Use of deuterated water for measurement of short-term cholesterol synthesis in humans.

Previous methods for measurement of cholesterol synthesis de novo in humans have either required extended measurement periods or been indirect. Recently, a technique based on the rate of incorporation of deuterium from D2O into the plasma cholesterol pool has been developed. Following oral ingestion of D2O, deuterium enrichment over time in free plasma cholesterol after combustion and reduction was determined using isotope ratio mass spectrometry. This methodology enabled direct measurement of plasma cholesterol synthesis over intervals as short as 4 h. The technique has been used to demonstrate changes in synthetic rate in response to feeding conditions and genetic influences. Fasting over 36 h resulted in markedly reduced deuterium uptake into cholesterol in healthy males. Diurnal variations in synthetic rate have also been identified, with elevated synthesis observed during nocturnal periods in both fed and fasted subjects. In addition, the influence of apolipoprotein E phenotype on cholesterol synthesis has been shown using this technique. Individuals carrying the apoprotein epsilon 2 allele demonstrated lower synthesis compared with those possessing the epsilon 4 allele. Thus, the deuterium incorporation technique for measuring cholesterol synthesis demonstrates potential as a valuable stable isotope method for human nutrition studies.