Metabolic and Immunomodulatory Effects of α-Ketoglutarate in Burn Injuries: A Systematic Review
Clinical Snapshot
PICO Framework
| P — Population | Patients with thermal burn injuries (severe burns) |
| I — Intervention | Alpha-ketoglutarate (α-KG) or ornithine α-ketoglutarate (OKG) supplementation |
| C — Comparator | Standard burn care or control treatments |
| O — Outcomes | Nitrogen balance, muscle mass preservation, wound healing, collagen synthesis, immune function, glucose tolerance |
Bottom Line
This systematic review suggests α-ketoglutarate and ornithine α-ketoglutarate supplementation may improve nitrogen balance, preserve muscle mass, and enhance wound healing in burn patients through metabolic and immunomodulatory mechanisms. However, the evidence base remains limited by small studies, methodological heterogeneity, and lack of quantitative synthesis. While the biological rationale is compelling and consistent directional effects are reported across studies, the authors appropriately conclude that well-powered randomised controlled trials are needed before recommending routine clinical use. The intervention appears safe and potentially beneficial as adjunct therapy, but current evidence is insufficient to change standard practice. Australian clinicians should await stronger evidence before considering implementation, particularly given regulatory requirements for therapeutic use.
Key Findings
P Value: Not reported for pooled analysis
Effect Size: Not quantified - qualitative synthesis only
Primary Outcome: Improved nitrogen balance and reduced muscle breakdown
Nnt Or Sensitivity: Not calculated - insufficient data for quantitative synthesis
Confidence Interval: Not provided
Clinical Application
Enteral OKG supplementation appears feasible as adjunct therapy Would require TGA approval for therapeutic use; not currently listed on PBS; aligns with ANZBA burn care guidelines for nutritional support Patients with severe thermal burns requiring nutritional support
Abstract
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 (OKG), 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.
References
- 1.Niederegger, T., Munzinger, R., Schaschinger, T., Brandt, J. C., Knoedler, L., Knoedler, S., Palackic, A., Panayi, A. C., & Hundeshagen, G. (2026). Metabolic and immunomodulatory effects of α-ketoglutarate in burn injuries: A systematic review. Journal of Burn Care & Research, Article irag002. https://doi.org/10.1093/jbcr/irag002
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