Summary:
This study is a systematic review and meta-analysis that examined the association between the ketogenic diet and mental health outcomes in adults, with particular focus on depression and anxiety symptoms. The ketogenic diet, which is very low in carbohydrates, has been proposed to influence mental health through biological mechanisms such as changes in inflammation, neurotransmitter activity, and mitochondrial function. Across 50 included studies involving more than 41,000 participants, this study found that ketogenic diets were associated with modest improvements in depressive symptoms in randomized controlled trials. The association appeared stronger in studies that confirmed ketosis biochemically, used stricter carbohydrate restriction, included non-obese participants, or compared ketogenic diets with non-high-carbohydrate control diets. In contrast, randomized trials did not demonstrate a significant association between ketogenic diets and anxiety symptoms. Overall, this study suggests that ketogenic diets may be linked with reductions in depressive symptoms, but the evidence for anxiety remains unclear. The authors highlight that differences between study methods, variations in dietary protocols, and relatively short follow-up periods limit firm conclusions. They conclude that larger, well-designed randomized controlled trials with standardized ketogenic protocols and longer monitoring are required to clarify effectiveness.
Abstract:
Importance Ketogenic diets (KDs) have been hypothesized to influence mental health through pathways involving mitochondrial function, inflammation, and neurotransmitters, but their therapeutic value in psychiatric populations remains uncertain. Objective To assess the associations between KDs and mental health outcomes in adults, with a focus on depressive and anxiety symptoms. Data Sources MEDLINE, Embase, and APA PsycINFO were searched on April 18, 2025. Additional studies were identified through manual searches and clinical trial registries. Study Selection Studies involving adults aged 18 years or older receiving a KD (<26% energy from carbohydrates or <50 g/day) and assessed with validated psychiatric scales were eligible. Designs included randomized clinical trials (RCTs), quasi-experimental (QSE) studies, cross-sectional studies, case series, and case reports. Data Extraction and Synthesis Data were extracted by 1 reviewer and verified by 2 others. Risk of bias was assessed using critical appraisal tools from the Joanna Briggs Institute. Random-effects meta-analyses were run separately for RCTs and QSEs. Main Outcomes and Measures The primary outcome was changes in psychiatric symptom severity measured by standardized scales, reported as standardized mean differences (SMDs) or standardized mean change using change scores (SMCCs). Results A total of 50 studies (41 718 participants) were included. Ten RCTs on KD for depressive symptoms vs control diets showed a significant association (SMD, −0.48; 95% CI, −0.87 to −0.10; I2 = 67.2%), with stronger associations in studies using ketone monitoring, nonobese participants, very low-carbohydrate interventions, and non–high-carbohydrate comparators. Nine RCTs on anxiety showed no significant association (SMD, −0.03; 95% CI, −0.18 to 0.12; I2 = 41%). In QSEs, 9 on depressive symptoms showed a consistent association (SMCC, −0.66; 95% CI, −0.83 to −0.50; I2 = 0%), and 6 on anxiety showed similar results (SMCC, −0.58; 95% CI, −0.81 to −0.36; I2 = 0%). Conclusions and Relevance In this systematic review and meta-analysis, KDs were associated with modest improvements in depressive symptoms, particularly with biochemical ketosis verification, while anxiety evidence was inconclusive. Given heterogeneity, comparators, and short follow-up, well-powered trials with standardized, verified protocols, structured support, and prespecified outcomes are needed to confirm efficacy and durability.
Article Publication Date: 05/11/2025
DOI: 10.1001/jamapsychiatry.2025.3261
