Ketogenic Diets May Reduce Depressive Symptoms
Ketogenic diets (KDs) were associated with modest improvements in depressive symptoms in a recent systematic review and meta-analysis. Researchers published their findings in JAMA Psychiatry.
“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,” wrote Reinhard Janssen-Aguilar, MD, Interventional Psychiatry Program, St Michael’s Hospital, Toronto, Ontario, Canada, and study coauthors.
The researchers extracted data from 50 total studies, which included randomized clinical trials (RCTs), quasi-experimental (QSE) studies, cross-sectional studies, case series, and case reports. Studies involved 41,718 total participants who were aged 18 years or older, consumed a KD, defined as receiving <26% energy from carbohydrates or <50 g/day, and were assessed with valid psychiatric scales. Depressive and anxiety symptoms were the most frequently assessed outcomes.
READ>>Serial Ketamine Infusions Fail to Show Benefit as Adjunctive Therapy for MDD
In their analysis, researchers reported that in 10 of the included RCTs, KDs were associated with significant reductions in depressive symptoms compared to control diets (standardized mean difference [SMD], −0.48; 95% CI, −0.87 to −0.10; I2 = 67.2%). This was particularly true in studies with ketone monitoring, nonobese participants, very low-carbohydrate interventions, and non–high-carbohydrate comparators.
Of the quasi-experimental studies, the 9 that evaluated depressive symptoms also associated KDs with improvement in depressive symptoms (pooled standardized mean change using change scores [SMCC], −0.66; 95% CI, −0.83 to −0.50; I2 = 0%).
Findings on anxiety were less conclusive; while RCT data did not establish an association between anxiety and KDs (SMD, −0.03; 95% CI, −0.18 to 0.12; I2 = 41%), 6 QSEs indicated that KDs moderately improved anxiety symptoms (SMCC, −0.58; 95% CI, −0.81 to −0.36; I2 = 0%).
“Our findings in this systematic review and meta-analysis suggest that KDs may confer therapeutic benefits for depressive symptoms, whereas evidence for anxiety remains preliminary,” the authors wrote. “Discrepancies between RCTs and QSEs likely reflect design differences and intervention fidelity.”
The researchers emphasized that their findings were strengthened by the analysis’ large, pooled sample size and inclusion of diverse psychiatric diagnoses and dietary protocols. However, their heterogenous clinical population may also have introduced variability not fully addressed in their analysis.
“Future work should prioritize large, preregistered RCTs with standardized KD protocols, rigorous ketone monitoring, appropriate comparators, structured dietary support, extended follow-up, and predefined psychiatric outcomes to determine who benefits and under what conditions,” the researchers concluded.