Metabolic and Immunomodulatory Effects of α-Ketoglutarate in Burn Injuries: A Systematic Review

Severe burns unleash a hyper-catabolic and immunosuppressive state that erodes lean tissue and delays repair. Alpha-ketoglutarate (α-KG), usually delivered enterally as the dipeptide ornithine α-ketoglutarate, feeds the tricarboxylic-acid cycle, donates nitrogen for amino-acid synthesis, and modulates collagen formation and immunity. We systematically appraised the biological mechanisms, delivery strategies, and clinical outcomes associated with α-KG/OKG in burn care to clarify its therapeutic value and translational readiness. A PRISMA-2020-compliant search of PubMed, EMBASE, Web of Science, Cochrane, and Google Scholar up to May 2025 identified clinical, in-vivo, and relevant in-vitro studies linking α-KG or OKG with thermal injury. Study quality was assessed using the Newcastle-Ottawa Scale, SYRCLE Risk-of-Bias tool, and Oxford Levels of Evidence. Fifteen studies published between 1984 and 2024 met inclusion criteria, including clinical, animal, and mechanistic work, most conducted in France. Across studies, OKG supplementation replenished glutamine and arginine pools, improved nitrogen balance, preserved muscle mass, and promoted wound healing through enhanced collagen synthesis and immune modulation. Clinical data confirmed improved nitrogen retention, reduced muscle breakdown, and faster wound closure. Preclinical studies further showed that α-KG preconditioning enhances stem cell-driven regeneration and vascularization. Additional effects, such as improved glucose tolerance and hepatic enzyme preservation, suggest some benefits occur independently of glutamine pathways. This review highlights α-KG and OKG as promising adjuncts to enhance metabolic recovery, wound repair, and immune competence after burns. Evidence supports improved nitrogen balance and healing, but findings remain limited by heterogeneity and small cohorts, warranting renewed and well-powered studies.