The Ketogenic Diet in Depression: Potential Biological Mechanisms and Current Clinical Evidence - A Narrative Review

Abstract

Background: Depression is a multifactorial psychiatric disorder whose underlying mechanisms extend beyond classical neurotransmitter abnormalities and involve metabolic, inflammatory and neurobiological disturbances. Recent evidence suggests that the pathophysiology of depression involves neuroinflammation, mitochondrial dysfunction, oxidative stress, neurotransmitter dysregulation and alterations in the gut–brain axis. These findings have contributed to growing interest in the field of metabolic psychiatry. Aim: The aim of this review was to summarize the current evidence regarding the potential effects of the ketogenic diet on depressive symptoms and to discuss the biological mechanisms that may underlie these effects. Material and methods: A literature was conducted using PubMed and Google Scholar. The review was based primarily on systematic reviews, meta-analyses, clinical trials, case reports and experimental studies addressing depression, ketogenic diet and metabolic psychiatry. Results: The available evidence suggests that the ketogenic diet may contribute to the alleviation of depressive symptoms through the reduction of neuroinflammation and oxidative stress, improvement of mitochondrial function, modulation of neurotransmitter systems and regulation of the gut–brain axis. Preliminary clinical studies have reported improvements in depressive symptoms among patients following ketogenic interventions. However, the available studies are limited by small sample sizes and short follow-up periods. Conclusions: The ketogenic diet may represent a promising adjunctive intervention for the management of depressive symptoms. Nevertheless, the current evidence remains insufficient to recommend it as a standard treatment for depression. Further large-scale, long-term randomized controlled trials are required to establish its efficacy and safety in patients with depressive disorders.