Effects of Time-restricted Eating versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers among Adults with Obesity

限时饮食与每日持续热量限制对肥胖成人体重和结直肠癌风险标志物的影响

• 批准号: 10676824
• 负责人: Lisa Tussing-Humphreys
• 金额: $ 30.17万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676824
• 关键词: Address; Adenomatous Polyps; Adherence; Adult; Affect; American; Animals; Apoptosis; Behavioral Sciences; Biological; Biological Markers; Biometry; Blood; Blood Pressure; Body Composition; Body Weight; Body Weight decreased; Body fat; Body mass index; Caloric Restriction; Calories; Cancer Etiology; Cessation of life; Chronic Disease; Clinical; Clinical Research; Clinical Trials; Colon; Colorectal Cancer; Consumption; DNA Damage; Data; Development; Diagnosis; Differentiation Antigens; Disease; Eating; Environmental Exposure; Epigenetic Process; Food; Gastroenterology; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genetic; Health; Heredity; Hour; Immune; Immune System Diseases; Incidence; Individual; Inflammation; Inflammatory; Insulin Resistance; Insulin-Like Growth Factor I; Interleukin-6; Intermittent fasting; Intervention; Isoprostanes; Life Style; Link; Maintenance; Malignant Neoplasms; Mediating; Metabolic; Metabolic dysfunction; Methods; Molecular; Monitor; Mucositis; Mucous Membrane; Mutation; National Cancer Institute; Nutritional Science; Obesity; Oxidative Stress; Pathway interactions; Persons; Phase; Pilot Projects; Population; Process; Proliferating; Randomized; Research; Risk; Risk Factors; Risk Marker; Risk Reduction; Safety; Specific qualifier value; Testing; Thinness; Time; Time-restricted feeding; Tissues; United States; Up-Regulation; Water; Weight; Weight maintenance regimen; adult obesity; anti-cancer; arm; cancer biomarkers; cell growth; circulating biomarkers; colon carcinogenesis; colon tumorigenesis; colorectal cancer risk; common treatment; cytokine; dieting; effective therapy; experience; feasibility testing; gene repression; glucose metabolism; human old age (65+); improved; inflammatory marker; innovation; lifestyle intervention; modifiable lifestyle factors; modifiable risk; molecular marker; muscle form; novel; obese person; obesity treatment; prevent; protective effect; reduced food intake; systemic inflammatory response; tool

ABSTRACT. Approximately 42% of the U.S. adult population is obese and data suggests that persons with obesity are at a 30% greater risk of developing colorectal cancer (CRC). Therefore, efficacious approaches to preventing and treating obesity will have significant effects on CRC incidence in the U.S. Although calorie restriction through lifestyle intervention is the most common approach to treat obesity, clinically meaningful weight loss is difficult to achieve via this method due to low adherence with calorie monitoring, indicating a need for innovation. Time-restricted eating, a type of intermittent fasting, has been shown in animals to impart cancer protective effects including lower body weight, decreased systemic inflammation, and improved glucose metabolism. Time-restricted eating is where individuals are asked to consume all their food for the day within a specified time frame, and water fast for the remaining hours of the day. We recently performed two short-term (≤12-weeks) pilot studies of time-restricted eating to evaluate its safety and preliminary efficacy on body weight and chronic disease risk markers in adults with obesity. Our results show the intervention is a safe and acceptable approach to weight loss among obese adults. Moreover, time-restricted eating produced approximately 3% weight loss from baseline and reductions in systolic blood pressure, oxidative stress and insulin resistance. Although these pilot findings show promise for time-restricted eating as an effective tool for CRC risk reduction among obese individuals, these data still require confirmation by a well powered longer-term clinical trial. The present proposal aims to implement a 12-month (6-month active weight loss phase, 6-month maintenance phase), controlled, parallel arm trial among 255 obese adults (45-65 years old) who are at elevated CRC risk. Subjects will be randomized to 1 of 3 groups: 1) Time-restricted eating (weight loss phase: daily ad libitum food intake from 11am – 7pm), 2) Calorie restriction (weight loss phase: daily 25% calorie restriction), or 3) Control (daily ad libitum food intake, no meal timing restrictions) to compare the effects on: (1) Body weight, body composition, and intervention adherence; (2) Circulating metabolic, inflammation, and oxidative stress- related biomarkers; (3) Colonic mucosal gene expression profiles and mucosal inflammation, DNA damage and cellular growth; and (4) maintenance of benefits on body weight/composition and systemic/mucosal CRC risk markers. This proposal will be led by a transdisciplinary team with expertise in nutrition science, time-restricted eating, behavioral science, molecular markers of cancer, gastroenterology, and biostatistics. If the aims of this proposal are achieved, it will show for the first time that time-restricted eating can be implemented as a novel alternative to traditional dieting (i.e., daily calorie restriction) for weight control and CRC risk reduction in adults with obesity. The proposed study will also be the first and most comprehensive examination of molecular mechanisms that mediate the anticancer effects of time-restricted eating and calorie restriction.

抽象的。大约42%的美国成年人口患有肥胖症，数据表明，患有肥胖症的人 肥胖患结直肠癌(CRC)的风险要高出30%。因此，有效的方法是 预防和治疗肥胖症将对美国的CRC发病率产生重大影响，尽管卡路里 通过生活方式干预进行限制是治疗肥胖最常见的方法，具有临床意义 通过这种方法很难实现减肥，因为对卡路里监测的依从性较低，这表明需要 为了创新。限时进食是一种间歇性禁食，已经在动物身上被证明会引发癌症 保护作用包括减轻体重、减少全身炎症和改善血糖 新陈代谢。限时进食是指每个人被要求在一天内吃完一天的所有食物 规定的时间范围，一天中剩下的几个小时禁水。我们最近表演了两个短期的 (≤12-Week)限时进食的试点研究，以评估其安全性和对体重的初步疗效 肥胖成年人的慢性病风险标记物。我们的结果表明干预是一种安全和 肥胖成年人可接受的减肥方法。此外，限时进食产生了 体重较基线下降约3%，收缩压、氧化应激和 胰岛素抵抗。尽管这些试点研究结果显示，限时进食是一种有效的治疗方法 肥胖者的结直肠癌风险降低，这些数据仍然需要有良好的长期动力来证实 临床试验。目前的提议旨在实施为期12个月(6个月)的积极减肥阶段，为期6个月 在255名处于高位的肥胖成年人(45-65岁)中进行的对照平行手臂试验 CRC风险。受试者将被随机分为3组：1)限时进食(减肥阶段：每日广告 Libitum食物摄入量从上午11点到晚上7点)，2)卡路里限制(减肥阶段：每天25%卡路里限制)，或 3)对照(每天随意进食，不限制进餐时间)，比较它们对以下方面的影响：(1)体重， 身体成分和干预依从性；(2)循环代谢、炎症和氧化应激- 相关生物标志物；(3)结肠粘膜基因表达谱与粘膜炎症、DNA损伤和 细胞生长；以及(4)维持对体重/成分和全身/粘膜结直肠癌风险的益处 记号笔。这项提议将由一个在营养科学方面具有专业知识的跨学科团队领导，时间有限。 饮食、行为科学、癌症分子标记物、胃肠病学和生物统计学。如果这样做的目的是 这将首次表明，限时进食可以作为一种新颖的方式来实施 成人控制体重和降低结直肠癌风险的传统节食(即限制每日卡路里)的替代方案 与肥胖有关。这项拟议的研究也将是第一次也是最全面的分子检测 限时进食和卡路里限制的抗癌作用机制。