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Title: Serum lipid and antioxidant responses in hypercholesterolemic men and women receiving plant sterol esters vary by apolipoprotein E genotype

Author
item SANCHEZ-MUNIZ, FRANCISCO - University Of Madrid
item MAKI, KEVIN - Provident Clinical Research
item SCHAEFER, ERNST - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/15/2008
Publication Date: 12/3/2008
Citation: Sanchez-Muniz, F., Schaefer, E.J., Ordovas, J. 2008. Serum lipid and antioxidant responses in hypercholesterolemic men and women receiving plant sterol esters vary by apolipoprotein E genotype. Journal of Nutrition. 139:13-19.

Interpretive Summary: Blood cholesterol levels are major risk factors for cardiovascular disease, the major cause of morbidity and mortality in the USA. Dietary and pharmacological interventions have been used to reduce blood cholesterol levels in order to achieve better prevention and therapy of these devastating diseases. However, the individual responses to any type of therapy are very variable and a wide spectrum of alternatives is needed to achieve benefits for the entire population at risk. Plant sterols are being recommended in conjunction with reductions of dietary saturated fat as nutritional tools to reduce blood cholesterol levels. However, some people respond to plant sterols better than others, and this information can be used to achieve a more personalized and efficacious dietary recommendations. In order to tease out responders and non responders, we tested if common genetic variants in the apolipoprotein E (APOE) gene, which is involved in lipid metabolism, may explain some of the variability in response. For this purpose, we studied responses to plant sterols according to the APOE genotype in 217 hypercholesterolemic adults. Subjects received a reduced saturated fat and cholesterol diet for 4 weeks, followed by a 5-week intervention during which they consumed a control spread or a spread with plant sterol esters (1.1 g/d or 2.2 g/d plant sterols). Our results show that 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 the levels of total blood cholesterol. Therefore, this data supports the notion of personalized nutrition and suggest that those individuals carrying the APOE4 form of the APOE gene may not benefit from consuming plant sterols and alternative recommendations should investigated.

Technical Abstract: Plant sterol esters reduce serum total cholesterol (TC) and LDL cholesterol (LDL-C), but with striking inter-individual 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 weeks, followed by a 5-week intervention during which they consumed a control spread (n1**487) or a spread with plant sterol esters (1.1 g/d or 2.2 g/d plant sterols; n1**4120). Twenty six subjects carried the E2 allele (E2E2 and E2E3), 51 had the E4 allele (E3E41E4E4), 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, a-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 LDLC: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: b-carotene and lycopene in E2 and E4; a-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.