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Deuterium uptake and plasma cholesterol precursor levels correspond as methods for measurement of endogenous cholesterol synthesis in hypercholesterolemic women

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Lipids

Abstract

To assess the validity of two techniques used to measure human cholesterol synthesis, the rate of uptake of deuterium (D) into plasma free cholesterol (FC), and plasma cholesterol precursor (squalene, lanosterol, desmosterol and lathosterol) levels were compared in 14 women [65–71 yr with low density lipoprotein-cholesterol (LDL-C)≥3.36 mmol·l −1]. Subjects consumed each of six diets for 5-wk periods according to a randomized crossover design. The experimental diets included a baseline diet (39% energy as fat, 164 mg chol·4.2 MJ−1) and five reduced-fat diets (30% of energy as fat), where two-thirds of the fat was either soybean oil; squeeze, tub or stick margarines; or butter. Fractional and absolute synthesis rates (FSR and ASR) of FC were determined using the deuterium incorporation (DI) method, while cholesterol precursor levels were measured using gas-liquid chromatography. Data were pooled across diets for each variable and correlation coefficients were calculated to determine if associations were present. There was good agreement among levels of the various cholesterol precursors. In addition, FSR in pools/d (p·d−1) and ASR in grams/d (g·d−1) were strongly associated with lathosterol (r=0.72 and 0.71, P=0.0001), desmosterol (r=0.75 and 0.75, P=0.0001), lanosterol (r=0.67 and 0.67), and squalene (r=0.69 and 0.68) when levels of the precursors were expressed as μmol·mmol−1C. Significant but lower correlations were observed between the D uptake and plasma cholesterol precursor levels when the latter were expressed in absolute amounts (μmol·L−1). The wide range of fatty acid profiles of the experimental diets did not influence the degree of association between methods. In conclusion, the DI method and levels of some cholesterol precursors correspond as methods for shortterm measurement of cholesterol synthesis.

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Abbreviations

ASR:

absolute synthesis rate

C:

cholesterol

CVD:

cardiovascular disease

D:

deuterium

DI:

deuterium incorporation

Dmax :

maximum number of deuterium molecules

FC:

free cholesterol

FSR:

fractional synthesis rate

HMG-CoA:

3-hydroxyl-3-methylglutaryl coenzyme A

MIDA:

mass isotopomer distribution analyses

TC:

total cholesterol

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Authors and Affiliations

  1. Jean Mayer USDA Human Nutrition Center on Aging at Tufts University, 02111, Boston, Massachusetts

    Alice H. Lichtenstein & Lynne M. Ausman

  2. School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Macdonald Campus, 21,111 Lakeshore Road, H9X 3V9, Ste-Annede-Bellevue, Québec, Canada

    Nirupa R. Matthan, Mahmoud Raeini-Sarjaz & Peter J. H. Jones

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  1. Nirupa R. Matthan
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  2. Mahmoud Raeini-Sarjaz
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  3. Alice H. Lichtenstein
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Correspondence to Peter J. H. Jones.

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Matthan, N.R., Raeini-Sarjaz, M., Lichtenstein, A.H. et al. Deuterium uptake and plasma cholesterol precursor levels correspond as methods for measurement of endogenous cholesterol synthesis in hypercholesterolemic women. Lipids 35, 1037–1044 (2000). https://doi.org/10.1007/s11745-000-0616-9

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  • DOI: https://doi.org/10.1007/s11745-000-0616-9

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