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

描述(由申请人提供)：超重和肥胖的人患冠心病的风险增加。通过限制饮食来减肥，大大降低了患血管疾病的风险。最常见的饮食限制方案是每日卡路里限制(CR)。另一种饮食限制方案是隔日改良式禁食(ADMF)，尽管不太常见。ADMF包括“喂食日”和“禁食日”交替进行，在“喂食日”中，食物的摄入量会部分减少。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。这增加了对ADMF的坚持，导致了更大的体重减轻，从而产生了更显著的CHD风险改善。尚未确定的是，在更长的治疗时间(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，这种依从性的改善是否会导致体重和冠心病风险的更大降低。一旦实现减肥，保持体重是极其重要的，因为如果体重恢复，冠心病的风险可能会增加。ADMF是否是一种有效的体重维持策略仍不清楚。因此，这项建议的目的是：目标1：确定在24周干预期内ADMF的依从性大于CR，并确定ADMF的依从性增加是否会导致更大的体重减轻；目标2：确定与CR相比，ADMF在24周内更大程度地减轻体重将导致传统的CHD风险参数(血压、血浆脂质水平、胆固醇合成率、低密度脂蛋白颗粒大小和CRP)和新出现的CHD风险参数(脂肪细胞衍生激素、身体脂肪分布和脂肪细胞大小)的改善；目的3：确定ADMF是维持体重减轻和CHD风险指标持续改善的有效饮食疗法，并比较ADMF和CR受试者在进食认知和行为成分方面的变化。将实施一项为期52周的随机、对照、平行手臂喂养试验来测试这些目标。试验将分为三个连续的干预期：(1)4周基线；(2)24周减肥，提供食物；(3)24周体重维持，不提供食物。超重和肥胖受试者(n=90)将被随机分为3组：(1)ADMF组，禁食日限制75%能量摄入，自由采食日喂养；(2)CR组，每天限制25%能量摄入；或(3)对照组，每天100%能量摄入。在体重维持阶段，ADMF受试者每天将消耗其能量需求的25%和175%，而CR和对照组受试者每天将消耗其所需能量的100%。我们的研究结果将表明，ADMF可以作为CR的替代方案，帮助超重和肥胖者减肥，保持减肥，并持续降低CHD风险。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。 公共卫生相关性：拟议的研究将证明，在减肥、保持体重和预防心脏病方面，隔日修改禁食(ADMF)是每日热量限制(CR)的合适替代方案。由于许多超重和肥胖的人发现很难坚持每天的CR，这种饮食选择可能会改善对这些饮食限制方案的遵守。反过来，这将使更多的超重和肥胖人口减轻体重，保持减肥，并防止未来发生冠心病。

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.