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: 10304332
• 负责人: Lisa Tussing-Humphreys
• 金额: $ 86.12万
• 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 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10304332
• 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; Down-Regulation; Eating; Environmental Exposure; Epigenetic Process; Food; Gastroenterology; Gene Expression; Gene Expression Profile; Genes; Genetic; Health; Heredity; Hour; Immune; Immune System Diseases; Incidence; Individual; Inflammation; 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; Randomized; Research; Risk; Risk Factors; Risk Marker; Risk Reduction; Safety; Specific qualifier value; Study Subject; 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; 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％的美国成年人口肥胖，数据表明患有 肥胖症患结直肠癌（CRC）的风险高30％。因此，有效的方法 防止和治疗肥胖将对美国的CRC事件产生重大影响，尽管卡路里 通过生活方式干预的限制是治疗肥胖，临床意义的最常见方法 由于对卡路里监测的依从性较低，因此很难通过这种方法实现体重减轻，这表明需要 进行创新。在动物中显示了时间限制的饮食，一种间歇性禁食，以赋予癌症 保护作用，包括降低体重，减少全身注射和改善葡萄糖 代谢。时间限制的饮食是要求个人在一天内食用所有食物的地方 指定的时间范围，并在一天中剩余的几个小时内快速水。我们最近进行了两次短期 （≤12周）对时间限制饮食的试点研究，以评估其体重的安全性和初步效率 肥胖成年人的慢性疾病风险标志物。我们的结果表明，干预是安全的 肥胖成年人体重减轻的可接受方法。而且，生产时间限制的饮食 基线的体重减轻约3％，收缩压，氧化应激和 胰岛素抵抗。尽管这些试点调查结果显示出有望饮食作为有效工具的希望 肥胖个体的CRC风险降低，这些数据仍然需要通过良好动力的长期确认 临床试验。本提案旨在实施12个月（6个月的活跃减肥阶段，6个月） 维护阶段），255名肥胖成年人（45-65岁）的受控，平行的ARM试验 CRC风险。受试者将随机分为3组中的1个：1）时间限制的饮食（减肥阶段：每日广告 从上午11点至晚上7点开始摄入量），2）卡路里限制（减肥阶段：每天25％卡路里限制）或 3）控制（每日自发食物摄入量，没有餐时限制），以比较：（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 - 相关的生物标志物； （3）结肠粘膜基因表达谱和粘膜注射，DNA损伤和 细胞生长； （4）维持体重/成分和全身/粘膜CRC风险的福利 标记。该建议将由具有营养科学专业知识的跨学科团队领导， 饮食，行为科学，癌症的分子标记，胃肠病学和生物统计学。如果目的 提出了建议，它将首次显示时间限制的饮食可以作为小说实施 替代传统节食（即每日卡路里限制），以减轻体重控制和CRC风险降低 肥胖。拟议的研究也将是对分子的首次也是最全面的检查 介导时间限制饮食和卡路里限制的抗癌作用的机制。