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Biochemical, Molecular, and Genetic Mechanisms

Serum Lipid and Antioxidant Responses in Hypercholesterolemic Men and Women Receiving Plant Sterol Esters Vary by Apolipoprotein E Genotype^1,2

³ Departamento de Nutrición y Bromatología I (Nutrición), Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain ⁴ Provident Clinical Research (formerly with the Chicago Center for Clinical Research), Chicago, IL ⁵ Lipid Metabolism Laboratory ⁶ Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA

Plant sterol esters reduce serum total cholesterol (TC) and LDL cholesterol (LDL-C), but with striking interindividual variability. In this randomized, double-blind, controlled study, serum lipid, plant sterol, fat-soluble vitamin, and carotenoid responses to plant sterols were studied according to the apolipoprotein E (ApoE) genotype in 217 hypercholesterolemic adults. Subjects received a reduced saturated fat and cholesterol diet for 4 wk, followed by a 5-wk intervention during which they consumed a control spread (n = 87) or a spread with plant sterol esters (1.1 g/d or 2.2 g/d plant sterols; n = 120). Twenty-six subjects carried the E2 allele (E2E2 and E2E3), 51 had the E4 allele (E3E4+E4E4), and 130 were E3 homozygotes. Ten E2E4 carriers were not studied. At baseline, the serum triacylglycerol (TAG) concentration was lower in E4 subjects than in E3 subjects, -tocopherol was lower in E4 subjects than in E2 individuals, and LDL-C was lower in E2 carriers than in E3 and E4 carriers (P < 0.05 for all). During sterol consumption, TC, LDL-C, and ApoB concentrations and the TC:LDL-C and LDL-C:HDL-C ratios decreased in only E2 and E3 subjects and TAG decreased in only E2 subjects (all P < 0.05 vs. control). Significant reductions in serum carotenoids (P < 0.05 vs. control) were demonstrated for some alleles: β-carotene and lycopene in E2 and E4; -carotene in E3; cryptoxanthin in E3 and E4; zeaxanthin in E4; lycopene in E2 and E4; and lutein in E2 carriers. Thus, responses to plant sterols vary by ApoE genotype and may be of little value in ApoE4 carriers, who had reductions in serum carotenoid concentrations but not in TC, LDL-C, or ApoB.

^* To whom correspondence should be addressed. E-mail: frasan{at}farm.ucm.es.

Manuscript received 1 April 2008. Initial review completed 4 May 2008. Revision accepted 15 October 2008.