Flax: Safety & Efficacy in Reducing Cardiovascular Risk

描述（由申请方提供）：高胆固醇血症是动脉粥样硬化性心血管疾病（ASCVD）的重要既定风险因素。 国家胆固醇教育计划（NCEP）最近估计，1亿美国人有资格治疗他们的高胆固醇血症。 在这些美国人中，有6500万人可以单独通过饮食和运动来管理，这被最新的NCEP指南称为治疗性生活方式改变（TLC）。 NCEP已经认识到饮食和补充替代医学（CAM）疗法在血脂异常管理中的重要性，将可溶性纤维和植物性甾烷醇酯作为TLC的一部分。 亚麻籽是一种独特的食物，因为它含有大量的可溶性纤维以及最丰富的α-亚麻酸（ALA）和植物雌激素木脂素来源，这些都与预防ASCVD有关。 由于亚麻籽含有这些成分，它可能在未来的TLC中发挥重要作用，但目前缺乏数据。 此外，由于木脂素可以结合到雌激素受体，并引起激素反应，慢性亚麻籽消费可能有不良的激素作用。 因此，在这个项目中，我们建议系统地评估在短期内摄入亚麻籽粉对高胆固醇血症男性和女性的安全性和有效性。 这将在一项双盲、随机、安慰剂对照临床试验中完成。 由于对亚麻籽对男性的代谢影响知之甚少，随机化将按性别分层。 亚麻籽粉的测试剂量为40克，以烘焙产品形式给药，并与匹配的麦麸对照品进行比较。 本研究的主要终点是评估亚麻籽消费对脂质代谢和氧化应激的影响。 脂质代谢方面的主要应答变量包括低密度脂蛋白（LDL-C）胆固醇和餐后甘油三酯。 对于氧化应激的评价，主要的反应变量将是尿异前列腺素分泌，体内氧化损伤的最敏感的标志物。 关注的次要变量将包括胆固醇代谢、血管炎症、内分泌功能、安全性和可接受性的标志物。 这项研究的结果将为研究亚麻籽补充剂在调节心血管风险方面的临床和生化作用奠定基础。 具体而言，该项目产生的数据将用作向NCCAM和NHLBI提交R 01的初步数据，以研究亚麻籽的各种成分对ASCVD风险患者的脂质代谢和临床终点的长期影响和作用机制。

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.