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

Abstract

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.

Keywords: LCKDs; cognitive dysfunction; diabetes mellitus; gut-brain axis; low-carbohydrate ketogenic diet; mild cognitive impairment; nutritional ketosis.