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

描述（由申请人提供）：建议超重和肥胖个体减轻体重以预防癌症;然而，体重减轻，特别是老年人，可能导致有害的加速骨和肌肉损失。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。在一些流行病学研究中，维生素D和循环维生素D代谢物的较高膳食摄入量与结肠癌，乳腺癌和其他癌症的风险呈负相关，但不是全部。除了其在骨代谢中的公认作用外，维生素D还具有抗脂肪形成的特性，可以防止体重增加，并与肌肉力量和身体功能呈正相关，这可以支持采用与降低癌症风险相关的生活方式行为，如运动。肥胖和血清维生素D水平之间存在一致的负相关性，这表明超重或维生素D水平与癌症风险之间的某些关联可能是由于它们彼此之间的关系。然而，维生素D和身体组成的特定成分之间的关系尚未在老年人群中得到很好的表征。同样，维生素D水平是否会影响通过饮食和运动减肥的个体的脂肪，肌肉和骨量尚不清楚。本提案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的效果（胆钙化醇）补充（每日2000 IU）与安慰剂相比，对身体组成变化的影响，包括总脂肪量和躯干脂肪量（kg）、%体脂、总瘦体重和非瘦体重（kg）、%瘦体重、骨矿物质含量（g），和脊柱和髋部的骨矿物质密度（BMD）（g/cm 2），在228名超重/肥胖的绝经后妇女（50-75岁）中，通过热量限制和有氧运动进行12个月的生活方式改变减肥计划。次要目标是：1）检查身体成分的变化在多大程度上介导了血清维生素D与母体RCT中检测的癌症风险生物标志物（胰岛素抵抗和C反应蛋白[CRP]）之间的相关性; 2）检查身体成分变化与其他结果（如力量、胰岛素抵抗和CRP）变化之间的相关性。虽然父母试验正在测试对体重和BMI的影响， 它不能确定有多少变化是由于身体组成的特定成分造成的，而身体组成的特定成分是理解能量平衡和癌症之间联系机制的主要重要数据。这项拟议的研究非常新颖，因为之前没有随机对照试验测试过维生素D补充是否可以改善体重减轻对正在减肥的绝经后妇女肌肉和骨质的潜在不良影响。鉴于老年人超重/肥胖和维生素D水平低的高患病率和相关健康风险，本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且易于采用的癌症预防干预措施。 公共卫生相关性：我们将在一项正在进行的随机试验的背景下，确定口服维生素D补充剂（每日2000 IU）与安慰剂相比，对由于超重和肥胖以及维生素D水平低而导致几种癌症风险增加的绝经后妇女的身体组成变化（脂肪、瘦肉和骨量）的影响。

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. PUBLIC HEALTH RELEVANCE: We will determine, within the context of an ongoing randomized trial, the effect of oral vitamin D supplementation (2000 IU daily) vs. placebo on body composition changes (fat, lean, and bone mass) measured by dual x-ray absorptiometry (DXA) in postmenopausal women who are at increased risk for several cancers by virtue of being overweight and obese and having low levels of vitamin D.