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Functional foods with supplementation of plant sterols are already used by millions of people. However, at the same time it is current scientific thinking that elevation of plant sterols in the circulation causes coronary heart disease. Therefore, this study aimed to define the risk for coronary heart disease associated with moderately high plant sterol plasma levels in a cohort of elderly. In this study, we evaluated the association between plant sterols and coronary heart disease in a cohort of 1242 subjects older than 65 years, participating at the Longitudinal Aging Study Amsterdam (LASA). Concentrations of sitosterol, campesterol, brassicasterol and stigmasterol were assessed using highly sensitive and specific gas chromatography-mass spectrometry-selected ion-monitoring. Plant sterol concentrations (and their ratios to cholesterol) were slightly, however, significantly lower in patients with coronary heart disease. Moreover, high plasma concentrations of a marker plant sterol, sitosterol, were associated with a markedly reduced risk for coronary heart disease (OR 0.78, CI 0.62-0.98, p<0.05). In contrast neither plant stanols (sitostanol or campestanol) nor the cholesterol synthesis markers (lathosterol, lanosterol and desmosterol) nor their ratios to cholesterol were significantly different in the study groups. These data suggest that plant sterols could have neutral or even protective effects on development of coronary heart disease, which have to be confirmed in interventional trials.

Sterol regulatory element binding proteins-1 and -2 (SREBPs) are transcription factors controlling lipid homeostasis in human cells. The G-allele carriers of the SREBF-1 gene C-G polymorphism in exon 18c and coding for glycine at the protein level (G952G) have shown to associate more frequently with obesity and type 2 diabetes than the C-allele carriers. However, the C-allele has suggested to be linked to dyslipidemia. Thus, our aim was to study effect of the SREBF-1 gene polymorphism (G952G) on sterol metabolism in man. Ninety-five subjects with moderate hypercholesterolemia participated in this study and 14 homozygous CC carriers of the SREBF-1 (G952G) gene were found. Plasma lathosterol concentration and lathosterol-to-cholesterol ratio, markers of endogenous cholesterol synthesis, were significantly higher in CC homozygous subject compared to others. Similarly muscle cholesterol (p=0.045) and lathosterol (p=0.054) concentrations were elevated in the CC homozygotes supporting the view that endogenous cholesterol synthesis rate is SREBF-1 genotype-dependent.