A clinical trial will assess whether switching to a high-fat, low-carbohydrate diet could help to reduce depressive symptoms in people with bipolar disorder.

The trial is led by the Universities of Edinburgh and Birmingham, and will recruit 200 people with the condition to better understand how nutrition might support mental health. If a link is established, this could lead to a new treatment approach for people living with bipolar disorder, experts have said.

“This is the world’s first large-scale randomised controlled trial of nutrition as a potential new treatment for bipolar depression,” said Daniel Smith, professor of psychiatry with a special interest in bipolar disorder, honorary consultant psychiatrist at NHS Lothian, and trial co-lead from the University of Edinburgh’s Institute for Neuroscience and Cardiovascular Research. “The possibility that diet could be a treatment for bipolar disorder is novel and potentially groundbreaking.” 

Bipolar disorder is characterised by episodes of depression and mania, but most people with the condition are also symptomatic between episodes. This often involves long-term depressive symptoms, known as bipolar depression. This type of depression may not respond to standard antidepressants, and it can have a major impact on quality of life.

Funded by Wellcome and designed in partnership with people with lived experience of bipolar depression, the £7.9 million ENERGISE-BD trial follows a smaller study carried out by the University of Edinburgh team, which suggested that following a high-fat, low-carbohydrate (ketogenic) diet could be helpful in people with bipolar disorder. But it is also possible that the NHS EatWell Guide may help those with this type of depression, and that is something the trial will also look at.

New treatments

“We need new treatments for bipolar disorder,” said Steven Marwaha, professor of psychiatry, NHS consultant psychiatrist working in Birmingham and Solihull, and trial co-lead. “People with lived experience of the condition often prioritise research into non-pharmacological treatments. ENERGISE-BD will discover whether a ketogenic diet or the NHS EatWell approach can treat depressive symptoms in bipolar disorder. We are evaluating this in a methodologically robust trial, including participants from the Midlands, a socio-economically and ethnically diverse area. We want to understand if it could be effective in a sample which represents the full range of characteristics of people with bipolar disorder.”

Trial participants will be supported by dietitians to follow one of two diets over a 12-week period, alongside their usual medication. They will be monitored for any changes in depressive symptoms such as differences in mood and energy. Around half of the trial participants will have brain scans to understand how changes in brain chemistry may be connected to improved mood. Clinical outcomes will be reviewed, and the trial will also look at how easy the diets are to follow and any potential cost implications for the NHS.

The trial will initially recruit volunteers in the central belt of Scotland, before expanding to the Birmingham area in early 2027. 

“This innovative research study could pinpoint a new mechanism by which we can treat symptoms of depression in people with bipolar disorder,” added Tayla McCloud, senior research manager at Wellcome. “Crucially, this intervention was inspired by reports from people with lived experience who had found an improvement in their symptoms when trying the keto diet, and the core study team includes people with lived experiences who co-designed the trial. 

“Research like this, addressing the symptoms that matter to people with lived experience, could meaningfully improve the lives of people with mental health problems.”