Cholesterol absorption, elimination, and synthesis related to LDL kinetics during varying fat intake in men with different apoprotein E phenotypes

Abstract

Cholesterol absorption, fecal elimination, and synthesis and low density lipoprotein (LDL) metabolism were measured in 29 middle-aged men while on their normal diet and a diet low in fat and cholesterol, and the obtained values were related to apoprotein (apo) E phenotypes. Basal cholesterol absorption efficiency was positively related to production rate (PR) for LDL apo B and negatively to cholesterol synthesis (measured by fecal steroids and dietary cholesterol), which in turn was negatively associated with the LDL level and positively with the fractional removal (FCR) of LDL apo B. The apo E subscript (e.g., E2/2=l, E2/3=2, etc.) was positively associated with cholesterol absorption and the LDL apo B and cholesterol levels and negatively with cholesterol synthesis and FCR for LDL apo B. Effective bile acid and cholesterol syntheses, fecal elimination of cholesterol, removal of LDL apo B, and low cholesterol absorption characterized men with the ε2 allele. Reduction of dietary fat and cholesterol intakes lowered LDL cholesterol levels and cholesterol absorption but increased cholesterol synthesis proportionally to the apo E subscript; the FCR and PR for LDL apo B were significantly increased and decreased, respectively. The decrease in absorption was related to enhanced removal of LDL apo B and synthesis of cholesterol. During the modified diet, cholesterol metabolism was poorly related to LDL, apo E phenotypes, and LDL apo B kinetics. A positive correlation of cholesterol absorption with dietary fat intake in combined studies suggests that a dietary fat reduction-associated decrease in LDL cholesterol is at least partly caused by reduced cholesterol absorption. The findings suggest that a moderately high LDL cholesterol level, frequently associated with the ε4 allele, appears to be associated with high cholesterol absorption and production of LDL apo B, low synthesis of bile acids and cholesterol, and removal of LDL apo B. Subjects with the ε4 allele show the greatest changes in their LDL cholesterol concentrations in response to a reduction of dietary fat and cholesterol.