Vascular Consequences of Ultra-Processed Foods in Middle-Aged Adults

项目摘要 年龄是心血管疾病（CVD）的主要危险因素，年龄相关的血管功能障碍被认为是 连接两者的关键过程。中年是特别脆弱的时期，当风险因素超过诊断 CVD的阈值和临床表现首先变得明显。超加工食品（UPF）占近60% 标准美国饮食（SAD）中的总能量。观察性研究的结果表明，UPF 消费增加CVD风险，与整体饮食质量无关（即，饱和脂肪、钠、糖和膳食 纤维摄入量）。“工业化微生物群”可能将饮食，特别是UPF，与炎症和CVD的增加联系起来， 中年人。高UPF摄入量增加了心脏年龄超过10岁的可能性， 中年人亚临床冠状动脉粥样硬化的风险。然而，减少UPF消费的影响 对中年人血管功能的影响尚不清楚。本R21提案的总体目标是建立 中年人UPF消耗减少后血管功能改善的概念验证 成年人，以便在未来进行更大，更全面和更机械的试验。为此，继A 2-34名健康中年人（45-64岁）将完成为期4周的正常热量导入饮食（60%UPF的SAD）， SAD和未加工/最低限度加工食品（0% UPF）的随机交叉试验。2周洗脱期 (same SAD导入饮食）将分开治疗。受试者将被喂食一种正常热量的饮食（50%碳水化合物，35%碳水化合物）。 脂肪，15%蛋白质），与膳食纤维、添加糖、饱和脂肪、单不饱和脂肪和多不饱和脂肪、钠、预 以及益生菌、微量营养素和整体饮食质量，以避免潜在的混淆， 体重变化和其他可能影响研究结果的饮食因素。研究的商业添加剂含量 将对饮食进行定量，并通过化学分析验证研究饮食组成。流量测量- 介导的扩张，动脉僵硬度，肠道微生物群组成/功能，粪便短链脂肪酸（SCFA），肠 炎症、肠通透性、血清内毒素和炎性细胞因子将在 每个4周治疗期。这项创新的研究将由一个既定的调查小组进行， 丰富的经验和良好的成功记录进行良好控制的饮食干预研究， 老化和CVD风险。

Project Summary Age is the primary risk factor for cardiovascular disease (CVD) and age-related vascular dysfunction is considered the key process linking the two. Middle age is particularly vulnerable period when risk factors exceed diagnostic thresholds and clinical expression of CVD first becomes evident. Ultra-processed foods (UPF) comprise almost 60% of total energy in the standard American diet (SAD). The results of observational studies suggest that UPF consumption increases CVD risk, independent of overall diet quality (i.e., saturated fat, sodium, sugar, and dietary fiber intake). The “industrialized microbiota” may link diet, particularly UPF, to increased inflammation and CVD in middle-aged adults. High intake of UPF increases the likelihood of an excess heart age >10years and doubles the risk of subclinical coronary atherosclerosis in middle-aged adults. However, the impact of reducing UPF consumption on vascular function in middle-aged adults is unknown. The overall objective of this R21 proposal is to establish proof-of-concept for an improvement in vascular function following reductions in UPF consumption in middle-aged adults, in order to conduct a larger, more comprehensive and mechanistic trial in the future. To this end, following a 2-week eucaloric lead-in diet (SAD with 60% UPF), 34 healthy middle-aged adults (45-64 yrs) will complete a 4-week randomized crossover trial of both a SAD and an un/minimally processed foods (0% UPF). A 2-week washout period (same SAD lead-in diet) will separate the treatments. Participants will be fed a eucaloric diet (50% carbohydrate, 35% fat, 15% protein) matched for dietary fiber, added sugars, saturated fat, mono- and poly-unsaturated fat, sodium, pre- and probiotics, micronutrients, and overall diet quality, for the duration of the study to avoid potential confounds of weight change and other dietary factors which may influence study outcomes. Commercial additive content of study diets will be quantified, and study diet composition will be verified by chemical analysis. Measurements of flow- mediated dilation, arterial stiffness, gut microbiota composition/function, fecal short chain fatty acids (SCFA), intestinal inflammation, intestinal permeability, serum endotoxin, and inflammatory cytokines will be made before and following each 4-week treatment period. This innovative study will be conducted by an established investigative team with extensive experience and a strong record of success performing well-controlled dietary intervention studies targeting aging and CVD risk.