Ketogenic metabolic therapy: low-carbohydrate interventions as novel neuroprotective strategies for cognitive dysfunction in diabetes

Cognitive dysfunction is an increasingly recognized complication of diabetes, contributing substantially to morbidity in the aging population, yet disease-modifying therapies remain scarce. Dietary intervention, a cornerstone of diabetes management, may offer neuroprotective potential. Low-carbohydrate ketogenic diets (LCKDs), typically restricting carbohydrates to < 50 g/day, effectively improve glycemic control and metabolic health. Emerging preclinical and clinical evidence suggests that LCKDs may also confer cognitive benefits through mechanisms including enhanced mitochondrial bioenergetics, reduced neuro-inflammation, and modulation of the gut-brain axis. This narrative review critically evaluates the current evidence regarding the efficacy, mechanisms, and safety of LCKDs for managing diabetes-associated cognitive dysfunction, identifies key limitations in the existing literature, and proposes a framework for future research to enhance translational value.