A KETOGENIC diet may offer modest antidepressant benefits for people with treatment-resistant depression, according to a UK randomised clinical trial showing greater symptom improvement compared with a controlled diet after six weeks.
Why the Ketogenic Diet Is Being Tested in Depression
Interest in the ketogenic diet has grown beyond epilepsy and metabolic disease, with emerging evidence suggesting potential effects on brain energy metabolism, inflammation, and neurotransmission. Case reports and small observational studies have hinted at antidepressant effects, but robust randomised data have been limited. Dietary interventions, if effective, could provide a low-cost adjunctive strategy alongside medication and psychological support for patients with depresssion. The current trial was designed to test whether a ketogenic diet could meaningfully improve depressive symptoms when compared with a well-matched control diet offering similar professional support.
Trial Design and Depression Outcomes on a Ketogenic Diet
The randomised clinical trial enrolled 88 adults across the UK with treatment-resistant depression, defined by a PHQ-9 score of 15 or higher. Participants were assigned 1:1 to either a ketogenic diet providing less than 30 g of carbohydrates per day or a phytochemical control diet encouraging increased fruit and vegetable intake and healthier fats. Both groups received equal dietetic support over six weeks. Depression severity fell substantially in both groups. The mean PHQ-9 score change at week 6 was −10.5 (7.0) in the ketogenic diet group and −8.3 (5.1) in the control group. The between-group difference at six weeks was −2.18 (95% CI, −4.33 to −0.03; P = .05; Cohen d, −0.68). At 12 weeks, the difference narrowed and was no longer statistically significant. No serious adverse events were reported.
Clinical Implications and Future Directions
The findings suggest that a ketogenic diet may offer small short-term antidepressant benefits for some individuals with treatment-resistant depression, particularly those with more severe symptoms. However, adherence proved challenging, with only 9% continuing the diet once intensive support ended. There were no clear benefits for anxiety, cognition, or functional outcomes. Clinically, the results support cautious exploration of ketogenic diets as an adjunct rather than a standalone treatment. Further research is needed to identify which patients may benefit most and to develop more sustainable dietary approaches suitable for long-term clinical use.
Reference
Gao M et al. A ketogenic diet for treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2026;DOI:10.1001/jamapsychiatry.2025.4431.
