<p>Maple syrup urine disease (MSUD) is a genetic disorder of the metabolism of branched-chain amino acids (BCAAs). We investigate the effects of treatment with dietary restriction and carnitine supplementation in MSUD patients. During treatment, patients were placed on a restricted diet and received a semi-synthetic formula enriched with carnitine. Our results revealed that treated patients showed elevated levels of neurodegeneration biomarkers (BDNF and PDGF-BB), while levels of TBARS and isoprostanes, indicators of lipid oxidative damage, were significantly decreased compared to diagnostic group. We observed an increase in L-carnitine levels after treatment, which suggests a positive response to supplementation. BCAAs and branched-chain α-keto acid dehydrogenase levels were elevated at diagnosis but decreased after treatment, indicating therapeutic efficacy. Our results highlight the importance of carnitine supplementation in the treatment of MSUD patients, possibly mitigating the neurological and metabolic involvement of the disease, providing valuable insights to optimize therapy and improve clinical outcomes.</p> Graphical abstract <p></p>