A pilot study of a novel metabolic therapy for bipolar disorder.

Let's talk about energy.

Bipolar Disorder (BD) is commonly viewed as a condition caused by an imbalance of neurotransmitters.

But what if the severe circadian and energy shifts in BD point to a more fundamental problem of energy dysregulation in the brain?

There is increasing evidence that the normal function of the cellular engines in neurons "mitochondria" are disrupted in people with BD.

Several lines of evidence indicate that they are unable to effectively utilize glucose -the body's primary fuel source- to create stable energy in the brain.

What would happen if we could provide an alternative fuel source for the bipolar brain?

1. Medications and Ketogenic Diet

Ketogenic Diets (KD) have been in use for nearly 100 years as an effective metabolic therapy for epilepsy [1]. 

A KD is a diet which is high in healthy fats and low in carbohydrate. This kind of diet can shift the 
brain's energy metabolism to run on an alternative fat-derived fuel source known as "ketones".


Bipolar Disorder (BD) is treated by many of the same anti-convulsants used in the treatment of epilepsy, however there have been few studies on the effects of a KD in BD [2].

This study will use brain imaging, metabolomics and mood assessments to find out if the diet may also benefit those with BD.

3. Insulin Resistance and Bipolar Disorder

Over 50% of those with BD have some form of insulin resistance (IR) - a condition where the body cannot use glucose effectively as a fuel source. In many people with BD this leads to type 2 diabetes. Increasing evidence indicates a key role of IR and impaired glucose metabolism in BD. [4].

Ketogenic diets have been demonstrated to reduce or ameliorate IR by reducing blood glucose and insulin levels [5].​

2.  Case Studies of a Ketogenic Diet

There are emerging case studies documenting mood stabilising effects of a ketogenic diet for BD and schizophrenia patients [3].

The case studies describe mood stabilising effects of the diet and improvements in energy; sometimes accompanied by significant weight-loss.

4. Mitochondrial Dysfucntion and Bipolar Disorder

Glucose is converted into a fuel source used by cellular "engines" in the brain called mitochondria. There is considerable evidence that this process is impaired in BD [6].

On a ketogenic diet an alternative mitochondrial "fuel source" called "ketones" are generated and used by the brain [7].

If energy to the brain is restored then this may allow the brain to self-regulate more efficiently, leading to a downstream balance of neurotransmitter levels.


Professor Harry Campbell

Chief Investigator

Professor of Genetic Epidemiology and Public Health,
University of Edinburgh



Professor Daniel Smith

Principal Investigator

Chair of Psychiatry and Head of Division of Psychiatry, University of Edinburgh


Dr. Iain Campbell

Principal Investigator

Global Health PhD 
University of Edinburgh.


Dr. Nicole Needham

Research Coordinator

Centre for Clinical Brain Sciences,
University of Edinburgh

Healthy Food

Join one of the world's first scientific studies of a ketogenic diet for bipolar disorder.

  • Beginning in March 2022, participants will be recruited through the charity Bipolar Scotland and social media channels.

  • A dietician experienced with delivering a ketogenic diet will support participants throughout the 8 week study.

  • Mood will be self-measured and assessed by a psychiatrist throughout the trial.

  • Blood tests and brain imaging will be used to find out how a ketogenic diet affects energy metabolism in the brain and body.

Abstract Background

What is involved?




Weeks of Ketogenic Diet


Carbohydrate Per Day


of Diet as Healthy Fats

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Apply to join the study here

To apply to become a participant in the study please click below to register your interest.