Flax: Safety & Efficacy in Reducing Cardiovascular Risk

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DESCRIPTION (provided by applicant): Hypercholesterolemia is an important established risk factor for atherosclerotic cardiovascular disease (ASCVD). The National Cholesterol Education Program (NCEP) has recently estimated that 100 million Americans qualify for treatment of their hypercholesterolemia. Of these Americans, 65 million could be managed with diet and exercise alone, referred to as Therapeutic Lifestyle Changes (TLC) by the most recent NCEP guidelines. The NCEP has already recognized the importance of diet and Complementary Alternative Medicine (CAM) therapies in the management of dyslipidemia by incorporating soluble fiber and plant-based stanol esters as part of TLC. Flaxseed is a unique food as it contains significant amounts of soluble fiber as well as the richest source of both alpha-linolenic acid (ALA) and phytoestrogenic lignans, which have all been implicated in the prevention of ASCVD. Because flaxseed contains these constituents, it may play an important role in TLC in the future, but data is currently lacking. In addition, because lignans can bind to the estrogen receptor and elicit a hormonal response, chronic flaxseed consumption may have undesirable hormonal effects. Thus in this project, we propose to systematically evaluate the safety and efficacy of ground flaxseed ingestion in both men and women with hypercholesterolemia over the short term. This will be done in a single double-blind, randomized, placebo controlled clinical trial. Because little is known about the metabolic effects of flaxseed in men, randomization will be stratified by gender. The test dose of flaxseed meal will be 40 grams administered in baked products and compared to a matching wheat bran control. The primary endpoints of this study are to evaluate the effects of flaxseed consumption on lipid metabolism and oxidative stress. The primary response variables in terms of lipid metabolism will include low density lipoprotein (LDL-C) cholesterol and post-prandial triglycerides. For the evaluation of oxidant stress, the primary response variable will be urinary isoprostane secretion, the most sensitive marker of in vivo oxidative damage. Secondary variables of interest will include markers of cholesterol metabolism, vascular inflammation, endocrine function, safety and acceptibility. The results from this study will lay the foundation for several lines of research into the clinical and biochemical effects of flaxseed supplementation in modulating cardiovascular risk. Specifically, the data generated from this project will be used as preliminary data to pursue R01 submissions to NCCAM and NHLBI to investigate the long-term effects and mechanisms of action of the various components of flaxseed on lipid metabolism and clinical endpoints in patients at risk for ASCVD.