Background For some time now bipolar disorder (BD) and epilepsy have been treated by some of the same anti-convulsant medications. Researchers have considered the possibility that there may be some shared mechanisms underlying both conditions which these medications act on.
There is another intervention for epilepsy known as the “ketogenic diet” which is only recently gaining interest in relation to psychiatric conditions. It may seem odd to think that a diet could be an effective therapy for such a serious neurological condition as epilepsy, however over nearly a century of clinical use has demonstrated its effectiveness for seizure control. A 2018 meta-analysis shows that on a ketogenic diet 13% of adults achieve seizure freedom and 53% achieve seizure reduction by 50% or more.
The ketogenic diet causes some significant changes in the metabolism and neurochemistry of the brain, which may explain its beneficial effects. The human brain typically derives its energy from “burning” glucose as a primary fuel source. Much of the food we eat is broken down into glucose in the body and this fuels the neurons of the brain. However, there is an alternative fuel supply that the brain can use when we don’t eat for a period of time and we start burning body fat instead of glucose. The molecules that make up this fat-derived fuel are known as “ketones”.
People naturally produce and burn ketones for fuel when there is no source of food to provide the body with glucose. When someone loses weight they are burning some of their body fat stores, and producing ketones in the process which can be used for energy. However, in wealthy societies with nearly unlimited access to food, we rarely reach this natural state of fat-burning and do not receive the benefits it can provide for the brain.
The other way that a state of “ketosis" -where ketones are used for energy- can be achieved is to adhere to a ketogenic diet. On a ketogenic diet, healthy fats become the primary source of calories instead of protein and carbohydrates. When high levels of fat are present in the diet with minimal carbohydrates (< 30 grams per day) the body generates ketones without needing to fast. The body simply burns the fat consumed in the diet instead of existing body fat.
Evidence for An Effect on Bipolar Disorder
Some early evidence for a beneficial effect of a ketogenic diet in bipolar disorder is emerging. A case study was carried out with two bipolar patients who both achieved significant mood stabilisation on the diet. A recent report in Bipolar Disorders journal noted a significant improvement in a bipolar patient. Harvard psychiatrist Dr Chris Palmer has been using ketogenic diets in his practice for over 15 years and has now published several case studies for psychiatric conditions including 2 bipolar-type schizoaffective patients achieving significant mood stabilisation. It is interesting to note that the diet is already being widely used by the online bipolar community; a recent text-mining study identified 165 people posting about the ketogenic diet on bipolar disorder forums with the majority reporting improved mood stabilisation.
If the diet does have a beneficial effect on bipolar disorder why might this occur?
There is increasing recognition in the scientific community that bipolar disorder is accompanied by insulin resistance and its related conditions such as diabetes. Over 50% of people with bipolar disorder have some form of insulin resistance. Insulin resistance refers to the breakdown of the body’s ability to process glucose effectively. This can occur after being exposed to prolonged high levels of glucose and insulin due to diet, lifestyle and/or genetic factors. In such cases the ketogenic diet both reduces glucose levels in the body and introduces an alternative fuel source "ketones" for cells and neurons which cannot utilise glucose effectively.
The brain generates energy from glucose by processing it and then "burning" the product in cellular “engines” known as mitochondria. There is now substantial evidence that the mitochondria of people with bipolar disorder are not as efficient at generating energy from glucose as an average person. The brain consumes a large amount of the body’s energy and is very sensitive to any change in energy supply. When mitochondria are not functioning correctly and producing stable levels of energy for the brain, this may diminish the brain’s ability to regulate neurochemistry and keep the brain in a stable state.
One of the World’s First Pilot Trials of The Ketogenic Diet for Bipolar Disorder is Taking Place in Edinburgh A team at Edinburgh University led by Professors Harry Campbell, Daniel Smith and Dr. Iain Campbell will partner with Bipolar Scotland to be one of the first in the world to investigate the ketogenic diet for bipolar disorder. The study is funded by The Bazucki Brain Trust established by philanthropists Jan Ellison Baszucki and David Baszucki. In a businesswire.com article Jan described the motivation behind their work: “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.”
Recruitment for the trial is expected to begin in March 2022, you can register interest in joining by sending a message through the Contact page on this website. This study represents a unique opportunity for people with bipolar disorder to try a new therapy and gain new scientific insight into the role of brain energy metabolism in bipolar disorder. If trials of metabolic approaches such as these prove effective, it may open up a new field of research into how to understand and treat bipolar disorder.
Dr. Iain Campbell