DIME Trial: New study finds a ketogenic diet may help some with severe depression

Mar 16, 2026

Dr. Megan Kirk Chang, a senior metabolic psychiatry researcher at Oxford with a PhD in kinesiology, co-led the DIME randomized trial testing a ketogenic versus plant-rich diet for treatment-resistant depression. She discusses trial design, why the modest keto signal matters, adherence and cravings, ketone monitoring choices, and plans for larger follow-up studies.

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INSIGHT

Six Week Pilot Shows Signal Not Definitive Proof

A six-week pilot randomized trial tested a tightly controlled ketogenic diet versus a plant-rich ‘phyto’ diet for treatment-resistant depression.
Both arms had clinically meaningful PHQ-9 reductions, with a modest non-significant advantage for the ketogenic arm.

INSIGHT

Modest Ketogenic Signal But Poor PostTrial Retention

Even without meeting the pre-specified between-group threshold, the ketogenic arm showed a modest favorable signal and many participants benefited.
Drop-off from the ketogenic diet was high after protocol end, motivating design changes for retention.

INSIGHT

Active Control Was Easy Plant Rich Diet With Coaching

The control arm was an active phytonutrient-focused diet, not a no-treatment control, and received matched dietetic support.
The phyto protocol emphasized a rotating color wheel of fruits and vegetables and was intentionally easy to implement.

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Can the ketogenic diet help improve symptoms for individuals living with treatment-resistant depression?

In this conversation, Dr. Bret Scher sits down with Dr. Megan Kirk Chang, a senior researcher in metabolic psychiatry at the University of Oxford and a co-author of the recently published DIME trial.

This study represents the first randomized clinical trial to evaluate a ketogenic diet in adults with treatment-resistant depression.

Participants were assigned to either a ketogenic diet or a plant-rich comparison diet for six weeks to assess whether dietary intervention could influence depressive symptoms. Both groups experienced meaningful improvements in depression scores, with the ketogenic diet slightly outperforming the control group at 6 weeks.

While the difference between groups did not reach the threshold for statistical significance, the findings suggest a positive signal that warrants further investigation.

In this interview, Dr. Kirk Chang reflects on:

The strengths of the study and where she sees opportunity for improvement.
What the modest difference between diets might mean
Why early pilot trials are designed to detect signals rather than definitive answers
What the study revealed about adherence, cravings, and behavioral factors
How these results will inform larger and longer clinical trials now being planned

As Dr. Kirk Chang explains, this six-week pilot trial was designed as proof-of-concept research to determine whether there is enough signal to justify larger studies in metabolic psychiatry.

At Metabolic Mind, we view studies like this as an important step in a growing scientific effort to understand how metabolism and nutrition may influence serious mental illness. Each new study contributes to the evolving evidence base that will help researchers determine who may benefit, why, and under what conditions.

🔗 To learn more about the available evidence for ketogenic therapy in depression and our top resources, visit our Depression Topic Page: https://www.metabolicmind.org/resources/topics/keto-for-depression/

🔎 Have questions about how to apply metabolic therapies effectively? Submit them at metabolicmind.org/questions to be featured in a future Metabolic Mailbag episode.

Expert Featured:

Dr. Megan Kirk Chang, PhD

Senior Researcher, Department of Psychiatry, University of Oxford
https://x.com/DrMegKirkChang
https://www.linkedin.com/in/megankirkchang/

Resources Mentioned:

A Ketogenic Diet for Treatment-Resistant Depression: A Randomized Clinical Trial

https://doi.org/10.1001/jamapsychiatry.2025.4431

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Learn more about metabolic psychiatry and find helpful resources at https://metabolicmind.org/

About us:

Metabolic Mind is a non-profit initiative of Baszucki Group working to transform the study and treatment of mental disorders by exploring the connection between metabolism and brain health. We leverage the science of metabolic psychiatry and personal stories to offer education, community, and hope to people struggling with mental health challenges and those who care for them.

Our channel is for informational purposes only. We are not providing individual or group medical or healthcare advice nor establishing a provider-patient relationship. Many of the interventions we discuss can have dramatic or potentially dangerous effects if done without proper supervision. Consult your healthcare provider before changing your lifestyle or medications.