Supplementary Material for Peer Review.docx

This study investigated how changes in branched-chain amino acid (BCAA) levels affect cardiovascular disease (CVD) risk factors over time. Using data from 708 adults in the U.S. PREMIER lifestyle trial, researchers measured BCAA levels and cardiometabolic biomarkers at baseline and again after six months. Participants had received either general or intensive lifestyle counseling. The findings showed that increases in BCAA levels were significantly associated with greater insulin resistance, inflammation (measured by GlycA), ApoB, and VLDL-cholesterol, key markers linked to CVD. Interestingly, the effects on HDL and triglycerides varied by the type of BCAA (valine, leucine, or isoleucine). No associations were found with fasting glucose or blood pressure. These results suggest that rising BCAA levels may contribute to CVD risk by worsening metabolic and lipid profiles, highlighting the need for further research on the role of individual BCAAs in heart health.