Effect of meal timing on diurnal rhythm of human cholesterol synthesis

Abstract

To test whether the diurnal rhythm of cholesterol synthesis in humans is entrained to meal timing, the effect of a 6.5-h delay of mealtimes was investigated in four normal lipidemic male subjects. Cholesterol fractional synthetic rate was measured by deuterium incorporation from body water using blood sampling every 2 h. The baseline was a 24-h control period in which three Western-style meals were consumed at 0700, 1150, and 1640, followed by 3 days in which meals were delayed by 6.5 h, i.e., meals consumed at 1330, 1820, and 2310 without changing the sleep-wake and light-dark cycles. Cholesterol synthesis was maximal at 2200 +/- 0200 and minimal at 1130 +/- 0050 on the baseline day. On day 1 of the shifted meals, the maximum was delayed 6.0 +/- 0.5 h and the nadir was not changed. On day 3, the maximum was delayed 8.6 +/- 3.7 h and the minimum was delayed 6.5 +/- 2.4 h from baseline. The mean amplitude of the cholesterol rhythm was significantly greater on day 3,233 +/- 35%, compared with baseline which was 109 +/- 15%. A strong negative correlation (r = -0.66 +/- 0.10) was found between the rhythms of cholesterol synthesis and cortisol during the baseline day, but there was a phase delay in the rhythm of cholesterol synthesis relative to cortisol on day 1 and day 3. Findings indicate that the 24-h variation in cholesterol synthesis is strongly dependent on meal timing.