A clinical trial is set to test whether diet could help reduce depressive symptoms in people with bipolar disorder, comparing a high fat, low carbohydrate diet with standard NHS healthy eating advice.
ENERGISE-BD, led by the Universities of Edinburgh and Birmingham, will recruit some 200 people with the condition to better understand how nutrition might support mental health.
If successful, the findings could point to a new treatment approach for people living with bipolar disorder, experts say.
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 – which may not respond to standard antidepressants, and can have a major impact on quality of life.
The £7.9 million ENERGISE-BD trial, funded by Wellcome and designed in partnership with people with lived experience, follows a smaller study from the University of Edinburgh team, which suggests that following a high fat, low carbohydrate diet – known as a ketogenic diet – could be helpful in people with bipolar disorder. However, it is also possible that the UK's standard healthy eating advice, known as the NHS EatWell Guide, may also help those with bipolar depression, researchers say.
Dietary choices can influence how the brain generates energy. Without carbohydrates to produce glucose – the body’s usual source of energy – the ketogenic diet helps the body to produce chemicals called ketones. Ketones may be a more efficient fuel source for brain tissue than glucose.
Trial participants will be supported by dietitians to follow one of two diets over a 12-week period, alongside their usual medication, and will be monitored for any changes in depressive symptoms – such as differences in mood and energy. Half will follow a keto diet and the remaining volunteers will adhere to the nutritionally balanced EatWell approach.
About half of the study participants will have brain scans to understand how changes in brain chemistry may be connected to improved mood. Alongside clinical outcomes, the study will look at how easy the diets are to follow, as well as any potential cost implications for the NHS.
Experts say the potential of nutritional interventions to help manage a severe mental illness like bipolar disorder is novel and promising, but caution that the research is still in the early stages.
The trial will initially recruit volunteers in the central belt of Scotland before expanding to the Birmingham area in early 2027. People who would like to take part can register their interest on the study website: www.medicine-vet-medicine.ed.ac.uk/energise-bd
Professor Daniel Smith, ENERGISE-BD co-lead from the University of Edinburgh’s Institute for Neuroscience and Cardiovascular Research, said: “This is the world’s first large-scale randomised 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.”
Professor Steven Marwaha, ENERGISE-BD co-lead from the University of Birmingham, said: "We need new treatments for bipolar disorder. 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 eat well plan can treat depressive symptoms in bipolar disorder. We are evaluating this in a methodologically robust trial, including participants from the midlands, a socio-economic 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.”
Tayla McCloud, Senior Research Manager at Wellcome, said: "This innovative research study could pinpoint a new mechanism by which we can treat symptoms of depression in people with bipolar disorder. 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 experience who codesigned the research. Research like this, addressing the symptoms that matter to people with lived experience, could meaningfully improve the lives of people with mental health problems."
The study also involves key academic and delivery partners including the Edinburgh Clinical Trials Unit, NHS Lothian, and Birmingham and Solihull Mental Health NHS Foundation Trust, and is supported by patient organisations including Bipolar Scotland and Bipolar UK.
The study team will include those with lived experience of bipolar depression, as part of a Lived Experience Advisory Panel, to ensure the research is grounded in patient priorities.
Randomized controlled/clinical trial
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