Relationship between phytosterol levels and components of the metabolic syndrome in the PROCAM study

Abstract

Background

Components of the metabolic syndrome such as hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol and obesity have been shown to be associated with increased cholesterol synthesis and reduced cholesterol absorption. In the present study, we measured the lathosterol/cholesterol ratio as an index of cholesterol synthesis and the ratios of cholestanol, campesterol and sitosterol to cholesterol as indices of cholesterol absorption, as well as components of the metabolic syndrome, in 324 men and 168 women from the PROCAM study, an epidemiological study in which raised sitosterol was previously associated with increased coronary risk. Our aim was to determine if the indices of cholesterol synthesis and absorption show a graded relationship with severity of metabolic syndrome.

Results

No differences were seen between men and women with regard to the relationship of either the lathosterol/cholesterol or the sitosterol/cholesterol ratios and severity of metabolic syndrome. On multiple regression analysis in men and women together, body mass index showed a positive relationship with the lathosterol/cholesterol ratio (r=0.257, P<0.001) and a negative relationship with the sitosterol/cholesterol ratio (r=-0.221, P<0.001). HDL-cholesterol showed a negative relationship with the lathosterol/cholesterol ratio (r=-0.166, P=0.001). Triglycerides showed a negative relationship with the sitosterol/cholesterol ratio (r=0.141, P=0.005). Overall, these relationships were graded across quintiles of HDL cholesterol, body mass index and triglyceride and across an index of metabolic syndrome severity (number of components present). Only the cholestanol/cholesterol ratio showed a graded relationship with estimated overall coronary risk.

Conclusions

The metabolic syndrome is associated with increased cholesterol synthesis and reduced cholesterol absorption in a relationship that is graded across severity of the individual components of the syndrome and across an index of the severity of the metabolic syndrome as a whole.

Keywords

coronary risk metabolic syndrome phytosterol sitosterol sterol metabolism

Get full access to this article

View all access options for this article.

References

Salen

Ahrens

Jr Grundy

SM.

Metabolism of beta-sitosterol in man.

J Clin Invest 1970; 49:952–967.

Heinemann

Axtmann

von Bergmann

Comparison of intestinal absorption of cholesterol with different plant sterols in man.

Eur J Clin Invest 1993; 23:827–831.

3 Berge

von Bergmann

Lutjohann

Guerra

Grundy

Hobbs

, et al. Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J Lipid Res 2002; 43:486–494.

Boomsma

Princen

Frants

Gevers Leuven

Kempen

HJ.

Genetic analysis of indicators of cholesterol synthesis and absorption: lathosterol and phytosterols in Dutch twins and their parents.

Twin Res 2003; 6:307–314.

5 Berge

Tian

Graf

Grishin

Schultz

, et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000; 290:1771–1775.

Bhattacharyya

Connor

Lin

McMurry

Shulman

RS.

Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis.

Arterioscler Thromb 1991; 11:1287–1294.

Bhattacharyya

Connor

WE.

Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters.

J Clin Invest 1974; 53:1033–1043.

Rajaratnam

Gylling

Miettinen

TA.

Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women.

J Am Coll Cardiol 2000; 35:1185–1191.

Glueck

Speirs

Tracy

Streicher

Illig

Vandegrift

Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives.

Metabolism 1991; 40:842–848.

10.

Sudhop

Gottwald

von Bergmann

Serum plant sterols as a potential risk factor for coronary heart disease.

Metabolism 2002; 51:1519–1521.

11.

Assmann

Cullen

Erbey

Ramey

Kannenberg

Schulte

Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: Results of a nested case–control analysis of the Prospective Cardiovascular Munster (PROCAM) study.

Nutr Metab Cardiovasc Dis 2006; 16:13–21.

12.

Gylling

Miettinen

TA.

Cholesterol absorption: influence of body weight and the role of plant sterols.

Curr Atheroscler Rep 2005; 7:466–471.

13.

Simonen

Gylling

Miettinen

TA.

Body weight modulates cholesterol metabolism in non-insulin dependent type 2 diabetics.

Obes Res 2002; 10:328–335.

14.

Assmann

Schulte

The Prospective Cardiovascular Munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease.

Am Heart J 1988; 116:1713–1724.

15.

Kempen

de Knijff

Boomsma

van der Voort

Gevers Leuven

Havekes

Plasma levels of lathosterol and phytosterols in relation to age, sex, anthropometric parameters, plasma lipids, and apolipoprotein E phenotype, in 160 Dutch families.

Metabolism 1991; 40:604–611.

16.

Miettinen

Tilvis

Kesaniemi

YA.

Serum cholestanol and plant sterol levels in relation to cholesterol metabolism in middle-aged men.

Metabolism 1989; 38:136–140.

17.

Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).

JAMA 2001; 285:2486–2497.

18.

Klansek

Yancey

Clair

St Fischer

Johnson

Glick

JM.

Cholesterol quantitation by GLC: artifactual formation of short-chain steryl esters.

J Lipid Res 1995; 36:2261–2266.

19.

Kannenberg

Development of a new procedure for analysing bile acids bymeans of coupled gas chromatography/mass spectrometry. Identification and quantification of abnormal metabolites in bile and serum in disorders of bile salt metabolism [PhD Thesis]. Univeristy of Muenster; 2001.

20.

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.

Circulation 2002; 106:3143–3421.

21.

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus.

Diabetes Care 1998; 21:S5–S19.

22.

Assmann

Cullen

Schulte

Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study.

Circulation 2002; 105:310–315.

23.

Miettinen

TA.

Cholesterol production in obesity.

Circulation 1971; 44:842–850.

24.

Nestel

Schreibman

Ahrens

Jr.

Cholesterol metabolism in human obesity.

J Clin Invest 1973; 52:2389–2397.

25.

Miettinen

Gylling

Cholesterol absorption efficiency and sterol metabolism in obesity.

Atherosclerosis 2000; 153:241–248.

26.

Simonen

Gylling

Miettinen

TA.

Diabetes contributes to cholesterol metabolism regardless of obesity.

Diabetes Care 2002; 25:1511–1515.

27.

Miettinen

Gylling

Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup.

Atherosclerosis 2003; 168:343–349.

28.

Chan

Watts

Barrett

O'Neill

Redgrave

Thompson

GR.

Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome.

Clin Sci (Lond) 2003; 104:383–388.

29.

Miettinen

Tilvis

Kesaniemi

YA.

Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population.

Am J Epidemiol 1990; 131:20–31.

30.

Miettinen

Gylling

Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup.

Atherosclerosis 2003; 168:343–349.

31.

31 Gylling

Hallikainen

Pihlajamaki

Agren

Laakso

Rajaratnam

, et al. Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity. J Lipid Res 2004; 45:1660–1665.

32.

Nestel

Goldrick

Obesity: changes in lipid metabolism and the role of insulin.

Clin Endocrinol Metab 1976; 5:313–335.

33.

Miettinen

Gylling

Strandberg

Sarna

Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators.

BMJ 1998; 316:1127–1130.

34.

Miettinen

Strandberg

Gylling

Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol.

Arterioscler Thromb Vasc Biol 2000; 20:1340–1346.

35.

Miettinen

Gylling

Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup.

Atherosclerosis 2003; 168:343–349.

36.

Gylling

Miettinen

TA.

Cholesterol absorption and lipoprotein metabolism in type II diabetes mellitus with and without coronary artery disease.

Atherosclerosis 1996; 126:325–332