenotype than in those with E3/3 or E3/2; in adults, lathosterol did not differ among the various E phenotypes. The plasma levels of the two plant sterols, campesterol and (+sitosterol, were highly correlated with each other, and also with plasma or LDL-cholesterol, in each of the four groups. Plant sterols were higher in adults or children with E4/3 phenotype as compared with those with other phenotypes. In multivariate analysis (performed separately for two groups of adults and children) plasma cholesterol, plasma plant sterols, plasma triglycerides, and weight were found to make significant contributions to the variation of lathosterol in all groups, and E phenotype and sex only in one group, while age did not contribute in any group. For plant sterols, plasma cholesterol and lathosterol were significant independent predictors in all groups, sex and E phenotype only in one or two of the four groups, and age, weight, height, and HDL-cholesterol in none of the groups. Thus, although lathosterol and plant sterols were weakly related to E phenotype in some of the groups, these findings do not support a major role for the E phenotype in determining rates of cholesterol synthesis or absorption, as claimed by others. Copyright o 1991 by W.B. Saunders Company T HE RATES OF cholesterol synthesis and cholesterol absorption in man are of considerable interest in both fundamental and clinical respects. The latter has been underscored in recent years by the advent of potent and selective inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, rate-limiting for the overall process of cholesterol synthesis.‘,’ These inhibitors have proven to be capable of lowering serum levels of low-density lipoprotein (LDL) with minimal side effects,’ and have found wide acceptance already for the treatment of severe hypercholesterolemia. In 1988, we reported on the use of the serum concentration of lathosterol, a late precursor of cholesterol, as an indicator of the rate of whole body cholesterol synthesis in healthy males on normal western diets.4 In that report, we confirmed the pioneering work of Miettinen et al,5-7 showing that serum levels of lathosterol and other sterol precursors changed in the same direction as the (expected) rate of cholesterol synthesis upon various manipulations, including small intestinal resection, cholestyramine feeding, or bile acid administration. Additional support for the validity of serum lathosterol as indicator for whole body cholesterol synthesis was gained from the demonstration that serum lathosterol was strongly decreased (more than serum LDL)