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Ketogenic diets and depression and anxiety: a systematic review and meta-analysis
Ketogenic diets (KDs) have been proposed to influence mental health through mechanisms involving mitochondrial function, inflammation, and neurotransmitter pathways. However, their therapeutic efficacy in psychiatric populations remains ambiguous. This systematic review aims to evaluate the associations between KDs and mental health outcomes in adults, concentrating on depressive and anxiety symptoms. Data were sourced from MEDLINE, Embase, and APA PsycINFO, with searches conducted on April 18, 2025. Additional studies were identified through manual searches and clinical trial registries. Eligible studies included adults aged 18 years or older who adhered to a KD (defined as <26% of energy from carbohydrates or <50 g/day) and were assessed using validated psychiatric scales. The review encompassed randomized clinical trials (RCTs), quasi-experimental (QSE) studies, cross-sectional studies, case series, and case reports. Data extraction was performed by one reviewer and verified by two others, with risk of bias assessed using critical appraisal tools from the Joanna Briggs Institute. Random-effects meta-analyses were conducted separately for RCTs and QSEs. The primary outcome was change in psychiatric symptom severity, reported as standardized mean differences (SMDs) or standardized mean change scores (SMCCs). A total of 50 studies involving 41,718 participants were included. Ten RCTs assessing the impact of KDs on depressive symptoms versus control diets revealed a significant association, with stronger effects noted in studies that monitored ketone levels, included nonobese participants, utilized very low-carbohydrate interventions, and employed non-high-carbohydrate comparators. Conversely, nine RCTs focused on anxiety did not show a significant association. In QSEs, nine studies on depressive symptoms demonstrated a consistent association, while six studies on anxiety yielded similar results. In conclusion, this systematic review and meta-analysis indicate that KDs are associated with modest improvements in depressive symptoms, particularly when biochemical ketosis is verified, while the evidence regarding anxiety remains inconclusive. Due to the observed heterogeneity, varying comparators, and short follow-up durations, further well-powered trials with standardized protocols, structured support, and prespecified outcomes are necessary to confirm the efficacy and durability of these findings. [NPID: Ketogenic diet, depression, anxiety, systematic review]
Year: 2025
