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

> **NIH NIH R21** · GEORGE WASHINGTON UNIVERSITY · 2024 · $121,125

## Abstract

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.

## Key facts

- **NIH application ID:** 10907792
- **Project number:** 5R21HL169803-02
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Rob M. van Dam
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $121,125
- **Award type:** 5
- **Project period:** 2023-08-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907792

## Citation

> US National Institutes of Health, RePORTER application 10907792, Lifestyle, branched-chain amino acids, and cardiovascular risk factors: a randomized trial (5R21HL169803-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10907792. Licensed CC0.

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