Eating frequency and its influence on satiety and biomarkers of health & disease

描述（由申请人提供）：本提案将调查进食频率是否影响健康。缺乏基于证据的建议，以确定每日进食的最佳次数。这是一个重要的研究领域，因为在过去的40年里，美国人的饮食习惯已经从一日三餐转变为大多数人现在每天有6-8次进食的模式。除了潜在的总能量摄入增加，频繁进食会使人们处于恒定的餐后状态。这种持续的、适度升高的胰岛素水平扰乱了正常的葡萄糖-胰岛素和反调节激素网络平衡，也扰乱了下游细胞信号传导途径。恒定的餐后状态可能会增加全身炎症并引起许多其他代谢紊乱。因此，进食频率（EF）可能与饮食相关慢性疾病的风险有关，如心血管疾病，癌症和糖尿病，这些疾病是美国发病率，死亡率和医疗保健费用的主要原因。交叉临床试验，以测试低EF饮食模式（三次进食场合/天）与高EF进食模式（六次进食场合/天）在炎症、脂肪因子和食欲方面的比较。我们假设，与每天吃三次相比，每天吃六次会增加全身炎症的生物标志物，减少有益的脂肪因子，并增加生物标志物和自我报告的食欲指标。我们将通过以下具体目标来检验我们的假设：1）检验低进食频率与高进食频率对炎症生物标志物的影响（空腹高敏C反应蛋白，白细胞介素-6和肿瘤坏死因子-β）和有益的脂肪因子（脂联素）; 2）为了测试低与高进食频率对食欲的影响[在六个月的时间里，小时食欲测试期]和参与食欲调节和食物摄入的生物标志物（瘦素、生长素释放肽、肽YY和胆囊收缩素）。我们将招募n=50名体重正常、超重或肥胖的男性和女性。受试者将以随机顺序完成两个为期3周的等热量干预期[低EF（每天3次进食）和高EF（每天6次进食）]。受试者将自由生活，并使用研究提供的结构化膳食计划吃自己的食物。研究工作人员将提供持续支持和指导，以最大限度地遵守方案。将在每个研究阶段开始和结束时采集空腹血样。我们将通过使用线性回归的GEE修改来比较每个研究阶段的平均生物标志物应答（干预效应），从而检验干预效应。在每个干预阶段的最后一天，受试者将完成6小时的食欲测试，其中在低EF阶段提供两次测试餐，在高EF阶段提供四次测试餐。将收集系列食欲评级和血液以评估感知食欲和食欲和饱腹感的激素。这项调查的结果将用于制定在整体健康饮食背景下的饮食频率指南。

DESCRIPTION (provided by applicant): This proposal will investigate whether eating frequency influences health. Evidence-based recommendations are lacking for the optimal number of daily eating occasions. This is an important area of research because over the past 40 years Americans' eating habits have changed from three meals a day to a pattern whereby most people now have 6-8 daily eating occasions. Apart from potential increases in total energy intake, frequent eating leaves people in a constant postprandial state. This constant, modestly elevated glycemia disturbs the normal glucose-insulin and counter-regulatory hormone network balance and also disturbs downstream cell signaling pathways. A constant postprandial state may increase systemic inflammation and cause numerous other metabolic disturbances. As a result, eating frequency (EF) may be associated with risk of diet-related chronic diseases such as cardiovascular disease, cancer and diabetes, which are the major causes of morbidity, mortality and health care costs in the U.S. To better understand this phenomena we propose a randomized, cross-over clinical trial to test a low-EF eating pattern (three eating occasions/day) vs. a high-EF eating pattern (six eating occasions/day) in relation to inflammation, an adipokine and appetite. We hypothesize that compared to eating three times/day, eating six times/day will increase biomarkers of systemic inflammation, will decrease a beneficial adipokine and will increase both biomarkers and self-reported measures of appetite. We will test our hypothesis with these specific aims: 1) To test the effects of low vs. high eating frequency on inflammatory biomarkers (fasting high-sensitivity C-reactive protein, Interleukin-6 and tumor necrosis factor-�,) and a beneficial adipokine (adiponectin); 2) To test the effects of low vs. high eating frequency on appetite [daily ratings of perceived appetite and serial ratings during a six-hour appetite testing session] and biomarkers involved in appetite regulation and food intake (leptin, ghrelin, peptide YY, and cholecystokinin). We will enroll n=50 males and females who are normal weight, overweight or obese. Participants will complete two 3-week long isocaloric intervention periods in random order [low EF (three eating occasions/day) and high EF (six eating occasions/day)]. Participants will be free-living and eating their own food using study-provided structured meals plans. Study staff will provide on-going support and instruction to maximize adherence to the protocol. Fasting blood samples will be collected at the beginning and end of each study phase. We will test for the intervention effect by using the GEE modification of linear regression to compare mean biomarker response (intervention effect) for each study phase. On the last day of each intervention period, participants will complete 6-hour appetite testing sessions where two test meals will be provided in the low-EF phase and four test meals will be provided in the high-EF phase. Serial appetite ratings and bloods will be collected to assess perceived appetite and hormones of appetite and satiety. Results from this investigation will be used to form guidelines for eating frequency in the context of an overall healthy diet.