Effect of branched-chain amino acid on depression: a systematic review

BACKGROUND: Depression is a global mental health disorder and is linked to impaired quality of life and increased risk of chronic diseases. Emerging evidence suggests that branched-chain amino acids (BCAAs), including valine, isoleucine and leucine, may influence neurobiological pathways involved in depression through modulation of neurotransmitter signaling. METHODS: A systematic literature search was conducted across multiple databases from their inception to April 2026. Studies evaluating BCAA supplementation or dietary intake in relation to depression were included. Cross-sectional studies, observational studies, retrospective studies, randomized controlled trials and case-control studies available in English were considered. Data extraction and quality assessment were conducted using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. RESULTS: Eleven studies involving 3902 participants were included. Seven studies reported a reduction in depressive symptoms following BCAA supplementation or higher dietary intake. Improvement was observed among elderly populations and patients with metabolic or chronic conditions. Observational studies demonstrated an inverse association between dietary BCAA intake and depression-related outcomes. However, several studies reported non-significant findings and heterogeneity existed regarding study design, participant characteristics, dosage and assessment methods. Evidence also suggested that combined exercise and BCAA interventions provide additional benefits. CONCLUSION: Current evidence suggests that BCAAs may play a potential role in depression and mental health outcomes. Findings from intervention, dietary exposure and biomarker studies indicate a possible association between BCAAs and depressive symptoms; however, the available evidence remains heterogeneous and inconclusive. Further well-designed, adequately powered clinical trials are required to establish the therapeutic role of BCAAs in depression.