ALA & EPA/DHA (w-3) Effects On Inflammatory Markers in Insulin Resistant Adults

背景：一种特殊类型的膳食多不饱和脂肪- omega-3脂肪酸(w-3 FAs) -已被发现对心血管疾病死亡具有保护作用。膳食中w-3脂肪酸一般有两种来源：海洋来源提供EPA和DHA，植物食物来源提供ALA。它们也被广泛用作营养补充剂。究竟哪一种形式在预防疾病方面更有效，仍然存在争议。争议的部分原因是对不同来源和（或）不同研究对象的最佳剂量缺乏共识。对于那些甘油三酯和炎症标志物水平升高的胰岛素抵抗（代谢综合征）患者，潜在的益处可能会增加。长期目标是对比不同剂量和来源的w-3脂肪酸对炎症标志物和相关健康指标的潜在影响。具体目的：第一个目的是将海洋型w-3脂肪酸与植物型w-3脂肪酸（EPA + DHA vs. ALA）进行对比。第二个目的是对比两种不同剂量的w-3脂肪酸。选择较低的剂量是为了反映严格从食物来源获得的高但实际的剂量。高剂量将是低剂量的三倍，而且只有在食用食物来源以外的膳食补充剂的情况下才有可能切实实现。设计：本研究采用随机临床试验。100名被发现患有“代谢综合征”、心脏病风险增加的成年人将被随机分配到安慰剂组，或者在八周内服用四种w-3脂肪酸方案中的一种：低EPA/DHA、高EPA/DHA、低ALA或高ALA（即每组20）。将在多个时间点（0,2,4和8周）采集血液样本，以检查补充剂摄入时间对研究结果的影响。主要研究结果为CRP、IL-6、TNF- α和slCAM-1。意义：这种通常安全且相对便宜的饮食方法对心脏病的预防和治疗具有相当大的潜力，但需要更多的信息来了解w-3脂肪酸的最佳剂量和来源，以及哪些特定的炎症标志物可能参与其效果。在这项研究中选择的患有代谢综合征的成年人是那些患心脏病的风险增加的人，也是那些最有可能从不同的治疗方法中受益的人。

DESCRIPTION (provided by applicant): BACKGROUND: A specific type of dietary polyunsaturated fat - omega-3 fatty acids (w-3 FAs) - has been found to be protective of death from cardiovascular disease. There are two general sources of these dietary w-3 FAs: marine sources provide EPA and DHA, and plant food sources provide ALA. These are also widely available as nutritional supplements. Whether one form or the other is more effective in disease prevention remains controversial. Part of the controversy is due to the lack of consensus on optimal doses from the different sources and/or to the different types of people studied. Potential benefits are likely to be increased for those with insulin resistance (the metabolic syndrome) who have elevated levels of both triglycerides and inflammatory markers. LONG TERM OBJECTIVE is to contrast different doses and sources of w-3 FA's for their potential effects on inflammatory markers and related health measures. SPECIFIC AIMS: The first aim is to contrast the marine type w-3 FAs to the plant-based w-3 FAs (EPA + DHA vs. ALA). The second aim is to contrast two doses of each of these types of w-3 FAs. The lower dose has been selected to be reflective of what would be considered a high but realistic dose to obtain strictly from food sources. The higher dose will be 3 times the lower dose and would likely only be realistically achievable if dietary supplements were consumed in addition to food sources. DESIGN: A randomized clinical trial will be employed in this study. One hundred adults found to have the "metabolic syndrome", who are at increased risk of heart disease, will be randomly assigned to either a placebo group, or to take one of four w-3 FA regimens for eight weeks: Low EPA/DHA, High EPA/DHA, Low ALA or High ALA (i.e. 20 per group). Blood samples will be collected at multiple time points (0, 2, 4 and 8 weeks) to examine the effect of the duration of supplement intake on study outcomes. The primary study outcomes are CRP, IL-6, TNF- alpha, and slCAM-1. SIGNIFICANCE: This generally safe and relatively inexpensive dietary approach to heart disease prevention and treatment has considerable potential, but more information is needed regarding optimal doses and sources of w-3 FAs, as well as what particular markers of inflammation may be involved in its effects. The adults with the metabolic syndrome selected for this study are those that are at increased risk of heart disease, and those most likely to be benefit from the different therapies tested.