19 Dec Schizophrenia: Low Carb Ketogenic Diet May Improve Symptoms

Dr. Zoltan Sarnyai

MedicalResearch.com Interview with:
Zoltan Sarnyai, M.D., Ph.D.
Associate Professor of Pharmacology
Head, Laboratory of Psychiatric Neuroscience
Australian Institute of Tropical Health and Medicine (AITHM)
Comparative Genome Centre
Centre for Biodiscovery and Molecular Development of Therapeutics
James Cook University
Townsville, Australia

Medical Research: What is the background for this study?

Dr. Sarnyai: Schizophrenia has long been conceptualized as a disease contributed by the increased activity of the neurotransmitter system that provides dopamine for the brain. All clinically used antipsychotic drugs inhibit dopamine transmission in the brain by blocking dopamine receptors. These drugs have only a limited efficacy on a certain set of symptoms associated with schizophrenia. More recent research has uncovered that abnormal glucose and energy metabolism in the brain may contribute in the development of schizophrenia. This is not altogether surprising considering that our brain is using a disproportionately high amount of glucose to fuel neurotransmission (cell-to-cell communication in the brain), to maintain normal electrical activity of nerve cells and to deal with damaging free oxygen radicals. Therefore, even relatively small changes in the machinery that is required to provide energy for the brain cells can have very significant impact on brain function. In fact, recent studies have identified altered expression of genes and proteins that are responsible for enzymatic breakdown of glucose and proper handling of the metabolites to create the energy-rich molecule ATP. In addition, recent research shows decreased number and impaired function of the mitochondria, the powerhouses of the cell, in the brain of individuals with schizophrenia. 

These recent results that show abnormal energy metabolism in schizophrenia raise the possibility of targeting metabolic pathways for therapeutic benefit in this condition. Ketogenic diet provides and alternative source of energy to the brain through fatty acids. Furthermore, since this diet is very low in carbohydrates, almost all the energy needs of the cells comes from breaking down fat (fatty acids) as opposed to glucose. This can circumvent the classic glucose metabolic pathways that maybe impaired in the disease. Also, breaking down fatty acids produces 40% more of the energy-rich molecule ATP than breaking down the carbohydrate glucose. Altogether, ketogenic diet may provide extra energy and can help neurotransmission in the brain, leading to the improvement of neurobiological processes underlying schizophrenia.

Medical Research: What are the main findings?

Dr. Sarnyai: In our experiments we used a well-established animal model of schizophrenia that is based on human observation that certain drugs, such as phencyclidine (Angel dust) and ketamine (Special K) can lead to psychosis. We used a drug that acts through the same mechanism as these and we induced a set of behaviours in mice that are analogous to the certain symptoms in schizophrenia, such as psychomotor hyperactivity, stereotyped behaviours, impaired social interaction and impaired working memory (important process for reasoning, comprehension, learning and memory updating). When animals were on ketogenic diet for three weeks none of these behaviours appeared. This is quite remarkable as clinically used antipsychotics are usually effective in controlling psychosis but do very little, if anything at all, with impaired social interactions and working memory/cognitive deficits.

Medical Research: What should clinicians and patients take away from your report?

Dr. Sarnyai: These results are quite novel and still preliminary, awaiting for replication by other groups and extension by using other animal models. However, they emphasize the importance of dietary factors in the management of schizophrenia. Studies starting to emerge showing that a healthy diet has benefits in symptom management. Ketogenic diet, however, should potentially be considered as a therapeutic diet. It is quite prescriptive with regards to the high fat and very low carbohydrate content and it may not easy to follow. However, we know that is safe in the long term as ketogenic diet has long been used in the management of drug-resistant epilepsies in children worldwide. Ketogenic diet may have another set of benefits in the management of schizophrenia. Some of the drugs used clinically lead to excessive weight gain, insulin resistance, metabolic syndrome and resultant deleterious cardiovascular consequences. Ketogenic diet maybe able to counteract these metabolic side effects as well. We know from research in ketogenic diet is used for weight management purposes that it has such beneficial effects. However, we do not yet have the direct scientific evidence to support that.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Sarnyai: A number of experiments are currently under way in our laboratory to extend our knowledge on the effect of ketogenic diet in schizophrenia. We are using other, non-pharmacological, animal models to provide converging evidence for the efficacy of ketogenic diet. We are also conducting experiments to understand the molecular changes that take place in the brain in response to the ketogenic diet in an animal model of schizophrenia. These experiments can provide us with novel molecular targets we can use to develop more targeted and better medication with less side-effects to treat schizophrenia at its core.

Citation:

Ann Katrin Kraeuter, Heather Loxton, Bruna Costa Lima, Donna Rudd, Zoltán Sarnyai. Ketogenic diet reverses behavioral abnormalities in an acute NMDA receptor hypofunction model of schizophrenia.
Schizophrenia Research, 2015; 169 (1-3): 491

DOI:10.1016/j.schres.2015.10.041
Zoltan Sarnyai, M.D., Ph.D. (2015). Schizophrenia: Low Carb Ketogenic Diet May Improve Symptoms 

Last Updated on December 19, 2015 by Marie Benz MD FAAD