SCOTLAND — The Universities of Edinburgh and Birmingham have launched the £7.9 million ENERGISE-BD trial to determine if a ketogenic diet reduces depressive symptoms in people with bipolar disorder compared to standard NHS dietary advice. The study aims to evaluate whether nutritional interventions can serve as a viable treatment for bipolar depression, a condition that often does not respond to standard antidepressants. The possibility that diet could be a treatment for bipolar disorder is being investigated in this new trial.

Professor Daniel Smith described the initiative as the world's first large-scale randomized controlled trial of nutrition as a potential new treatment for bipolar depression. "The possibility that diet could be a treatment for bipolar disorder is novel and potentially groundbreaking," Smith said. "This is the world's first large-scale randomized controlled trial of nutrition as a potential new treatment for bipolar depression," he said.

The trial will recruit approximately 200 people with bipolar disorder to participate in the study. Half of the participants will follow a ketogenic diet, while the other half will adhere to the NHS EatWell approach, which serves as the UK's standard healthy eating advice. Trial participants will be supported by dietitians to follow one of the two diets over a 12-week period alongside their usual medication.

"ENERGISE-BD will discover whether a ketogenic diet or the NHS eat well plan can treat depressive symptoms in bipolar disorder," he said. The study design involves a high fat, low carbohydrate diet for the intervention group to test its efficacy against the control group receiving standard guidance.

Bipolar disorder is characterized by episodes of depression and mania. Most people with the condition are symptomatic between episodes, often experiencing long-term depressive symptoms known as bipolar depression. Because these symptoms may not respond to standard antidepressants, researchers emphasize the need for alternative approaches. "We need new treatments for bipolar disorder," he said.

The mechanism behind the ketogenic diet involves the body producing chemicals called ketones when carbohydrates are restricted. Without carbohydrates to produce glucose, the body shifts to burning fats, and these ketones may serve as a more efficient fuel source for brain tissue than glucose. About half of the study participants will undergo brain scans to understand how changes in brain chemistry may be connected to improved mood.

Tayla McCloud, Senior Research Manager, noted that the research addresses symptoms that matter to patients. "This innovative research study could pinpoint a new mechanism by which we can treat symptoms of depression in people with bipolar disorder," McCloud said. She added that the intervention was inspired by reports from individuals who found symptom improvement while trying the keto diet. "Research like this, addressing the symptoms that matter to people with lived experience, could meaningfully improve the lives of people with mental health problems," she said.

Smith emphasized the importance of including a diverse population in the trial. "People with lived experience of the condition often prioritize research into non-pharmacological treatments," he said. The study aims to include participants from the midlands, a socio-economic and ethnically diverse area. "We are evaluating this in a methodologically robust trial, including participants from the midlands, a socio-economic and ethnically diverse area," he said.

"We want to understand if it could be effective in a sample which represents the full range of characteristics of people with bipolar disorder," Smith added. The trial will initially recruit volunteers in the central belt of Scotland before expanding to the Birmingham area in early 2027. The study involves academic and delivery partners including the Edinburgh Clinical Trials Unit, NHS Lothian, and Birmingham and Solihull Mental Health NHS Foundation Trust.

In parallel developments, a UC San Francisco pilot study suggests that reducing ultra-processed food intake may help improve depression symptoms. That study, published in JAMA Psychiatry on September 23, 2026, involved 20 people with depression. Participants in the UC San Francisco study reduced ultra-processed food intake by more than 85% and experienced moderate to large improvements across three measures of depression. Anxiety scores also improved modestly for participants in that study.

The UC San Francisco study was funded by the National Institutes of Health. All participants in that study had a high body mass index and at least one metabolic disorder such as hypertension, diabetes, or high cholesterol. Seventy percent of participants were female, and the average age was 44.

Fourteen participants had anxiety. Participants were divided into two groups, with one group following their usual diet for four weeks and the other switching to a low ultra-processed food diet. After four weeks, the groups switched diets. Participants selected and bought their own food with guidance from the research team. UC San Francisco plans to enroll participants in a larger follow-up study on ultra-processed foods and depression in 2028.

Why It Matters

The trial's scope includes assessing the economic impact and feasibility of dietary interventions within the NHS, which could influence future healthcare resource allocation. With a budget of £7.9 million and a timeline extending to 2031, the study aims to provide robust evidence on whether nutritional ketosis can offer a new mechanism for treating depression. The concurrent interest in dietary impacts on mental health, seen in studies on ultra-processed foods, points to a broader scientific inquiry into the connection between diet and brain chemistry.

Timeline

The ENERGISE-BD trial is registered on the University of Edinburgh Research Explorer with a status of 'Active' and a planned duration from February 1, 2026, to March 31, 2031. The UC San Francisco study was published in JAMA Psychiatry on September 23, 2026. The ENERGISE-BD trial will initially recruit volunteers in the central belt of Scotland before expanding to the Birmingham area in early 2027.

What's New

Participants in the UC San Francisco study reduced ultra-processed food intake by more than 85%. A previous pilot study of the ketogenic diet for bipolar disorder obtained ethical approval from the South East Scotland Research Ethics Committee (approval number: 22/SS/0007) and was approved by NHS Lothian Research and Development.

The ENERGISE-BD trial received £7.9 million in funding from the Wellcome Trust. The ENERGISE-BD trial will assess healthcare resource use and associated costs of the ketogenic diet intervention, as part of its evaluation of feasibility and economic impact.