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) 是全世界过早死亡的主要原因，危险因素包括 胰岛素抵抗和2型糖尿病的患病率正在增加，因此，更有效的预防措施。 迫切需要改善心脏代谢健康的干预措施。 (BCAA) 是 2 型糖尿病和 CVD 的强有力的预测因素。此外，实验和遗传学研究。 表明 BCAA 过载会对心脏代谢产生不利影响，因此，BCAA 水平可能是新的目标。 此外，个体的支链氨基酸水平可以为个性化干预提供信息。 越来越多的证据表明饮食结构、体力活动和减肥可以降低血浆支链氨基酸 然而，有证据表明，BCAA 会影响膳食供应、肠道微生物群的产生或分解代谢。 生活方式因素对 BCAA 水平的影响主要基于小型实验研究和交叉研究 更大规模的试验和纵向研究对于确定生活方式是否重要至关重要。 此外，对支链氨基酸的健康影响的研究表明，接触支链氨基酸会严重影响支链氨基酸的水平。 支链氨基酸水平主要关注支链氨基酸水平对葡萄糖代谢的影响，但对 其他心血管疾病危险因素，如炎症、血压和血脂异常也是可能的。 该研究是一项关于行为生活方式干预对 CVD 危险因素影响的随机试验，详细介绍了 我们将根据访谈和生物测量来测量有关饮食和身体活动的信息。 使用靶向定量 NMR 代谢组学对 729 份血清样本中的血清 BCAA 和其他代谢物进行分析 基线和六个月生活方式干预后的参与者我们的具体目标如下： 1)。 评估随机生活方式干预对六岁以上循环支链氨基酸水平的影响 我们将评估“既定生活方式干预”的效果，包括减肥和 体力活动的增加，以及通过增加咨询来改善饮食的干预效果 与对照组相比的模式2)。 与 BCAA 变化相关的肥胖变化我们将检查体力活动、健康状况的变化， 评估蛋白质和支链氨基酸的摄入量以及健康的植物性饮食模式是否发生变化。 BCAA 水平影响心脏代谢危险因素，包括血脂、血压和 我们还将估计炎症和胰岛素敏感性的影响比例。 我们的研究结果可能是通过支链氨基酸水平的降低来解释生活方式的改变对心血管危险因素的影响。 提供考虑对 BCAA 水平影响的饮食和生活方式建议。