Lifestyle, branched-chain amino acids, and cardiovascular risk factors: a randomized trial

生活方式、支链氨基酸和心血管危险因素：一项随机试验

• 批准号: 10728925
• 负责人: Rob M. van Dam
• 金额: $ 12.11万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10728925
• 关键词: Adverse effects; Affect; African American; Animals; Behavioral; Biological; Biological Markers; Blood; Blood Pressure; Body Weight; Body Weight decreased; Branched-Chain Amino Acids; Cardiovascular Diseases; Catabolism; Cessation of life; Cohort Studies; Complement; Counseling; Cross-Sectional Studies; DASH diet; Data; Diet; Dietary Factors; Dietary Fatty Acid; Dietary Practices; Dietary Proteins; Dyslipidemias; Edible Plants; Essential Amino Acids; Female; Genetic study; Health; Hour; Hypertension; Individual; Inflammation; Insulin Resistance; Intake; Intervention; Interview; Isoleucine; Leucine; Life Style; Link; Lipoproteins; Longitudinal Studies; Measurement; Measures; Meat; Mendelian randomization; Morbidity - disease rate; Nitrogen; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome Measure; Overweight; Participant; Pattern; Physical activity; Plants; Plasma; Prevalence; Preventive; Production; Proteins; Randomized; Recommendation; Research; Risk Factors; Sampling; Serum; Therapeutic Intervention; Urine; Valine; Weight Gain; arm; blood lipid; cardiometabolic risk; cardiometabolism; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; diabetes risk; dietary; exercise intensity; experimental study; fitness; fruits and vegetables; glucose metabolism; group intervention; gut microbiota; high risk; improved; indexing; inflammatory marker; insulin sensitivity; intervention effect; lifestyle factors; lifestyle intervention; metabolomics; novel; nutrition; personalized intervention; premature; preventive intervention; protein intake; public health relevance; randomized trial; red meat consumption; repository; targeted treatment; urinary

Abstract Cardiovascular diseases (CVD) are the primary cause of premature death worldwide, and risk factors such as insulin resistance and type 2 diabetes are increasing in prevalence. Therefore, more effective preventive interventions to improve cardiometabolic health are urgently needed. Circulating branched-chain amino acids (BCAA) are strong predictors of type 2 diabetes and CVD. Furthermore, experimental and genetic studies indicate that BCAA overload has adverse cardiometabolic effects. Thus, BCAA levels may be novel targets for preventive interventions. In addition, BCAA levels of individuals may inform personalized interventions. Evidence is accumulating that diet composition, physical activity, and weight loss can reduce plasma BCAA levels by affecting the dietary supply, gut microbiota production, or catabolism of BCAA. However, evidence on the impact of lifestyle factors on BCAA levels is mainly based on small experimental studies and cross- sectional studies. Larger trials and longitudinal studies are crucial to determine whether lifestyle exposures can substantially affect BCAA levels. Furthermore, research on the health consequences of BCAA levels has focused chiefly on the impact of BCAA levels on glucose metabolism, but adverse effects on other CVD risk factors such as inflammation, blood pressure, and dyslipidemia are plausible. The PREMIER study is a randomized trial of the impact of behavioral lifestyle interventions on CVD risk factors with detailed information on diet and physical activity based on interviews and biological measurements. We will measure serum BCAA and other metabolites using targeted quantitative NMR metabolomics in serum samples of 729 participants at baseline and after six months of lifestyle interventions. Our specific aims are as follows: 1). To assess the impact of the randomized lifestyle interventions on circulating BCAA levels over six months. We will evaluate the effect of the ‘established lifestyle intervention,’ including weight loss and increases in physical activity, and the effect of the intervention with added counseling to improve dietary patterns as compared with the control arm. 2). To evaluate specific dietary factors, physical activity, and changes in adiposity in relation to BCAA changes. We will examine changes in physical activity, fitness, protein and BCAA intakes, and healthy plant-based dietary patterns. 3). To evaluate whether changes in BCAA levels affect cardio-metabolic risk factors, including blood lipid profiles, blood pressure, and markers of inflammation and insulin sensitivity. We will also estimate the proportion of the effects of lifestyle changes on cardiovascular risk factors explained by reductions in BCAA levels. Our findings may inform dietary and lifestyle recommendations that consider the impact on BCAA levels.

抽象的 心血管疾病（CVD）是全球过早死亡的主要原因，危险因素（例如 胰岛素抵抗和2型糖尿病的患病率正在增加。因此，更有效的预防性 迫切需要采取干预措施以改善心脏代谢健康。循环的分支链氨基酸 （BCAA）是2型糖尿病和CVD的有力预测指标。此外，实验和遗传研究 表明BCAA过载具有不良心脏代谢效应。那，BCAA水平可能是 预防性干预措施。此外，BCAA水平的个人可能会为个性化的干预提供信息。 有证据表明饮食组成，体育锻炼和体重减轻可以减少血浆BCAA 通过影响饮食供应，肠道菌群产生或BCAA的分解代谢来水平。但是，证据 生活方式因素对BCAA水平的影响主要基于小型实验研究和跨 部分研究。较大的试验和纵向研究对于确定生活方式是否至关重要 暴露会大大影响BCAA水平。此外，对健康后果的研究 BCAA水平集中于BCAA水平对葡萄糖代谢的影响，但对 其他CVD危险因素，例如感染，血压和血脂异常是合理的。总理 研究是对行为生活方式干预对CVD风险因素的影响的随机试验 基于访谈和生物学测量的饮食和体育锻炼信息。我们将衡量 血清BCAA和其他代谢产物使用靶向定量NMR代谢组学中的血清样品729 在基准和六个月的生活方式干预之后，参与者。我们的具体目的如下：1）。到 评估随机生活方式干预措施对六个循环BCAA水平的影响 月份。我们将评估“既定生活方式干预”的影响，包括减肥和 体育锻炼的增加以及通过增加咨询以改善饮食的效果 与对照组相比。 2）。评估特定的饮食因素，体育锻炼和 与BCAA变化有关的肥胖变化。我们将检查体育锻炼，健身， 蛋白质和BCAA摄入量以及健康的植物性饮食模式。 3）。评估是否发生变化 BCAA水平会影响心脏代谢危险因素，包括血脂特征，血压和 炎症和胰岛素敏感性的标记。我们还将估计 心血管危险因素的生活方式改变是通过BCAA水平降低的。我们的发现可能 告知考虑对BCAA水平的影响的饮食和生活方式建议。