Schizophrenia – Ketogenic diet brings new hope for the treatment resistant
Can a schizophrenia diet be a useful medical intervention? The exact causes of schizophrenia and schizoaffective disorder are unknown. The predominant theory has been related to excessive dopamine activity (dopamine is a neurotransmitter in the brain), given that all antipsychotic medications block the dopamine-D2 receptors in the brain. However, treatment outcomes for most people with schizophrenia using antipsychotic medications leave much room for improvement. One study of over 6,000 patients with schizophrenia found that only 4% achieved a full recovery, defined as symptom remission, adequate quality of life, and functional recovery.1 These patients were all getting treatment, yet still suffering and not able to get back to their old lives. We need better treatments for schizophrenia!
Recent research suggests that abnormalities in glucose tolerance and insulin resistance may play a role in schizophrenia.2 3 Mitochondrial dysfunction and disturbances in energy metabolism have also been associated with schizophrenia and bipolar disorder, meaning the brain or certain parts of the brain may not be getting enough energy, at least from glucose.4 Overall, there appears to be a correlation between schizophrenia and the body’s impaired ability to process glucose/sugar for energy. The ketogenic diet forces the body and brain to begin using ketones for energy instead of glucose, possibly bypassing some of these abnormalities. The ketogenic diet also has numerous other effects on the body and brain, such as changes in neurotransmitter systems and decreased inflammation, that may also play a role in a therapeutic effect.
Is there any evidence that the ketogenic diet actually works for schizophrenia?
Yes. First, there’s an animal study suggesting a clear effect.
A 2015 study of a mouse model of schizophrenia (the type of study required in the approval process of all antipsychotic medications) showed that the ketogenic diet reversed many pathological symptoms associated with schizophrenia, including positive symptoms (things like hallucinations or delusions), negative symptoms (things like a lack of motivation or social isolation), and cognitive symptoms (such as impaired concentration or inability to think clearly).5
But what about people? Is there any evidence in real people suffering from schizophrenia or schizoaffective disorder?
Yes. There are small studies and case studies suggesting a beneficial effect, at least in some people, which should be considered preliminary evidence (definitive evidence would be a blinded, randomized, controlled trial).
The first study dates back to 1965! Pacheco et al6 reported in the American Journal of Psychiatry that they put 10 hospitalized women with schizophrenia on the ketogenic diet, and that they noticed improvement in symptoms as early as 2 weeks after starting the diet, and that the symptoms worsened again when they stopped the diet. There were many methodological limitations to this study, as was often the case in research in the 1960’s, but nonetheless, they reported a positive effect.
In 2009, Doctors. Kraft and Westman from Duke University described the case of a 70 year old woman with schizophrenia who had been diagnosed with the disorder since age 17. She had daily auditory and visual hallucinations. After starting a ketogenic, low-carbohydrate diet, she had complete resolution of her hallucinations for over one year, despite at least 3 episodes of breaking her diet.
Most recently, in 2017, our own Chris Palmer, MD published a research article in Schizophrenia Research (8) describing two case studies of people with schizoaffective disorder who both experienced dramatic reductions in their symptoms when they were in ketosis on the ketogenic diet. They each experienced improvement in both positive and negative symptoms, meaning their hallucinations and delusions were significantly reduced, and they felt improved mood, energy, and motivation, and improved social functioning. Both of these patients had tried numerous standard treatments, including multiple antipsychotic medications, including clozapine (often considered the “gold standard” treatment of last resort), and the woman had also tried an extended course of electroconvulsive therapy (ECT or in the old days referred to as “electric shock treatments”), and none of these treatments had produced improvement to the degree they experienced with the ketogenic diet.
Remission dependent on ketone levels
Interestingly, when each of them stopped the diet, they experienced a relapse of psychotic symptoms, and then the symptoms remitted or declined again when they resumed the ketogenic diet. These patients were doing a strict ketogenic diet, NOT the popular weight loss version of the diet. Ketone levels were directly correlated with symptom improvement. Finally, on top of dramatic symptom improvement, they also both lost significant amounts of weight (the male patient lost more than 110 pounds), had improvements in other health risk factors (such as cholesterol and triglyceride levels), and have kept off the weight for over two years now!
Thanks for making us #1 in Medscape Psychiatry!
In another article, Zoltán Sarnyai, Ann-Katrin Kraeuter, and our own Chris Palmer, MD reviewed recent research on the effectiveness of treating Schizophrenia with the ketogenic diet in clinical settings. (9) They examined both pre-clinical models and in patients with schizophrenia
Ketogenic diet may present a novel therapeutic approach through restoring brain energy metabolism in schizophrenia.Chris Palmer, MD Et al.
Thank you psychiatry for being open to reading about a new metabolic treatment modality! This article was recently #1 for the month in Medscape psychiatry.
Should people with schizophrenia try the ketogenic diet on their own?
As much as I wish it were that simple, it’s not. First of all, the version of the diet that appears to work for serious psychiatric disorders is the strict medical version (3:1 or 4:1 ratio), the same one used in treating pediatric epilepsy. This version of the diet should be medically prescribed and monitored, as it is very difficult to do and has serious risks. Levels of ketones, glucose, and body weight all impact the effectiveness of the diet.
Additionally, medications often need to be adjusted, as new side effects can emerge when people are in ketosis, and some medications can interfere with the effectiveness of the ketogenic diet by increasing blood glucose levels and preventing ketosis, so they may need to be safely reduced or stopped. Adjusting psychiatric medications can sometimes be very dangerous, and should only be done with medical supervision and monitoring. Finally, when starting the ketogenic diet, people can experience hypoglycemia, low blood pressure, weakness, dizziness, and other worrisome symptoms, which all need to be monitored and safely managed by a skilled medical team.
Want more case study details?
- Doris’s chronic Schizophrenia put into remission bringing hope to many (8)
- Ketogenic diet helps Ecuadorian twins improve their schizophrenic symptoms (10)
More on the ketogenic diet – mental health – and metabolic connections
- Can a ketogenic diet successfully treat Bipolar Disorder?
- The ketogenic diet helps you address the metabolic challenge of losing weight
- Ketogenic diet lowers glucose for diabetics
- Our research and how to participate
- Continuing education for professionals
- Novick D, Haro JM, Suarez D, Vieta E, Naber D. Recovery in the outpatient setting: 36-month results from the Schizophrenia Outpatients Health Outcomes (SOHO) study. Schizophrenia Research 2009 Mar;108(1-3):223-30. doi: 10.1016/j.schres.2008.11.007. Epub 2008 Dec 13.
- Perry, B.I., McIntosh, G.,Weich, S., Singh, S., Rees, K., 2016. The association between first episode psychosis and abnormal glycaemic control: systematic review and metaanalysis. Lancet Psychiatry 3, 1049–1058.
- Harris, L.W., Guest, P.C., Wayland, M.T., Umrania, Y., Krishnamurthy, D., Rahmoune, H., Bahn, S., 2013. Schizophrenia: metabolic aspects of aetiology, diagnosis and future treatment strategies. Psychoneuroendocrinology 38 (6), 752–766.
- Clay, H.B., Sillivan, S., Konradi, C., 2011. Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia. Int. J. Dev. Neurosci. 29, 311–324.
- Kraeuter, A.K., Loxton, H., Lima, B.C., Rudd, D., Sarnyai, Z., 2015. Ketogenic diet reverses behavioral abnormalities in an acute NMDA receptor hypofunction model of schizophrenia. Schizophr. Res. 169, 491–493.
- Pacheco et al; A pilot study of the ketogenic diet in schizophrenia. Am J Psychiatry 1965, 121:1110-1111.
- Kraft and Westman; Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutrition & Metabolism 2009, 6:10
- Palmer CM. Ketogenic diet in the treatment of schizoaffective disorder: Two case studies. Schizophrenia Research 2017 Nov; 189:208 – 209. doi: 10.1016/j.schres.2017.01.053. Epub 2017 Feb 3.
- Sarnyai, Z., Kraeuter, A.-K., & Palmer, C. M. (2019). Ketogenic diet for schizophrenia: Clinical implication. Current Opinion in Psychiatry, 32(5). Retrieved from https://journals.lww.com/co-psychiatry/Fulltext/2019/09000/Ketogenic_diet_for_schizophrenia__clinical.6.aspx
- Palmer CM, Gilbert-Jaramillo J, Westman EC. The ketogenic diet and remission of psychotic symptoms in schizophrenia: Two case studies. Schizophrenia Research. 2019 Jun; 208:439-440. doi: 10.1016/j.schres.2019.03.019. Epub 2019 Apr 6.