PLASMA-CHOLESTEROL SYNTHESIS USING DEUTERATED WATER IN HUMANS - EFFECT OF SHORT-TERM FOOD RESTRICTION

  • 1 June 1988
    • journal article
    • research article
    • Vol. 111  (6) , 627-633
Abstract
Our purpose was to develop methods in humans to determine the fractional synthetic rate (FSR) of plasma pool free cholesterol using the rate of deuterium incorporation from body water. The sensitivity of this method was examined by measuring FSR after periods of fasting and feeding. Five healthy men with normal lipoprotein levels were given a prepared diet containing 40% of calories as fat and a polyunsaturated/saturated fatty acid ratio of 0.25 for 8 days, except for day 7 when they were given only drinking water. Beginning after the supper meal on day 6, they received no food until 8 AM on day 8 when they consumed meals as normal. Over days 7 and 8 the subjects were given prime and constant deuterium oxide daily orally to maintain body water deuterium enrichment at about 0.05 atom % excess. Plasma samples were obtained at 0 hours (day 7, 8 AM) and at 12, 24, 36, and 48 hours thereafter. Free cholesterol was extracted, purified by thin-layer chromatography, and combusted to water. The water was reduced to H2 and analyzed for deuterium enrichment by isotope ratio mass spectrometry. Analytic precision of this system was determined as 3.5.permill.(parts per mil) vs Standard Mean Ocean Water. Deuterium enrichment of plasma water for the group during the 48-hour deuterium oxide administration period was 3143 .permill. .+-. 310 .permill. (mean .+-. SEM). Cholesterol deuterium enrichment for the group during the 12-hour period of fasting (10.9 .permill. .+-. 4.1 .permill.) was not different from that during feeding (14.2 .permill. .+-. 6.2 .permill.). Cholesterol deuterium enrichment for the group after the period of fasting (2.0 .permill. .+-. 4.3 .permill.) was lower (p < 0.001) than that after feeding (38.7 .permill. .+-. 4.5 .permill.). After periods of fasting and feeding, FSR was calculated as precursor incorporation of deuterium into cholesterol by using a deuterium/carbon incorporation ratio of 0.81. FSR during 12-hour nocturnal periods after fasting (0.004 .+-. 0.006/day) was lower (p < 0.001) than during periods after feeding (0.052 .+-. 0.005/day). These results suggest that regulation of human plasma cholesterol synthesis is sensitive to short-term food restriction.