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ORIGINAL RESEARCH COMMUNICATION |
1 From the Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, University of Reading, Reading, United Kingdom (WLH, KV, A-MM, and CMW); the Department of Human Nutrition, Centre for Advanced Food Studies, The Royal Veterinary and Agricultural University, Frederiksberg, Denmark (JH and SB); the German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany (CK and H-JFZ); the National Institute for Food and Nutrition Research, Rome, Italy (MF and FB); Unilever Corporate Research, Sharnbrook, United Kingdom (DT and JP); the Departments of Biosciences and Medical Nutrition, Karolinska Institute, Huddinge, Sweden (MN, KD-W, and J-AG); and the School of Medicine, Health Policy & Practice, University of East Anglia, Norwich, United Kingdom (AC)
Background: The hypocholesterolemic effects of soy foods are well established, and it has been suggested that isoflavones are responsible for this effect. However, beneficial effects of isolated isoflavones on lipid biomarkers of cardiovascular disease risk have not yet been shown.
Objective: The objective was to investigate the effects of isolated soy isoflavones on metabolic biomarkers of cardiovascular disease risk, including plasma total, HDL, and LDL cholesterol; triacylglycerols; lipoprotein(a); the percentage of small dense LDL; glucose; nonesterified fatty acids; insulin; and the homeostasis model assessment of insulin resistance. Differences with respect to single nucleotide polymorphisms in selected genes [ie, estrogen receptor 
(XbaI and PvuII), estrogen receptor ß (AluI), and estrogen receptor ß(cx) (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), cholesteryl ester transfer protein (TaqIB), and leptin receptor (Gln223Arg)] and with respect to equol production were investigated.
Design: Healthy postmenopausal women (n = 117) participated in a randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a wash-out period of 8 wk before the crossover.
Results: Isoflavones did not have a significant beneficial effect on plasma concentrations of lipids, glucose, or insulin. A significant difference between the responses of HDL cholesterol to isoflavones and to placebo was found with estrogen receptor ß(cx) Tsp509I genotype AA, but not GG or GA.
Conclusions: Isoflavone supplementation, when provided in the form and dose used in this study, had no effect on lipid or other metabolic biomarkers of cardiovascular disease risk in postmenopausal women but may increase HDL cholesterol in an estrogen receptor ß gene–polymorphic subgroup.
Key Words: Isoflavones • soy • cardiovascular disease • postmenopausal women • plasma lipids • cholesterol • triacylglycerols • glucose • insulin • estrogen receptor • gene-nutrient interaction
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