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。通过饮食限制减肥可以大大降低血管疾病的风险。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禁食（ADMF），尽管不太常见。ADMF涉及“进食日”，在该日，食物自由进食，与“禁食日”交替，在该日，食物摄入量部分减少。我们12周的初步研究结果表明，治疗8周后，ADMF的依从性超过CR。这种增加的ADMF依从性导致更大的体重减轻，从而产生更明显的CHD风险改善。目前尚不确定的是，与CR相比，ADMF的依从性是否在更长的治疗持续时间（24周）内保持接近最大值，以及这种依从性的改善是否会导致体重和CHD风险的更大降低。一旦体重减轻，体重维持是非常重要的，因为如果体重恢复，CHD风险会增加。ADMF是否是维持体重的有效策略仍不清楚。因此，本提案的目的是：目的1：确定在24周干预期间，ADMF依从性大于CR依从性，并确定ADMF依从性的增加是否会导致更大的体重减轻;目的2：确定ADMF在24周内更大程度地降低体重将导致传统CHD风险参数的更大改善（血压、血脂水平、胆固醇合成率、LDL颗粒大小和CRP）和新出现的CHD风险参数（脂肪细胞衍生的激素、体脂分布和脂肪细胞大小）;以及目标3：为了确定ADMF是一种有效的饮食疗法，以维持体重减轻和冠心病风险指标的持续改善，并比较ADMF和CR受试者之间进食的认知和行为成分的变化。将实施一项为期52周的随机、对照、平行臂喂养试验来测试这些目标。试验将分为3个连续干预阶段：（1）4周基线;（2）24周体重减轻，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）将随机分配至3组之一：（1）ADMF，“禁食日”限制75%能量摄入，“进食日”随意进食;（2）CR，每天限制25%能量摄入;或3）对照，每天100%能量摄入。在体重维持阶段，ADMF受试者将在“禁食日”消耗其能量需求的25%，在“进食日”消耗其能量需求的175%，而CR和对照受试者将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，保持减肥效果，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是维持体重的成功饮食策略。 公共卫生相关性：拟议的研究将证明隔日改良禁食（ADMF）是每日卡路里限制（CR）的合适替代方案，用于减肥，体重维持和预防心脏病。由于许多超重和肥胖的人发现很难坚持每日CR，这种饮食选择可能会提高这些饮食限制协议的依从性。反过来，这将使更大比例的超重和肥胖人群减肥，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.