MF. Lu, XY. Qi, JW. Cheng, MY. Wang, SY. Liu, Y. Zhang, XJ. Jiang, Y. Yun, QY. Su, PF. He, SX. Zhang, et al. (2026). The application of low-carbohydrate diet in autoimmune diseases: Mechanisms, evidence, and prospects for clinical translation. Autoimmunity reviews, 25(6), 104071. https://doi.org/10.1016/j.autrev.2026.104071

PubMed 42061668

[Abstract]
Emerging evidence suggests that low-carbohydrate diet (LCD) may exert beneficial effects across multiple autoimmune diseases (AIDs), yet their underlying mechanisms remain insufficiently elucidated and clinical evidence is still limited. This review provides a comprehensive synthesis of mechanistic insights, current clinical findings, and translational perspectives on LCD interventions in AIDs. Mechanistically, LCDs reprogram energy metabolism by shifting immune cell bioenergetics from glycolysis toward fatty acid oxidation and ketone utilization, thereby modulating inflammatory pathways such as NF-κB and the NLRP3 inflammasome. LCDs also reshape the gut microbiota and its metabolites, influencing intestinal barrier integrity and systemic immune responses, while epigenetic regulation-including histone deacetylase inhibition and DNA methylation-further stabilizes regulatory T cell identity and restrains pro-inflammatory gene expression. Clinically, encouraging outcomes have been observed in type 1 diabetes, psoriasis, and multiple sclerosis, whereas evidence in systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease remains scarce and heterogeneous. Importantly, existing data indicate that the optimal dietary pattern may differ across disease contexts, and LCDs are not uniformly superior to alternative dietary strategies. Current challenges include risks of nutrient deficiencies, uncertainties regarding long-term safety, variability in individual responses, and the lack of adequately powered randomized controlled trials. Moving forward, integrative research combining multi-omics, precision nutrition, and disease-specific dietary frameworks is needed to delineate responders, clarify mechanisms, and establish standardized protocols. Collectively, this review provides a structured framework for understanding the mechanistic basis and clinical potential of LCDs in AIDs, and outlines future directions for their safe and effective clinical translation.