University of Edinburgh research is exploring how the body’s energy systems intersect with severe mental illness. From lived experience to large-scale clinical trials, the emerging field of metabolic psychiatry is opening new avenues for understanding and treatment. 

On a routine bus journey, Dr Iain Campbell became aware of an unfamiliar sense of calm. Where his thoughts had long felt clouded, he experienced a clarity that had been absent for years. 

Iain had been living with bipolar disorder with symptoms that included depression and severe fatigue. At the same time, he had started making dietary changes for his general health, cutting back on carbohydrates in favour of proteins and fats. In doing so, he inadvertently entered ketosis – a metabolic state in which the body uses ketones rather than glucose as its primary fuel. That’s when he noticed a positive difference in the symptoms of his bipolar disorder. 

Curious about the changes, Iain began tracking his ketone levels alongside his mood. Over time, a pattern emerged. Higher ketone levels aligned with improvements in mood and mental clarity.

Dr Iain Campbell

What began as a personal observation then evolved into a research question.  

Iain reported his experiences of a ketogenic diet to Professor Daniel Smith, Chair of Psychiatry at Edinburgh, who recognised the scientific potential of examining metabolism alongside psychiatric care. Rather than viewing dietary intervention as peripheral, Professor Smith saw an opportunity to explore the biological links between mental and physical health within a rigorous clinical framework. With early philanthropic support enabling a pilot study, this collaboration helped establish metabolic psychiatry as a growing focus within Edinburgh’s research landscape. 

A whole-body perspective

Conditions such as bipolar disorder, schizophrenia and severe depression are increasingly understood not only as disorders of the brain, but as illnesses that interact with the body’s metabolic systems. 

People living with severe mental illness experience a disproportionate burden of physical disease. On average, individuals with severe mental illness die 15–20 years earlier than the general population, much of this gap driven by preventable cardiovascular and metabolic conditions. Their risk of cardiovascular disease is markedly elevated, contributing to poorer long-term health outcomes. 

Professor Smith says that separating mental and physical health has limited progress in treatment: 

“We’ve always known that weight gain and metabolic problems are a major issue for people with severe mental illness, and they’re not entirely explained by medication. There are deeper biological links that we need to understand. If we can do that, we can begin to develop new metabolic approaches to treatment, which is a genuinely novel direction for psychiatry.” 

Professor Daniel Smith

Professor Smith leads The Hub for Metabolic Psychiatry – one of six centres within the UKRI Mental Health Platform established to investigate these connections. The Hub brings together clinicians, geneticists, data scientists and lived-experience partners to study how metabolic dysfunction relates to psychiatric illness. 

Its interconnected workstreams span biomarker discovery, health informatics, genomics, deep phenotyping and patient co-production – an integrated model designed to translate biological insight into clinical innovation. 

“For too long, mental and physical health have been treated as separate systems,” says Professor Smith. “In reality, they are deeply interconnected. Metabolic psychiatry allows us to study those links rigorously and translate what we learn into treatments that improve both mental and physical outcomes.”  

From pilot findings to clinical testing

Iain’s early experiences formed the basis of Edinburgh’s pilot clinical study examining ketogenic dietary therapy in bipolar disorder – one of the first structured investigations of its kind. 

27 participants enrolled in the eight-week trial, with 20 completing the intervention. Participants tracked daily ketone levels alongside measures of mood, anxiety and impulsivity, while researchers monitored metabolic health and brain chemistry. 

The study identified a possible association between higher ketone levels and improved mood stability, alongside reductions in anxiety and impulsivity. Participants also experienced measurable physical health benefits, including an average weight loss of approximately 4 kilograms. 

Brain imaging conducted on some of the study participants revealed reductions in glutamate – an excitatory neurotransmitter implicated in mood dysregulation, suggesting ketosis may influence underlying neurobiological pathways.* 

The exploratory pilot study demonstrated that ketogenic therapy was feasible, safe and associated with potentially clinically meaningful changes, providing a rationale for larger randomised-controlled trials.  

The next stage is now underway. An £8 million Wellcome Trust-funded randomised controlled trial called ENERGISE-BD that will compare a ketogenic dietary intervention with the NHS EatWell dietary framework in people experiencing bipolar depression. The study will test whether metabolic approaches deliver measurable clinical benefit under controlled conditions. 

“We are delighted by Wellcome’s investment in this clinical trial comparing two nutritional interventions for bipolar depression,” says Professor Smith. “This work builds on our recent feasibility study of the ketogenic diet in bipolar disorder and includes an assessment of how both nutritional approaches might change metabolism within the brain. Should a nutritional approach prove to be helpful for bipolar depression this would be a major breakthrough.” 

Recruitment to the ENERGISE-BD trial starts in October 2026 and will run for four years. In total over 200 patients with bipolar depression will take part.  

Collaboration and shared purpose

The expansion of metabolic psychiatry at Edinburgh reflects collaboration across academic, philanthropic and community partners. 

Early support from the Baszucki Foundation enabled pilot work at a time when the field attracted limited institutional funding, helping researchers gather the evidence necessary to pursue larger-scale investigation. 

Community organisations, including Bipolar Scotland, and the Hub’s Lived Experience Advisory Panel (LEAP) ensure that research priorities reflect patient perspectives. This co-production model shapes study design, knowledge exchange and translation into real-world impact. 

Those living with bipolar disorder have historically made outsized contributions to science, academia, government and the arts, yet bipolar research has been tragically underfunded. Our dream is that by spotlighting and accelerating the work of the most promising researchers in the field, we can bring hope to patients and families who will benefit from transformative new treatments.”

Jan Ellison Baszucki (quoted from Businesswire.com)  

Why this matters

Severe mental illness carries a significant metabolic burden that affects both quality and length of life. Addressing psychiatric symptoms without considering physical health risks leaves an important dimension of care untouched. 

Metabolic psychiatry does not replace established treatments. Instead, it broadens the framework through which mental illness is understood, integrating biological, behavioural and metabolic insight to improve outcomes. Professor Smith explains: 

“Our aim is to understand the biological mechanisms linking metabolism and mental illness. If we succeed, we can begin to predict, prevent and treat severe mental illness in ways that were not previously possible.”  

Looking ahead

The Hub’s workstreams, alongside the Wellcome trial, position Edinburgh within an international effort to understand metabolism’s role in psychiatric illness. 

Researchers are working to identify metabolic biomarkers, refine dietary and metabolic interventions, and explore how sleep, circadian rhythms and energy regulation intersect with mental health. 

The ambition is to expand the scope of psychiatry beyond neurotransmission alone to include other fundamental aspects of biology, recognising that mental health is inseparable from the biological systems that sustain the body. 

To find out more about supporting research into mental health, contact Brigid Harty (Head of Philanthropy, Health) at Brigid.Harty@ed.ac.uk 

Related links 

The Hub for Metabolic Psychiatry 

*Additional sources: 
https://www.nature.com/articles/s41380-024-02431-w 

https://www.nature.com/articles/s41398-022-02122-6 

Main image credit: Nadiia Borovenko via Getty Images