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.

摘要：大约 42% 的美国成年人患有肥胖症，数据表明患有肥胖症的人 肥胖者罹患结直肠癌 (CRC) 的风险增加 30%，因此需要有效的治疗方法。 尽管卡路里摄入量减少，但预防和治疗肥胖将对美国结直肠癌的发病率产生重大影响 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 由于卡路里监测的依从性较低，通过这种方法很难实现减肥，这表明需要 限时饮食（一种间歇性禁食）已被证明会导致癌症。 保护作用，包括降低体重、减少全身炎症和改善血糖 限时饮食是指人们被要求在一个时间内吃完一天的所有食物。 我们最近进行了两次短期禁食。 （≤12周）限时饮食试点研究，评估其安全性和对体重的初步功效 和成人肥胖症的慢性疾病风险标志物我们的结果表明该干预措施是安全且有效的。 此外，还产生了限制时间的饮食。 与基线相比体重减轻约 3%，收缩压、氧化应激和 尽管这些试点研究结果表明限时饮食有望成为治疗胰岛素抵抗的有效工具。 肥胖个体的结直肠癌风险降低，这些数据仍需要强有力的长期证实 目前的建议旨在实施为期12个月（6个月的主动减肥阶段，6个月）。 维持阶段），在 255 名处于升高状态的肥胖成年人（45-65 岁）中进行对照、平行臂试验 CRC 风险受试者将被随机分为 3 组中的一组：1) 限时饮食（减肥阶段：每日广告） 上午 11 点至晚上 7 点随意进食），2）热量限制（减肥阶段：每日 25% 热量限制），或 3）控制（每日随意进食，无进餐时间限制）以比较对以下方面的影响：（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；(4) 维持对体重/成分和系统性/粘膜 CRC 风险的益处 该提案将由具有营养科学专业知识的跨学科团队领导，但有时间限制。 饮食、行为科学、癌症分子标记、胃肠病学和生物统计学。 提案得以实现，将首次表明限时饮食可以作为一种小说来实施 传统节食（即每日热量限制）的替代方案，可控制成人体重并降低结直肠癌风险 拟议的研究也将是第一个也是最全面的分子检查。 介导限时饮食和热量限制的抗癌作用的机制。