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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Review Article

Plasma Non-cholesterol Sterols as Markers of Cholesterol Synthesis and Intestinal Absorption: A Critical Review

Author(s): Eder Carlos Rocha Quintão*

Volume 26 , Issue 40 , 2020

Page: [5152 - 5162] Pages: 11

DOI: 10.2174/1381612826666200730220230

Price: $65


Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias and in population-based investigations to evaluate the risk for cardiovascular disease, respectively. The method aims at replacing initial research procedures such as the use of stable isotopes associated with fecal steroid balance, which are limited by the high cost and tedious procedures. However, we show in this review that numerous results obtained with serum sterol measurements are contradictory. In this regard, the following points are discussed: 1) how phytosterols relate to atherosclerosis considering that defects in biliary output or in the transport of phytosterols from the intestinal mucosa back into the intestinal lumen provide increased content of phytosterols and other sterols in plasma and tissues, thus not allowing to conclude that their presence in arteries and atheromas represents the etiology of atherosclerosis; 2) serum non-cholesterol sterols as markers of cholesterol synthesis and absorption, such as cholestanol, present discrepant results, rendering them often inadequate to identify cases of coronary artery disease as well as alterations in the whole body cholesterol metabolism; 3) such methods of measurement of cholesterol metabolism are confounded by factors like diabetes mellitus, body weight and other pathologies including considerable hereditary hyperlipidemias biological variabilities that influence the efficiency of synthesis and intestinal absorption of cholesterol.

Keywords: Cholesterol metabolism, phytosterols, cholesterol synthesis markers, cholestanol, coronary, hyperlipidemias.

Matthan NR, Resteghini N, Robertson M, et al. PROSPER Group. Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial. J Lipid Res 2010; 51(1): 202-9.
[] [PMID: 19578163]
Matthan NR, Pencina M, LaRocque JM, et al. Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD. J Lipid Res 2009; 50(9): 1927-35.
[] [PMID: 19436064]
Dayspring TD, Varvel SA, Ghaedi L, Thiselton DL, Bruton J, McConnell JP. Biomarkers of cholesterol homeostasis in a clinical laboratory database sample comprising 667,718 patients. J Clin Lipidol 2015; 9(6): 807-16.
[] [PMID: 26687702]
Gong Z, Qi Y, Zhao F, et al. Association between very low density lipoprotein cholesterol and cholesterol absorption/synthesis markers in patients with moderate and high risk of coronary heart disease. Zhonghua Xin Xue Guan Bing Za Zhi 2015; 43(11): 936-42.
[PMID: 26888803]
Gylling S, Plat J, Mensink RP, Baumgartner S. Non-cholesterol sterol concentrations as biomarkers for cholesterol absorption and synthesis in different metabolic disorders: a systematic review. Nutrients 2019; 11(1)
Weingärtner O, Lütjohann D, Meyer S, et al. Low serum lathosterol levels associate with fatal cardiovascular disease and excess all-cause mortality: a prospective cohort study. Clin Res Cardiol 2019; 108(12): 1381-5.
[] [PMID: 30949753]
Gylling H, Miettinen TA. Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment. Diabetologia 1994; 37(8): 773-80.
[] [PMID: 7988779]
Hoenig MR, Walker PJ, Gurnsey C, Beadle K, Johnson L. Markers of cholesterol absorption and synthesis predict the low-density lipoprotein cholesterol response to atorvastatin. J Cardiovasc Pharmacol 2010; 56(4): 396-401.
[] [PMID: 20625310]
Miettinen TA, Strandberg TE, Gylling H. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol. Arterioscler Thromb Vasc Biol 2000; 20(5): 1340-6.
[] [PMID: 10807752]
Hedman M, Miettinen TA, Gylling H, Ketomäki A, Antikainen M. Serum noncholesterol sterols in children with heterozygous familial hypercholesterolemia undergoing pravastatin therapy. J Pediatr 2006; 148(2): 241-6.
[] [PMID: 16492436]
Assmann G, Kannenberg F, Ramey DR, Musliner TA, Gutkin SW, Veltri EP. Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe-statin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia. Curr Med Res Opin 2008; 24(1): 249-59.
[] [PMID: 18053317]
Lakoski SG, Xu F, Vega GL, et al. Indices of cholesterol metabolism and relative responsiveness to ezetimibe and simvastatin. J Clin Endocrinol Metab 2010; 95(2): 800-9.
[] [PMID: 19965915]
Peach M, Xu R, Fitzpatrick D, et al. Effect of evolocumab on cholesterol synthesis and absorption. J Lipid Res 2016; 57(12): 2217-24.
[] [PMID: 27707817]
Raal FJ, Pappu AS, Illingworth DR, et al. Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia. Atherosclerosis 2000; 150(2): 421-8.
[] [PMID: 10856535]
Wu WF, Wang QH, Zhang T, Mi SH, Liu Y, Wang LY. Gas chromatography analysis of serum cholesterol synthesis and absorption markers used to predict the efficacy of simvastatin in patients with coronary heart disease. Clin Biochem 2013; 46(12): 993-8.
[] [PMID: 23598259]
Silbernagel G, Steiner LK, Hollstein T, et al. The interrelations between PCSK9 metabolism and cholesterol synthesis and absorption. J Lipid Res 2019; 60(1): 161-7.
[] [PMID: 30323110]
von Eckardstein A, Nofer JR, Assmann G. High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2001; 21(1): 13-27.
[] [PMID: 11145929]
Hoenig MR, Sellke FW. Insulin resistance is associated with increased cholesterol synthesis, decreased cholesterol absorption and enhanced lipid response to statin therapy. Atherosclerosis 2010; 211(1): 260-5.
[] [PMID: 20356594]
Descamps OS, De Sutter J, Guillaume M, Missault L. Where does the interplay between cholesterol absorption and synthesis in the context of statin and/or ezetimibe treatment stand today? Atherosclerosis 2011; 217(2): 308-21.
[] [PMID: 21762916]
Miettinen TA, Gylling H, Nissinen MJ. The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption. Nutr Metab Cardiovasc Dis 2011; 21(10): 765-9.
[] [PMID: 21899991]
Bombo RP, Afonso MS, Machado RM, et al. Dietary phytosterol does not accumulate in the arterial wall and prevents atherosclerosis of LDLr-KO mice. Atherosclerosis 2013; 231(2): 442-7.
[] [PMID: 24267264]
Nunes VS, Cazita PM, Catanozi S, Nakandakare ER, Quintão ECR. Phytosterol containing diet increases plasma and whole body concentration of phytosterols in apoE-KO but not in LDLR-KO mice. J Bioenerg Biomembr 2019; 51(2): 131-6.
[] [PMID: 30739226]
Miettinen TA. Serum squalene and methyl sterols as indicators of cholesterol synthesis in vivo. Life Sci 1969; 8(14): 713-21.
[] [PMID: 5801489]
Kempen HJ, Glatz JF, Gevers Leuven JA, van der Voort HA, Katan MB. Serum lathosterol concentration is an indicator of whole-body cholesterol synthesis in humans. J Lipid Res 1988; 29(9): 1149-55.
[PMID: 3183524]
Ketomäki A, Gylling H, Siimes MA, Vuorio A, Miettinen TA. Squalene and noncholesterol sterols in serum and lipoproteins of children with and without familial hypercholesterolemia. Pediatr Res 2003; 53(4): 648-53.
[] [PMID: 12612218]
Grundy SM, Ahrens EH Jr. Measurements of cholesterol turnover, synthesis, and absorption in man, carried out by isotope kinetic and sterol balance methods. J Lipid Res 1969; 10(1): 91-107.
[PMID: 5764121]
Smith FR, Dell RB, Noble RP, Goodman DS. Parameters of the three-pool model of the turnover of plasma cholesterol in normal and hyperlipidemic humans. J Clin Invest 1976; 57(1): 137-48.
[] [PMID: 1245596]
Bilheimer DW, Goldstein JL, Grundy SM, Brown MS. Reduction in cholesterol and low density lipoprotein synthesis after portacaval shunt surgery in a patient with homozygous familial hypercholesterolemia. J Clin Invest 1975; 56(6): 1420-30.
[] [PMID: 172531]
Carter GA, Connor WE, Bhattacharyya AK, Lin DS. The cholesterol turnover, synthesis, and absorption in two sisters with familial hypercholesterolemia (type IIa). J Lipid Res 1979; 20(1): 66-77.
[PMID: 220354]
Samuel P, Perl W, Holtzman CM, Rochman ND, Lieberman S. Long-term kinetics of serum and xanthoma cholesterol radioactivity in patients with hypercholesterolemia J Clin Invest 1972; 51(2): 266-278.22.
Férézou J, Virelizier H, Hagemann R, Chevallier F. Limits for using stable isotopes in studies of cholesterol metabolism in humans. Int J Appl Radiat Isot 1981; 32(7): 481-6.
[] [PMID: 7263096]
MacKay DS, Jones P. Limitations of lathosterol to plant sterol ratios and serum plant sterols as surrogate markers for cholesterol absorption during plant sterol supplementation. Nutr Metab Cardiovasc Dis 2012; 22(9)e21
[] [PMID: 22795297]
Miettinen TA, Gylling H, Hallikainen M, et al. Relation of non-cholesterol sterols to coronary risk factors and carotid intima-media thickness: the Cardiovascular Risk in Young Finns Study. Atherosclerosis 2010; 209(2): 592-7.
[] [PMID: 19963215]
Gylling H, Hallikainen M, Nissinen MJ, Simonen P, Miettinen TA. Very high plant stanol intake and serum plant stanols and non-cholesterol sterols. Eur J Nutr 2010; 49(2): 111-7.
[] [PMID: 19774436]
Qi Y, Liu J, Ma C, et al. Association between cholesterol synthesis/absorption markers and effects of cholesterol lowering by atorvastatin among patients with high risk of coronary heart disease. J Lipid Res 2013; 54(11): 3189-97.
[] [PMID: 23964121]
Ogishima T, Deguchi S, Okuda K. Purification and characterization of cholesterol 7 alpha-hydroxylase from rat liver microsomes. J Biol Chem 1987; 262(16): 7646-50.
[PMID: 3584134]
Okada K, Iwahashi N, Endo T, et al. Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease. Atherosclerosis 2012; 224(2): 454-6.
[] [PMID: 22892323]
Gojkovic T, Vladimirov S, Spasojevic-Kalimanovska V, et al. Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response? Clin Chem Lab Med 2017; 55(3): 447-57.
[] [PMID: 27718480]
Krawczyk M, Lütjohann D, Schirin-Sokhan R, et al. Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease. Hepatology 2012; 55(5): 1507-17.
[] [PMID: 22213168]
Koivusalo A, Pakarinen M, Gylling H, Nissinen MJ. Relation of cholesterol metabolism to pediatric gallstone disease: a retrospective controlled study. BMC Gastroenterol 2015; 15: 74.
[] [PMID: 26122832]
Noto D, Cefalù AB, Barraco G, et al. Plasma non-cholesterol sterols in primary hypobetalipoproteinemia. Atherosclerosis 2011; 216(2): 409-13.
[] [PMID: 21492858]
Jakulj L, Mohammed H, van Dijk TH, et al. Plasma plant sterols serve as poor markers of cholesterol absorption in man. J Lipid Res 2013; 54(4): 1144-50.
[] [PMID: 23178226]
Sudhop T, Sahin Y, Lindenthal B, et al. Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion. Gut 2002; 51(6): 860-3.
[] [PMID: 12427790]
Yu L, Gupta S, Xu F, et al. Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion. J Biol Chem 2005; 280(10): 8742-7.
[] [PMID: 15611112]
Yu L, Hammer RE, Li-Hawkins J, et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci USA 2002; 99(25): 16237-42.
[] [PMID: 12444248]
Yu L, Li-Hawkins J, Hammer RE, et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 2002; 110(5): 671-80.
[] [PMID: 12208868]
Salen G, Shefer S, Nguyen L, Ness GC, Tint GS, Shore V. Sitosterolemia. J Lipid Res 1992 Jul; 33(7): 945-55.
[PMID: 1431587]
Wilund KR, Yu L, Xu F, Hobbs HH, Cohen JC. High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr-/- mice. J Lipid Res 2004; 45(8): 1429-36.
[] [PMID: 15175362]
Miettinen TA, Klett EL, Gylling H, Isoniemi H, Patel SB. Liver transplantation in a patient with sitosterolemia and cirrhosis. Gastroenterology 2006; 130(2): 542-7.
[] [PMID: 16472606]
Nguyen DV, Drover VA, Knopfel M, Dhanasekaran P, Hauser H, Phillips MC. Influence of class B scavenger receptors on cholesterol flux across the brush border membrane and intestinal absorption. J Lipid Res 2009; 50(11): 2235-44.
[] [PMID: 19454765]
Lammert F, Wang DQ. New insights into the genetic regulation of intestinal cholesterol absorption. Gastroenterology 2005; 129(2): 718-34.
[] [PMID: 16083725]
Sudhop T, Gottwald BM, von Bergmann K. Serum plant sterols as a potential risk factor for coronary heart disease. Metabolism 2002; 51(12): 1519-21.
[] [PMID: 12489060]
Weingärtner O, Lütjohann D, Vanmierlo T, et al. Markers of enhanced cholesterol absorption are a strong predictor for cardiovascular diseases in patients without diabetes mellitus. Chem Phys Lipids 2011; 164(6): 451-6.
[] [PMID: 21501602]
Wilund KR, Yu L, Xu F, et al. No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol 2004; 24(12): 2326-32.
[] [PMID: 15514206]
Tilvis RS, Miettinen TA. Serum plant sterols and their relation to cholesterol absorption. Am J Clin Nutr 1986; 43(1): 92-7.
[] [PMID: 3942097]
Luister A, Schött HF, Husche C, et al. Increased plant sterol deposition in vascular tissue characterizes patients with severe aortic stenosis and concomitant coronary artery disease. Steroids 2015; 99(Pt B): 272-80.
Silbernagel G, Fauler G, Renner W, et al. The relationships of cholesterol metabolism and plasma plant sterols with the severity of coronary artery disease. J Lipid Res 2009; 50(2): 334-41.
[] [PMID: 18769018]
Andrade I, Santos L, Ramos F. Cholesterol absorption and synthesis markers in Portuguese hypercholesterolemic adults: A cross-sectional study. Eur J Intern Med 2016; 28: 85-90.
[] [PMID: 26577223]
Miettinen TA, Gylling H, Viikari J, Lehtimäki T, Raitakari OT. Synthesis and absorption of cholesterol in Finnish boys by serum non-cholesterol sterols: the cardiovascular risk in Young Finns Study. Atherosclerosis 2008; 200(1): 177-83.
[] [PMID: 18178213]
Silbernagel G, Fauler G, Hoffmann MM, et al. The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality. J Lipid Res 2010; 51(8): 2384-93.
[] [PMID: 20228406]
Nguyen LB, Shefer S, Salen G, et al. A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis. J Clin Invest 1990; 86(3): 923-31.
[] [PMID: 2394840]
Hansel B, Carrié A, Brun-Druc N, et al. Premature atherosclerosis is not systematic in phytosterolemic patients: severe hypercholesterolemia as a confounding factor in five subjects. Atherosclerosis 2014; 234(1): 162-8.
[] [PMID: 24657386]
Miettinen TA, Railo M, Lepäntalo M, Gylling H. Plant sterols in serum and in atherosclerotic plaques of patients undergoing carotid endarterectomy. J Am Coll Cardiol 2005; 45(11): 1794-801.
[] [PMID: 15936608]
Fassbender K, Lütjohann D, Dik MG, et al. Moderately elevated plant sterol levels are associated with reduced cardiovascular risk-the LASA study. Atherosclerosis 2008; 196(1): 283-8.
[] [PMID: 17137582]
Horenstein RB, Mitchell BD, Post WS, et al. The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the Old Order Amish. Arterioscler Thromb Vasc Biol 2013; 33(2): 413-9.
[] [PMID: 23241408]
Sanclemente T, Marques-Lopes I, Fajó-Pascual M, et al. Naturally-occurring phytosterols in the usual diet influence cholesterol metabolism in healthy subjects. Nutr Metab Cardiovasc Dis 2012; 22(10): 849-55.
[] [PMID: 21703833]
Hallikainen M, Simonen P, Gylling H. Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions. Lipids Health Dis 2014; 13: 72.
[] [PMID: 24766766]
Silbernagel G, Chapman MJ, Genser B, et al. High intestinal cholesterol absorption is associated with cardiovascular disease and risk alleles in ABCG8 and ABO: evidence from the LURIC and YFS cohorts and from a meta-analysis. J Am Coll Cardiol 2013; 62(4): 291-9.
[] [PMID: 23707316]
Lottenberg AM, Bombo RP, Nakandakare E, Quintão ER. After all plant sterol feeding protects against atherosclerosis. Atherosclerosis 2014; 233(2): 460.
[] [PMID: 24530779]
Bhattacharyya AK, Lin DS, Connor WE. Cholestanol metabolism in patients with cerebrotendinous xanthomatosis: absorption, turnover, and tissue deposition. J Lipid Res 2007; 48(1): 185-92.
[] [PMID: 17012751]
Duell PB, Salen G, Eichler FS, et al. Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis. J Clin Lipidol 2018; 12(5): 1169-78.
[] [PMID: 30017468]
Björkhem I, Skrede S, Buchmann MS, East C, Grundy S. Accumulation of 7 alpha-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one in patients with cerebrotendinous xanthomatosis: effect of treatment with chenodeoxycholic acid. Hepatology 1987; 7(2): 266-71.
[] [PMID: 3557306]
Miettinen TA, Tilvis RS, Kesäniemi YA. Serum cholestanol and plant sterol levels in relation to cholesterol metabolism in middle-aged men. Metabolism 1989; 38(2): 136-40.
[] [PMID: 2913464]
Lin X, Racette SB, Ma L, Wallendorf M, Spearie CA, Ostlund RE Jr. Plasma biomarker of dietary phytosterol intake. PLoS One 2015; 10(2)e0116912
[] [PMID: 25668184]
Lupattelli G, De Vuono S, Mannarino E. Patterns of cholesterol metabolism: pathophysiological and therapeutic implications for dyslipidemias and the metabolic syndrome. Nutr Metab Cardiovasc Dis 2011; 21(9): 620-7.
[] [PMID: 21855307]
Hallikainen M, Vidgren H, Agren JJ, Kiviniemi V, Miettinen TA, Gylling H. Postprandial behavior of plasma squalene and non-cholesterol sterols in men with varying cholesterol absorption. Clin Chim Acta 2006; 374(1-2): 63-8.
[] [PMID: 16814761]
Nikkilä K, Miettinen TA, Höckerstedt KV, Isoniemi H. Sterol parameters as markers of liver function in primary biliary cirrhosis before and after liver transplantation. Transpl Int 2005; 18(2): 221-5.
[] [PMID: 15691276]
Jakulj L, Vissers MN, Tanck MW, et al. ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis. J Lipid Res 2010; 51(10): 3016-23.
[] [PMID: 20581104]
Lütjohann D. Methodological aspects of plant sterol and stanol measurement. J AOAC Int 2015; 98(3): 674-6.
[] [PMID: 25942061]
Andrade I, Santos L, Ramos F. “Add-on” effect of phytosterols-enriched fermented milk on lipids and markers of cholesterol metabolism in statin-treated elderly patients. Steroids 2015 Jul; 99(Pt B): 293-8.
Nikkilä K, Höckerstedt K, Miettinen TA. High serum cholestanol and low campesterol/sitosterol ratio indicate severe liver damage and liver transplantation in primary biliary cirrhosis. Transplant Proc 1992a; 24(1): 383-6.
[PMID: 1539326]
Nikkilä K, Höckerstedt K, Miettinen TA. Serum and hepatic cholestanol, squalene and noncholesterol sterols in man: a study on liver transplantation. Hepatology 1992b; 15(5): 863-70.
[] [PMID: 1568728]
Gylling H, Vuoristo M, Färkkilä M, Miettinen TA. The metabolism of cholestanol in primary biliary cirrhosis. J Hepatol 1996; 24(4): 444-51.
[] [PMID: 8738731]
Vanhanen HT, Kajander J, Lehtovirta H, Miettinen TA. Serum levels, absorption efficiency, faecal elimination and synthesis of cholesterol during increasing doses of dietary sitostanol esters in hypercholesterolaemic subjects. Clin Sci (Lond) 1994; 87(1): 61-7.
[] [PMID: 8062521]
Miettinen TA, Hallikainen M, Raitakari OT, Viikari J, Gylling H. Twenty-one year tracking of serum non-cholesterol sterols. The cardiovascular risk in young Finns study. Nutr Metab Cardiovasc Dis 2009; 19(8): 525-31.
[] [PMID: 19185477]
Vanhanen HT, Miettinen TA. Cholesterol absorption and synthesis during pravastatin, gemfibrozil and their combination. Atherosclerosis 1995; 115(2): 135-46.
[] [PMID: 7661873]
Kishimoto M, Sugiyama T, Osame K, Takarabe D, Okamoto M, Noda M. Efficacy of ezetimibe as monotherapy or combination therapy in hypercholesterolemic patients with and without diabetes. J Med Invest 2011; 58(1-2): 86-94.
[] [PMID: 21372492]
Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res 1995; 36(8): 1807-12.
[PMID: 7595101]
Gylling H, Rajaratnam RA, Vartiainen E, Puska P, Miettinen TA. Changes in serum level and metabolism of cholesterol with plant stanol esters in postmenopausal women with and without coronary artery disease. Menopause 2006; 13(2): 286-93.
[] [PMID: 16645542]
Miettinen TE, Vuoristo M. The sedimentable sterols in gallstone patients before and during ursodeoxycholic acid and simvastatin treatments. Scand J Gastroenterol 1998; 33(12): 1297-302.
[] [PMID: 9930394]
Koivisto PV, Miettinen TA. Plasma and biliary cholestanol related to steroid metabolism in familial hypercholesterolemia patients with and without ileal exclusion. Clin Chim Acta 1988; 174(2): 197-205.
[] [PMID: 3133140]
Miettinen TA, Kesäniemi YA, Järvinen H, Hästbacka J. Cholesterol precursor sterols, plant sterols, and cholestanol in human bile and gallstones. Gastroenterology 1986; 90(4): 858-64.
[] [PMID: 3081398]
Lindenthal B, Sudhop T, Schiedermaier P, Agnan M, Sauerbruch T, von Bergmann K. Serum plant sterols and biliary cholesterol secretion in humans: studies with ursodeoxycholic acid. J Lipid Res 2002; 43(7): 1072-7.
[] [PMID: 12091491]
Stellaard F, von Bergmann K, Sudhop T, Lütjohann D. The value of surrogate markers to monitor cholesterol absorption, synthesis and bioconversion to bile acids under lipid lowering therapies. J Steroid Biochem Mol Biol 2017; 169: 111-22.
[] [PMID: 27060336]
Gylling H, Hallikainen M, Rajaratnam RA, et al. The metabolism of plant sterols is disturbed in postmenopausal women with coronary artery disease. Metabolism 2009; 58(3): 401-7.
[] [PMID: 19217458]
Schonewille M, de Boer JF, Mele L, et al. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice. J Lipid Res 2016; 57(8): 1455-64.
[] [PMID: 27313057]
Lupattelli G, Pirro M, Siepi D, et al. Non-cholesterol sterols in different forms of primary hyperlipemias. Nutr Metab Cardiovasc Dis 2012; 22(3): 231-6.
[] [PMID: 20708389]
Baila-Rueda L, Pérez-Ruiz MR, Jarauta E, et al. Cosegregation of serum cholesterol with cholesterol intestinal absorption markers in families with primary hypercholesterolemia without mutations in LDLR, APOB, PCSK9 and APOE genes. Atherosclerosis 2016; 246: 202-7.
[] [PMID: 26802983]
van Himbergen TM, Otokozawa S, Matthan NR, et al. Familial combined hyperlipidemia is associated with alterations in the cholesterol synthesis pathway. Arterioscler Thromb Vasc Biol 2010; 30(1): 113-20.
[] [PMID: 19834104]
Baila-Rueda L, Cenarro A, Lamiquiz-Moneo I, et al. Cholesterol oversynthesis markers define familial combined hyperlipidemia versus other genetic hypercholesterolemias independently of body weight. J Nutr Biochem 2018; 53: 48-57.
[] [PMID: 29190549]
Lamiquiz-Moneo I, Baila-Rueda L, Bea AM, et al. ABCG5/G8 gene is associated with hypercholesterolemias without mutation in candidate genes and noncholesterol sterols. J Clin Lipidol 2017; 11(6): 1432-40.e4.
[] [PMID: 29066094]
Martín B, Solanas-Barca M, García-Otín AL, et al. An NPC1L1 gene promoter variant is associated with autosomal dominant hypercholesterolemia. Nutr Metab Cardiovasc Dis 2010; 20(4): 236-42.
[] [PMID: 19747803]
García-Otín AL, Cofán M, Junyent M, et al. Increased intestinal cholesterol absorption in autosomal dominant hypercholesterolemia and no mutations in the low-density lipoprotein receptor or apolipoprotein B genes. J Clin Endocrinol Metab 2007; 92(9): 3667-73.
[] [PMID: 17566095]
Gylling H, Aalto-Setälä K, Kontula K, Miettinen TA. Serum low density lipoprotein cholesterol level and cholesterol absorption efficiency are influenced by apolipoprotein B and E polymorphism and by the FH-Helsinki mutation of the low density lipoprotein receptor gene in familial hypercholesterolemia. Arterioscler Thromb 1991; 11(5): 1368-75.
[] [PMID: 1911722]
Gylling H, Korhonen M, Mutanen A, Nissinen MJ, Pakarinen M, Simonen P. Serum non-cholesterol sterols and cholesterol metabolism in childhood and adolescence. Atherosclerosis 2018; 278: 91-6.
Vuorio AF, Miettinen TA, Turtola H, Oksanen H, Gylling H. Cholesterol metabolism in normal and heterozygous familial hypercholesterolemic newborns. J Lab Clin Med 2002; 140(1): 35-42.
[] [PMID: 12080326]
Noto D, Cefalù AB, Barraco G, et al. Plasma non-cholesterol sterols: a useful diagnostic tool in pediatric hypercholesterolemia. Pediatr Res 2010; 67(2): 200-4.
[] [PMID: 20091938]
Ketomaki A, Gylling H, Miettinen TA. Effects of plant stanol and sterol esters on serum phytosterols in a family with familial hypercholesterolemia including a homozygous subject. J Lab Clin Med 2004; 143(4): 255-62.
[] [PMID: 15085084]
Zavoral JH, Laine DC, Bale LK, et al. Cholesterol excretion studies in familial hypercholesterolemic children and their normolipidemic siblings. Am J Clin Nutr 1982; 35(6): 1360-7.
[] [PMID: 7081118]
Strandberg TE, Gylling H, Tilvis RS, Miettinen TA. Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year mortality among middle-aged men. Atherosclerosis 2010; 210(1): 282-7.
[] [PMID: 19962145]
Nunes VS, Bensenor IM, Lotufo PA, Passarelli M, Nakandakare ER, Quintão ECR. The coronary artery calcium score is linked to plasma cholesterol synthesis and absorption markers. The Brazilian Study of Adult Health 2020; 40(7)BSR20201094
Baila-Rueda L, Mateo-Gallego R, Jarauta E, et al. Bile acid synthesis precursors in familial combined hyperlipidemia: the oxysterols 24S-hydroxycholesterol and 27-hydroxycholesterol. Biochem Biophys Res Commun 2014; 446(3): 731-5.
[] [PMID: 24406166]
Gylling H, Hallikainen M, Pihlajamäki J, et al. Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity. J Lipid Res 2004; 45(9): 1660-5.
[] [PMID: 15175352]
McNamara DJ, Ahrens EH Jr, Kolb R, et al. Treatment of familial hypercholesterolemia by portacaval anastomosis: effect on cholesterol metabolism and pool sizes. Proc Natl Acad Sci USA 1983; 80(2): 564-8.
[] [PMID: 6572906]
Paramsothy P, Knopp RH, Kahn SE, et al. Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity. Am J Clin Nutr 2011; 94(5): 1182-8.
[] [PMID: 21940599]
Rajaratnam RA, Gylling H, Miettinen TA. Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women. J Am Coll Cardiol 2000; 35(5): 1185-91.
[] [PMID: 10758959]
Gylling H, Hallikainen M, Pihlajamäki J, et al. Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study. J Lipid Res 2010; 51(8): 2422-7.
[] [PMID: 20436182]
Miettinen TA, Gylling H. Cholesterol absorption efficiency and sterol metabolism in obesity. Atherosclerosis 2000; 153(1): 241-8.
[] [PMID: 11058720]
Pihlajamäki J, Gylling H, Miettinen TA, Laakso M. Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. J Lipid Res 2004; 45(3): 507-12.
[] [PMID: 14657199]
Cofán M, Escurriol V, García-Otín AL, et al. Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study. Nutr Metab Cardiovasc Dis 2011; 21(9): 651-7.
[] [PMID: 20554170]
Ooi EM, Ng TW, Chan DC, Watts GF. Plasma markers of cholesterol homeostasis in metabolic syndrome subjects with or without type-2 diabetes. Diabetes Res Clin Pract 2009; 85(3): 310-6.
[] [PMID: 19573945]
Sutherland WH, Scott RS, Lintott CJ, Robertson MC, Stapely SA, Cox C. Plasma non-cholesterol sterols in patients with non-insulin dependent diabetes mellitus. Horm Metab Res 1992; 24(4): 172-5.
[] [PMID: 1601392]
Simonen P, Gylling H, Miettinen TA. Acute effects of weight reduction on cholesterol metabolism in obese type 2 diabetes. Clin Chim Acta 2002; 316(1-2): 55-61.
[] [PMID: 11750274]
Miettinen TA, Gylling H, Tuominen J, Simonen P, Koivisto V. Low synthesis and high absorption of cholesterol characterize type 1 diabetes. Diabetes Care 2004; 27(1): 53-8.
[] [PMID: 14693966]
Shay CM, Evans RW, Orchard TJ. Do plant sterol concentrations correlate with coronary artery disease in type 1 diabetes? A report from the Pittsburgh epidemiology of diabetes complications study. J Diabetes 2009; 1(2): 112-7.
[] [PMID: 20827426]
Nunes VS, Cazita PM, Catanozi S, Nakandakare ER, Quintão ECR. Cholesterol metabolism in mice models of genetic hypercholesterolemia. J Physiol Biochem 2020; 76(3): 437-43.
[] [PMID: 32557226]
Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol 2009; 29(4): 431-8.
[] [PMID: 19299327]
Ishibashi S, Herz J, Maeda N, Goldstein JL, Brown MS. The two-receptor model of lipoprotein clearance: tests of the hypothesis in “knockout” mice lacking the low density lipoprotein receptor, apolipoprotein E, or both proteins. Proc Natl Acad Sci USA 1994; 91(10): 4431-5.
[] [PMID: 8183926]

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