Regulation of cholesterol biosynthesis by diet in humans

Biosynthesis of cholesterol represents a major input into whole-body pools; however, its regulation has been difficult to study in humans because of limitations in methodologies. The present objectives are to compare available techniques for measuring this process and examine how dietary factors alter human cholesterol biosynthesis. Review of existing techniques suggests that mass isotopomer distribution analysis and deuterium incorporation approaches offer advantages over other methods. Dietary factors influencing human cholesterol synthesis include energy restriction, meal frequency, dietary fat type, and cholesterol and phytosterol content. Food deprivation for as short as 24 h results in almost complete cessation of cholesterol biosynthesis. Similarly, increased meal frequency patterns are associated with a substantial depression in synthesis. In contrast, consumption of oils rich in polyunsaturated fatty acids, despite reducing circulating concentrations, increases the cholesterol synthesis rate compared with other fats. Stepwise addition of dietary cholesterol is associated with only a modest decline in cholesterogenesis while raising plasma concentrations slightly. It can be concluded that synthesis, as a contributor to circulating cholesterol concentrations, is sensitive to many dietary factors. Energy deprivation results in the greatest decline in synthesis, likely accounting for the beneficial decline in circulating cholesterol concentrations observed with weight loss.