The metabolic syndrome (MetS) is comprised of a constellation of cardiovascular risk factors rooted in the current epidemic of obesity. Two of the defining features of MetS are high triglycerides and low HDL, i.e. the dyslipidemia of MetS. Standard hygienic recommendations for this dyslipidemia are weight loss and exercise, but at weight stability, there is no consensus on the dietary fat and carbohydrate proportions best suited for the dyslipidemia or the associated impaired vascular reactivity of MetS. Diets higher in fat, lower in carbohydrate may be more beneficial in MetS. Weight-loss studies show that higher fat, lower carbohydrate intakes are associated with lower triglyceride levels in obese persons, but lipoprotein, inflammatory and vascular responses to dietary perturbation in weight stability (the usual physiological state) have not been studied prospectively. Standard low fat, high carbohydrate diets in dyslipidemic persons yield 1/3rd of the LDL lowering of persons with simple hypercholesterolemia. Such persons are also less sensitive to higher saturated fat feeding. Consistent with these findings are lower rates of coronary disease in persons ingesting higher fat diets in observational studies. These observations plus physiological reasoning suggest the following hypothesis: Higher fat intake is more beneficial than conventional fat restricted diet in MetS for;1) managing dyslipidemia, 2) reducing inflammatory stress and 3) correcting endothelium-mediated vascular reactivity, an immediate index of atherosclerotic stress. The study will compare the lipoprotein and vascular effects of two diets distinct in fat and carbohydrate content in a randomized, 4-week, crossover, feeding study design, using food prepared in the metabolic kitchen of the University of Washington GCRC. Diets will contain 40en% fat. 45en% carbohydrate or 20en% fat. 65en% carbohydrate with equivalent protein (15en%) and saturated fat (8en%). Weight will remain stable. Eligibility criteria are triglyceride >150mg/dl and any two other criteria of MetS. Seventy-two men and women will be randomized to yield 60 finished subjects at a 20% drop out rate. Weight and other vital signs will be measured twice weekly when food is picked-up from the GCRC. Lipoprotein lipids will be measured at 0, 3 and 4 weeks. Apoproteins B and A-l, LDL buoyancy, glucose, insulin, adiponectin, inflammatory cytokines and flow-mediated brachial artery reactivity will be measured at 0 and 4 weeks. A 4-month extension will continue the second diet assignment under dietician counseling with repeat testing. Expected results: 40en% fat diet in MetS subjects will yield improvements in non-HDL-C, other lipoprotein and glycemic variables, inflammation and brachial reactivity compared to 20en% fat. This study will be the first to demonstrate dietary benefit for dyslipidemia, inflammation and vascular stress in MetS at stable weight.
| Knopp, Robert H; Paramsothy, Pathmaja; Atkinson, Benjamin et al. (2008) Comprehensive lipid management versus aggressive low-density lipoprotein lowering to reduce cardiovascular risk. Am J Cardiol 101:48B-57B |
| Knopp, Robert H; Fish, Brian; Dowdy, Alice et al. (2006) A moderate-fat diet for combined hyperlipidemia and metabolic syndrome. Curr Atheroscler Rep 8:492-500 |
