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。对于每天的最佳进食次数，目前还缺乏基于证据的建议。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现在大多数人每天进食6-8次的模式。除了可能增加总能量摄入外，频繁进食还会使人处于持续的餐后状态。这种持续的、适度的血糖升高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通路。持续的餐后状态可能会增加全身性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、死亡率和医疗成本的主要原因。为了更好地理解这一现象，我们提出了一项随机交叉临床试验，以测试低EF饮食模式（每天三次进食）与高EF饮食模式（每天六次进食）在炎症、脂肪因子和食欲方面的关系。我们假设，与每天进食三次相比，每天进食六次会增加全身性炎症的生物标志物，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验证我们的假设：1)测试低频率与高频率饮食对炎症生物标志物（空腹高敏c反应蛋白、白细胞介素-6和肿瘤坏死因子- 3）和有益脂肪因子（脂联素）的影响；2)测试低频率与高频率进食对食欲的影响[每日感知食欲评分和六小时食欲测试期间的连续评分]以及参与食欲调节和食物摄入的生物标志物（瘦素、胃饥饿素、肽YY和胆囊收缩素）。我们将招募50名体重正常、超重或肥胖的男性和女性。参与者将按随机顺序完成两个为期3周的等热量干预期[低摄取量（每天3次进食）和高摄取量（每天6次进食）]。参与者将自由生活，使用研究提供的结构化膳食计划吃自己的食物。研究人员将提供持续的支持和指导，以最大限度地遵守协议。空腹血样将在每个研究阶段的开始和结束时采集。我们将通过使用线性回归的GEE修正来测试干预效果，以比较每个研究阶段的平均生物标志物反应（干预效果）。在每个干预期的最后一天，参与者将完成6小时的食欲测试，在低食欲阶段提供两顿测试餐，在高食欲阶段提供四顿测试餐。将收集连续食欲评分和血液来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形成在整体健康饮食背景下进食频率的指导方针。

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.