UK trial to test ketogenic and healthy-eating diets for bipolar depression

A £7.9 million randomized clinical trial will test whether a high-fat, low-carbohydrate ketogenic diet or standard NHS healthy-eating advice can reduce depressive symptoms in people with bipolar disorder. The ENERGISE-BD study, led by the Universities of Edinburgh and Birmingham, plans to recruit about 200 participants with the condition and compare the two diets over 12 weeks alongside participants’ usual medication. The protocol is intended to assess diet as a potential addition to established care; it has not yet produced evidence of clinical benefit.

Researchers will randomly allocate half of the participants to the ketogenic diet and the other half to the nutritionally balanced approach set out in the NHS EatWell Guide. Dietitians will support participants in following their assigned plan, while investigators monitor changes in depressive symptoms, including differences in mood and energy. The study will also examine how easy each diet is to follow and assess potential cost implications for the National Health Service. It will initially recruit in Scotland’s central belt before expanding to the Birmingham area in early 2027.

ENERGISE-BD follows a smaller University of Edinburgh study that suggested a ketogenic diet could be helpful for some people with bipolar disorder. The larger trial was funded by Wellcome and designed in partnership with people who have lived experience of bipolar depression. A Lived Experience Advisory Panel will remain involved in the research so that the study reflects patient priorities. Delivery and academic partners include the Edinburgh Clinical Trials Unit, NHS Lothian, and Birmingham and Solihull Mental Health NHS Foundation Trust, while Bipolar Scotland and Bipolar UK are among the supporting patient organisations.

About half of the participants will undergo brain scans intended to help researchers examine whether changes in brain chemistry are connected with any improvement in mood. The trial is testing both clinical outcomes and possible biological mechanisms associated with the two dietary approaches. A ketogenic diet restricts carbohydrates, which are the body’s usual source of glucose for energy. In the absence of carbohydrates, the body produces chemicals called ketones, which may be a more efficient fuel source for brain tissue. Whether this metabolic process affects depressive symptoms, and whether any observed changes are associated with brain-chemistry differences, remains an open question for the planned trial.

Daniel Smith, ENERGISE-BD co-lead from the University of Edinburgh’s Institute for Neuroscience and Cardiovascular Research, described the project as the world’s first large-scale randomized controlled trial of nutrition as a potential new treatment for bipolar depression. Steven Marwaha, co-lead from the University of Birmingham, said the study will evaluate whether a ketogenic diet or the NHS Eatwell plan can treat depressive symptoms in bipolar disorder. He said the trial would include a socioeconomically and ethnically diverse sample from the Midlands, intended to represent a wider range of people with the condition. The researchers characterized nutritional interventions for severe mental illness as novel and promising but cautioned that the research remains at an early stage.

Subject of Research: A randomized trial of ketogenic and NHS healthy-eating diets for depressive symptoms in bipolar disorder

Article Title: Innovative UK trial to explore impact of diet on bipolar depression

Article References: Innovative UK trial to explore impact of diet on bipolar depression. Original publication (Bibliographic details unavailable.)

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Keywords: bipolar depression, ketogenic diet, randomized trial, clinical nutrition, depressive symptoms, brain metabolism, brain scans, mental health, Wellcome, NHS, Innovative, trial