Studies have suggested that a ketogenic diet –a high-fat, low-carbohydrate regimen that shifts metabolism from glucose to ketones –may be beneficial for treating depression. However, the evidence comes from case reports and single-arm trials rather than well-controlled randomized clinical trials. To test whether a ketogenic diet can improve depression and associated symptoms, a single-blind randomized clinical trial was conducted with 88 participants with treatment-resistant depression.

Participants were randomized into either a ketogenic diet group or a phytochemical diet group (control). Over the 6 weeks of the study, depression severity, measured by PHQ-9 scores, decreased in both groups. At 6 weeks, improvement in depression symptoms was slightly greater in the ketogenic group, though the difference was not statistically significant. Participants with severe depression had a greater response to the ketogenic diet than participants with moderate depression. The ketogenic diet did not confer statistically significant improvements in anxiety, anhedonia, cognitive impairment, quality of life, or the ability to perform daily activities. Six weeks after study support ended, 48% of participants in the ketogenic group had fully discontinued the diet, and only 20% reported following the diet at least half the days.

This study suggests that a ketogenic diet may have minor antidepressant benefits in treatment-resistant depression, with greater benefit for those with severe depression. In addition, adherence to a ketogenic diet may prove challenging, with few participants continuing after study support ended. Overall, this randomized clinical trial provides evidence that a ketogenic diet may have modest benefits for people with severe treatment-resistant depression and highlights the importance of external support for adherence to a ketogenic diet.

Reference: Gao M et al. JAMA Psychiatry 2026. Epub ahead of print. Abstract