Alternate day fasting for weight loss, weight maintenance, and cardio-protection

描述（由申请人提供）：超重和肥胖个体患冠心病（CHD）的风险增加。通过限制饮食来减肥可以大大降低患血管疾病的风险。最常见的饮食限制方案是每日卡路里限制（CR）。另一种采用的饮食限制方案，虽然远不常见，是隔天修改禁食（ADMF）。ADMF包括一个“饲料日”，在这个“饲料日”中，食物是随意食用的，与一个“禁食日”交替，在这个“禁食日”中，食物摄入量部分减少。我们为期12周的初步研究结果显示，在治疗8周后，ADMF的依从性超过了CR。增加ADMF的依从性导致更大的体重减轻，从而产生更明显的冠心病风险改善。目前尚不清楚的是，在较长的治疗时间（24周）内，ADMF的依从性是否保持在接近最高水平，以及与CR相比，这种改善的依从性是否会导致体重和冠心病风险的更大降低。一旦体重减轻，体重维持是极其重要的，因为如果体重恢复，冠心病风险可能会增加。ADMF是否是维持体重的有效策略尚不清楚。因此，本提案的目的是：目的1：确定在24周的干预期间，ADMF的依从性大于CR，并确定增加ADMF的依从性是否会导致更大的体重减轻；目的2：与CR相比，24周内ADMF对体重的更大降低将导致传统冠心病风险参数（血压、血脂水平、胆固醇合成率、LDL颗粒大小和CRP）和新出现的冠心病风险参数（脂肪细胞衍生激素、体脂分布和脂肪细胞大小）的更大改善；目的3：确定ADMF是一种有效的饮食疗法，可以维持体重减轻和持续改善冠心病风险指标，并比较ADMF和CR受试者在饮食认知和行为方面的变化。将实施一项52周的随机、对照、平行饲养试验来检验这些目标。试验将分为3个连续干预期：(1)4周基线期；(2)减肥24周，并提供食物；(3) 24周不提供食物的体重维持。体重超重和肥胖受试者（n = 90）随机分为3组：(1)ADMF组，“禁食日”限制75%能量，“采食日”自由采食；(2) CR，每天限制25%；或者3)控制，每天100%的能量摄入。在体重维持阶段，ADMF受试者在“禁食日”消耗其能量需求的25%，在“喂养日”消耗其能量需求的175%，而CR和对照组受试者每天消耗其能量需求的100%。我们的研究结果将表明，ADMF可以作为CR的替代方案，帮助超重和肥胖个体减肥，保持体重减轻，并维持冠心病风险的降低。这项研究还将深入了解ADMF发生的特定行为变化，解释为什么ADMF是一种成功的体重维持饮食策略。

DESCRIPTION (provided by applicant): Overweight and obese individuals are at increased risk for coronary heart disease (CHD). Losing weight by means of dietary restriction greatly reduces vascular disease risk. The most common dietary restriction protocol implemented is daily calorie restriction (CR). Another dietary restriction regimen employed, although far less commonly, is alternate day modified fasting (ADMF). ADMF involves a "feed day" where food is consumed ad-libitum, alternated with a "fast day", where food intake is partially reduced. Results from our 12- week pilot study show that adherence to ADMF exceeds that of CR after 8 weeks of treatment. This increased adherence to ADMF results in greater weight loss, which produces more pronounced improvements in CHD risk. What has yet to be determined is whether adherence to ADMF remains near maximal for longer treatment durations (24 weeks), and if this improved adherence results in greater reductions in body weight and CHD risk, versus CR. Once weight loss is achieved, weight maintenance is extremely important as CHD risk can increase if weight is regained. Whether ADMF is an effective strategy for weight maintenance remains unknown. Accordingly, the aims of this proposal are: Aim 1: To establish that adherence to ADMF is greater than that of CR during a 24-week intervention period and to determine if increased adherence to ADMF results in greater weight loss; Aim 2: To establish that greater reductions in body weight by ADMF over a 24-week period will result in greater improvements in traditional CHD risk parameters (blood pressure, plasma lipid levels, cholesterol synthesis rate, LDL particle size, and CRP) and emerging CHD risk parameters (fat cell- derived hormones, body fat distribution, and fat cell size) in comparison to CR; and Aim 3: To establish that ADMF is an effective diet therapy to maintain weight loss and sustain improvements in CHD risk indicators, and to compare changes in cognitive and behavioral components of eating between ADMF and CR subjects. A 52-week randomized, controlled, parallel-arm feeding trial will be implemented to test these objectives. The trial will be divided into 3 consecutive intervention periods: (1) 4-week baseline; (2) 24-week weight loss with food provided; and (3) 24-week weight maintenance with no food provided. Overweight and obese subjects (n = 90) will be randomized to 1 of 3 groups: (1) ADMF, 75% energy restriction on the "fast day" and ad libitum fed on the "feed day"; (2) CR, 25% restriction everyday; or 3) control, 100% energy intake every day. During the weight maintenance phase, ADMF subjects will consume 25% of their energy needs on the "fast day" and 175% of their needs on the "feed day", while CR and control subjects will consume 100% of their needs every day. Our findings will show that ADMF can be implemented as an alternative to CR to help overweight and obese individuals lose weight, maintain weight loss, and sustain reductions in CHD risk. This study will also generate insights into the specific behavioral changes that occur with ADMF that explain why ADMF is a successful diet strategy for weight maintenance. PUBLIC HEALTH RELEVANCE: The proposed research will demonstrate that alternate day modified fasting (ADMF) is a suitable alternative to daily calorie restriction (CR) for weight loss, weight maintenance, and heart disease prevention. Since many overweight and obese individuals find it difficult to adhere to daily CR, this diet option may improve adherence with these dietary restriction protocols. This, in turn, will allow a greater percent of the overweight and obese population to lose weight, maintain weight loss, and prevent future occurrences of coronary heart disease.