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Research Article| Volume 29, ISSUE 9, P1149-1155, September 1988

Serum lathosterol concentration is an indicator of whole-body cholesterol synthesis in humans.

Open AccessPublished:September 01, 1988DOI:https://doi.org/10.1016/S0022-2275(20)38456-X
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      The power of serum lathosterol concentration as an indicator of whole-body cholesterol synthesis was investigated in 47 human volunteers consuming two diets differing in fatty acid composition. The cholesterol balance (fecal excretion of neutral and acid steroids minus cholesterol intake) was strongly correlated with the serum level of total (free plus esterified) lathosterol and also with the ratio of serum lathosterol over serum cholesterol, both on a diet rich in polyunsaturated fatty acids (r = 0.74 for the ratio) and one containing mainly saturated fatty acids (r = 0.70 for the ratio). In a subgroup for which the serum levels of free lanosterol and other free methylsterols were also quantitated, the correlations of these levels (expressed relative to serum free cholesterol) with the cholesterol balance were lower than that found for total lathosterol (expressed relative to serum total cholesterol). A further corroboration was obtained by measuring the lathosterol/cholesterol ratio in 20 patients with familial hypercholesterolemia before and during treatment with the hydroxymethylglutaryl coenzyme A reductase inhibitor Mk-733. The ratio was lowered by 47% during drug treatment, suggesting a significant decrease of the cholesterol balance in these patients. We conclude, from the various indicators proposed to monitor whole-body cholesterol synthesis, that the lathosterol/cholesterol ratio in serum appears preferable with respect to indicative power and ease of quantitation.

      REFERENCES

        • Grundy S.M.
        • Ahrens Jr., E.H.
        • Miettinen T.A.
        Quantitative isolation and gas-liquid chromatographic analysis of total fecal bile acids.
        J. Lipid Res. 1965; 6: 397-410
        • Miettinen T.A.
        • Ahrens Jr., E.H.
        • Grundy S.M.
        Quantitative isolation and gas-liquid chromatographic analysis of total dietary and fecal neutral steroids.
        J. Lipid Res. 1965; 6: 411-424
        • Miettinen T.A.
        Detection of changes in human cholesterol metabolism.
        Ann. Clin. Res. 1970; 2: 300-320
        • Miettinen T.A.
        Diurnal variation of cholesterol precursors squalene and methyl sterols in human plasma lipoproteins.
        J. Lipid Res. 1982; 23: 466-473
        • Miettinen T.A.
        Cholesterol precursors and their diurnal rhythm in lipoproteins of patients with jejuno-ileal bypass and ileal dysfunction.
        Metabolism. 1985; 34: 425-430
        • Nestel P.J.
        • Kudchodkar B.
        Plasma squalene as an index of cholesterol synthesis.
        Clin. Sci. Mol. Med. 1975; 49: 621-624
        • Liu G.C.K.
        • Ahrens Jr., E.H.
        • Schreibman P.H.
        • Crouse J.R.
        Measurement of squalene in human tissues and plasma: validation and application.
        J. Lipid Res. 1976; 17: 38-45
        • Parker T.S.
        • McNamara D.J.
        • Brown C.
        • Garrigan O.
        • Kolb R.
        • Batwin H.
        • Ahrens Jr., E.H.
        Mevalonic acid in human plasma: relationship of concentration and circadian rhythm to cholesterol synthesis rates in man.
        Proc. Natl. Acad. Sci. USA. 1982; 79: 3037-3041
        • Parker T.S.
        • McNamara D.J.
        • Brown C.D.
        • et al.
        Plasma mevalonate as a measure of cholesterol synthesis in man.
        J. Clin. Invest. 1984; 74: 795-804
        • Miettinen T.A.
        Cholesterol and bile acid synthesis in two families with homozygous and heterozygous hypercholesterolemia.
        Arteriosclerosis. 1984; 4: 383-388
        • Saudek C.D.
        • Frier B.M.
        • Liu G.C.K.
        Plasma squalene: lipoprotein distribution and kinetic analysis.
        J. Lipid Res. 1978; 19: 827-835
        • Miettinen T.A.
        • Tilvis R.S.
        Comparison of the different components in the fractional conversion of mevalonate to cholesterol with cholesterol synthesis and serum methyl sterols.
        Scand. J. Clin. Lab. Invest. 1981; 41: 507-512
        • Miettinen T.A.
        Effects of bile acid feeding and depletion on plasma and biliary squalene, methyl sterols and lathosterol.
        in: Paumgartner G. Stiehl A. Gerok W. Bile Acids and Lipids. MTP Lancaster Press, London1981: 255-262
        • Vuoristo M.
        • Miettinen T.A.
        Serum cholesterol and precursor sterols in coeliac disease; effect of gluten-free diet and cholestyramine.
        Gut. 1986; 27: 1312-1319
        • Katan M.B.
        • Beynen A.C.
        • de Vries J.M.
        • Nobels A.
        Existence of consistent hypoand hyperresponders to dietary cholesterol in man.
        Am. J. Epidemiol. 1986; 123: 221-234
        • Katan M.B.
        • Beynen A.C.
        Characteristics of human hypoand hyperresponders to dietary cholesterol.
        Am. J. Epidemiol. 1987; 125: 387-399
        • Bronsgeest-Schoute D.C.
        • Hermus R.J.J.
        • Dallinga-Thie G.M.
        • Hautvast J.G.A.J.
        Dependence of the effects of dietary cholesterol and experimental conditions on serum lipids in man. III. The effect on serum cholesterol of removal of eggs from the diet of free-living, habitually egg-eating people.
        Am. J. Clin. Nutr. 1979; 32: 2193-2197
        • Beynen A.C.
        • Katan M.B.
        Reproducibility of the variations between humans in the response of serum cholesterol to cessation of egg consumption.
        Atherosclerosis. 1985; 57: 19-31
        • Beynen A.C.
        • Katan M.B.
        • van Gent C.M.
        Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol.
        Clin. Nutr. 1986; 5: 151-158
        • Brussaard J.H.
        • Katan M.B.
        • Hautvast J.G.A.J.
        Fecal excretion of bile acids and neutral steroids on diets differing in type and amount of dietary fat in young healthy persons.
        Eur. J. Clin. Invest. 1983; 13: 115-122
        • Moll M.J.T.M.
        • Erkelens D.W.
        • Gevers Leuven J.A.
        • Schouten J.A.
        • Stalenhoef A.F.H.
        Effects of synvinolin (MK-733) on plasma lipids in familial hypercholesterolemia.
        Lancet. 1986; 2: 936-938
      1. Moll, M. J. T. M., D. W. Erkelens, J. A. Gevers Leuven, J. A. Schouten, and A. F. H. Stalenhoef. 1988. MK-733: the most potent cholesterol synthesis inhibitor in familial hypercholesterolemia. Atherosclerosis. In press.

        • Jonker D.
        • van de Hoek G.D.
        • Glatz J.F.C.
        • Homan C.
        • Posthumus M.A.
        • Katan M.B.
        Combined determination of free, esterified and glycosylated plant sterols in foods.
        Nutr. Rep. Int. 1985; 32: 943-951
        • Glatz J.F.C.
        • Schouten F.J.M.
        • den Engelsman G.
        • Katan M.B.
        Quantitative determination of neutral steroids and bile acids in human feces by capillary gas-liquid chromatography.
        in: Beynen A.C. Geelen M.J. Katan M.B. Schouten J.A. Cholesterol Metabolism in Health and Disease: Studies in the Netherlands. Ponsen & Looijen, Wageningen, The Netherlands1985: 103-110
        • Abell L.L.
        • Levy B.B.
        • Brodie B.B.
        • Kendall F.E.
        A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity.
        J. Biol. Chem. 1952; 195: 357-366
        • Tilvis R.
        • Miettinen T.A.
        Squalene, methyl sterol and cholesterol levels in human organs.
        Arch. Pathol. Lab. Med. 1980; 104: 35-40
        • Folch J.
        • Lees M.
        • Sloane Stanley G.H.
        A simple method for the isolation and purification of total lipids from animal tissues.
        J. Biol. Chem. 1957; 226: 497-509
        • Snedecor G.W.
        • Cochran W.G.
        Statistical Methods. 6th Ed. Iowa State University Press, Ames, IA1967: 342-343
        • Nestel P.J.
        • Whyte H.M.
        • Goodman D.S.
        Distribution and turnover of cholesterol in humans.
        J. Clin. Invest. 1969; 48: 982-991
        • Brady D.R.
        • Gaylor J.L.
        Enzymic formation of esters of methyl sterol precursors of cholesterol.
        J. Lipid Res. 1971; 12: 270-276
        • Tiivis R.
        • Miettinen T.A.
        A lack of esterification of lanosterol and other methyl sterols in human serum in vitro.
        Scand. J. Clin. Lab. Invest. 1980; 40: 671-674
        • Sangvi A.
        • Galli G.
        • Scallen T.J.
        Coordinate regulation of cholesterol metabolism. Meeting Summary.
        Arteriosclerosis. 1985; 5: 303-309
        • Grundy S.M.
        • Ahrens Jr., E.H.
        • Davignon J.
        The interaction of cholesterol absorption and cholesterol synthesis in man.
        J. Lipid Res. 1969; 10: 304-315
        • Bhattacharyya A.K.
        • Connor W.E.
        • Spector A.A.
        Abnormalities of cholesterol turnover in hypercholesterolemic (Type II) patients.
        J. Lab. Clin. Med. 1976; 88: 202-214
        • Grundy S.M.
        • Bilheimer D.W.
        Inhibition of 3-hydroxy-3-methylglutaryl CoA reductase by mevinolin in familial hypercholesterolemia heterozygotes: effects on cholesterol balance.
        Proc. Natl. Acad. Sci. USA. 1984; 81: 2538-2542
        • Björkhem I.
        • Miettinen T.
        • Reihnér E.
        • Ewerth S.
        • Angelin B.
        • Einarsson K.
        Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reductase in human liver.
        J. Lipid Res. 1987; 28: 1137-1143