Dietary Branched-Chain Amino Acids and Hyper-LDL-Cholesterolemia: A Case–Control Study Using Interpretable Machine-Learning Models in Chinese Children and Adolescents

<b>Background</b>: Plasma branched-chain amino acid (BCAA) concentrations are positively associated with low-density lipoprotein cholesterol (LDL-C) levels. However, the relationship between dietary branched-chain amino acids and hyper-LDL-cholesterolemia is unclear in children and adolescents. <b>Methods</b>: This study explored the correlation between BCAAs and hyper-LDL-cholesterolemia risk through propensity score matching and conditional logistic regression. Machine learning based on LightGBM indicated the important role of BCAAs in the prediction of hyper-LDL-cholesterolemia. To examine the dose-response relationship, Restricted Cubic Splines (RCS) and receiver operating characteristic curves (ROC) were employed. The causal link between BCAA and cardiovascular disease (CVD) was explored via mediation Mendelian randomization. <b>Results</b>: For every 1 g/day increment in the intake of isoleucine, leucine, and valine, there was a corresponding 30%, 11%, and 16% rise in the risk of hyper-LDL-cholesterolemia, respectively. The optimal cut-off values stood at 5.53, 6.40, and 4.18 g/day, respectively. Utilizing the inverse variance weighted method for estimation revealed that the total effect of BCAA on CVD was OR = 1.06 (95% CI: 1.02~1.11), with <i>p</i> = 0.005. The indirect effect, mediated by LDL-C, was OR = 1.02 (95% CI: 1.00~1.02), with <i>p</i> = 0.026. The direct effect was noted at OR = 1.05 (95% CI: 1.01~1.09), with <i>p</i> = 0.017. <b>Conclusions</b>: Dietary BCAAs are positively correlated with hyper-LDL-cholesterolemia in children and adolescents. LDL-C serve as a mediator of CVD caused by BCAAs.