Vitamin D Effect on Body Composition During Behavioral Weight Loss in Women

描述(由申请人提供)：建议超重和肥胖的人减肥以预防癌症；然而，减肥，特别是老年人的减肥，可能会导致有害的加速骨骼和肌肉流失。越来越多的证据表明，维生素D通过调节细胞生长和凋亡以及减少血管生成而具有抗癌作用。在一些(但不是全部)流行病学研究中，较高的维生素D饮食摄入量和循环中的维生素D代谢物与患结肠癌、乳腺癌和其他癌症的风险呈负相关。除了公认的骨骼代谢作用外，维生素D还具有抗脂肪作用，可以防止体重增加，并与肌肉力量和身体功能呈正相关，这可能支持采取与降低癌症风险相关的生活方式，如锻炼。肥胖和血清维生素D水平之间存在一致的负关联，这表明超重或维生素D水平与癌症风险之间的一些关联可能是由于它们之间的相互关系。然而，在老年人群中，维生素D和身体成分的特定成分之间的关系还没有得到很好的描述。同样，维生素D水平是否影响通过饮食和锻炼减肥的个体的脂肪、肌肉和骨量尚不清楚。这项建议的主要具体目的是，在正在进行的双盲随机对照试验(RCT)的背景下，确定口服维生素D3(胆钙素)补充(每天2000IU)与安慰剂对身体成分变化的影响，包括总和躯干脂肪质量(公斤)、体脂百分比、总和附件瘦质量(公斤)、瘦质量百分比、骨矿含量(G)和脊柱和臀部的骨密度(g/cm2)。在228名超重/肥胖的绝经后妇女(50-75岁)中，接受为期12个月的生活方式改变计划，通过限制热量和有氧运动来减肥。第二个目标是：1)检查身体成分的变化在多大程度上中介血清维生素D和母体RCT(胰岛素抵抗和C反应蛋白[CRP])检测的癌症风险生物标记物之间的关联；以及2)检查身体成分的变化与其他结果(如力量、胰岛素抵抗和CRP)变化之间的关系。虽然家长试验正在测试对体重和BMI的影响， 它无法确定这种变化在多大程度上是由于身体成分的特定成分造成的，这些成分代表了理解能量平衡和癌症联系机制的主要重要数据。这项拟议的研究具有很高的新颖性，因为以前的RCT没有测试过维生素D补充是否可以改善减肥对绝经后减肥妇女肌肉和骨量的潜在不利影响。鉴于老年人超重/肥胖和维生素D缺乏的高患病率和相关的健康风险，这项研究的结果将对临床和公共卫生实践产生直接影响，并可能导致相对简单和容易采用的癌症预防干预措施。

DESCRIPTION (provided by applicant): Weight loss for overweight and obese individuals is recommended for cancer prevention; however, weight loss, particularly in older adults, can cause deleterious accelerated bone and muscle loss. A growing body of evidence suggests that vitamin D has anti-carcinogenic effects by modulating cellular growth and apoptosis, and by reducing angiogenesis. Higher dietary intake of vitamin D and circulating vitamin D metabolites have been inversely associated with risk of colon, breast and other cancers in some, but not all, epidemiological studies. In addition to its well-recognized role in bone metabolism, vitamin D also has anti-adipogenic properties which could protect against weight gain, and is positively associated with muscle strength and physical functioning, which could support the adoption of lifestyle behaviors associated with reduced cancer risk, such as exercise. A consistent inverse association is observed between obesity and serum vitamin D level which suggests that some of the associations between excess body weight or vitamin D levels with cancer risk could be due to their relationship with each other. However, the relationships between vitamin D and specific components of body composition have not been well characterized in older populations. Likewise, whether vitamin D level influences fat, muscle, and bone mass in individuals undergoing weight loss through diet and exercise is unclear. The primary Specific Aim of this proposal is to determine, within the context of an ongoing double-blind randomized controlled trial (RCT), the effect of oral vitamin D3 (cholecalciferol) supplementation (2000 IU daily) vs. placebo on body composition changes, including total and trunk fat mass (kg), % body fat, total and appendicular lean mass (kg), % lean mass, bone mineral content (g), and bone mineral density (BMD) at the spine and hip (g/cm2), in 228 overweight/obese postmenopausal women (50-75 y) undergoing a 12-month lifestyle change weight loss program through caloric restriction and aerobic exercise. Secondary aims are to: 1) examine the extent to which changes in body composition mediate associations between serum vitamin D and biomarkers of cancer risk tested in the parent RCT (insulin resistance and C-reactive protein [CRP]); and 2) examine associations between change in body composition and change in other outcomes such as strength, insulin resistance, and CRP. While the parent trial is testing effects on weight and BMI, it cannot determine how much of the change is due to specific components of body composition, which represents data of principal importance in understanding the mechanisms linking energy balance and cancer. The proposed study is highly novel as no previous RCT has tested whether vitamin D repletion can ameliorate potential adverse effects of weight loss on muscle and bone mass in postmenopausal women undergoing weight loss. Given the high prevalence and associated health risks of overweight/obesity and low vitamin D status among older adults, results of this study will have direct implications for clinical and public health practice and coud lead to a relatively simple and easily adopted intervention for cancer prevention.