Evidence for diurnal periodicity in human cholesterol synthesis

Diurnal variation in human cholesterol synthesis in the rapidly exchangeable pool was studied in six healthy normolipidemic individuals by measurement of deuterium incorporation from body water into plasma cholesterol. After oral administration of D2O, free and de-esterified plasma cholesterol and plasma water were sampled over 48 h, converted to hydrogen, and deuterium enrichment was determined by isotope ratio mass spectrometry. Deuterium enrichment changes over 4-h intervals were used to calculate fractional synthetic rate (FSR). No significant time effects were observed on plasma total cholesterol levels over the 48-h study. The highest rate of deuterium incorporation into free cholesterol occurred during early morning, whereas during afternoon and early evening incorporation rates were lower. Free cholesterol FSR values were lowest at 14:00 to 18:00 h and peaked at 06:00 h. The periodicity across timepoints was not significantly different from that of a derived sine function equation. For cholesteryl ester, FSR data showed less distinct variation over time, peaking during early morning, indicative of maximal efflux of free cholesterol to the ester pool during this period. These findings offer direct evidence for diurnal patterns in human cholesterol synthesis.