Ketogenic Dietary Therapy in Serious Mental Health Disorders

Written by:    Helen Grossi RD
Matthew’s Friends Medical Advisory Board
Research Dietitian in Scotland

In recent years there has been an increased interest in the use of Ketogenic Diet Therapy (KDT) in the management of serious psychiatric conditions such as Bipolar Disorder, Schizophrenia and Major Depressive Disorder. These conditions have a severe impact on the person and their families, friends and other social networks. Research has shown that these conditions share some metabolic features known to be targeted by KDT in epilepsy management, such as difficulties in metabolising glucose, imbalances in neurotransmitters in the brain, cellular stress and inflammation.

Bipolar Disorder:

Bipolar Disorder is a serious mental illness which is estimated to affect 1–2% of the population. This disorder usually begins in early adulthood. It is characterised by severe changes in mood, energy and thought which affects how people function. Symptoms during a manic episode can include grandiosity, higher energy levels, with less need for sleep and increased emotional expressions. Depressive episodes can include changes in appetite, feelings of worthlessness, fatigue and frequent suicidal thoughts. The reasons for developing Bipolar Disorder are not well understood, and current treatments and prevention strategies are not always effective, and may cause other metabolic side effects so, there is a great need to find effective new interventions.

Schizophrenia:

Schizophrenia is another serious mental illness affecting approximately 1% of people in the UK. It can affect how people think, feel and behave. Other symptoms include hallucinations, delusions, disorganised thinking and impaired functioning.

What are Ketogenic Dietary Therapies?

Ketogenic Dietary Therapies (KDT) are high fat, low carbohydrate, adequate protein regimes that can be provided by using the traditional classical or medium chain triglyceride (MCT) ketogenic diets, or by more liberal dietary protocols such as the modified ketogenic diet (MKD) and low glycaemic index treatment (LGIT). MKD therapies are generally used in the adult mental health trials. KDT’s are designed to produce a similar metabolic response to starvation (without the need to starve the body), with ketone bodies acetoacetate and -hydroxybutyrate becoming the main brain energy source where there is an inadequate glucose supply. It’s thought that KD may provide more stable energy production and neuroprotective effects. This metabolic shift can help overcome issues of glucose metabolism and insulin resistance.

What happens to the metabolism in severe mental illness:

Abnormal glucose metabolism is common in people with Bipolar Disorder, Schizophrenia, and other mental health conditions with a higher number of people having insulin resistance and Type 2 Diabetes. It is possible that too much insulin may affect the production of energy in the mitochondria (which are like the batteries) in the brain cells. Several of the drugs used to treat these severe mental illnesses affect metabolism and can cause weight gain. It is thought this may be linked to a worsening of the underlying dysfunction.

Why use a Ketogenic Diet Therapy in severe mental illness?

Ketogenic Diet Therapy has been shown in recent Pilot Studies to improve energy, mood and quality of life while reducing impulsivity and anxiety. There might also be improvements in metabolic dysfunction such as insulin resistance. There are also clinical parallels between Bipolar Disorder and epilepsy, such as pharmacological treatments that are effective. This may show that there are similarities in the underlying disease processes. The use of Ketogenic Diets in the treatment of complex epilepsy suggests that it might be worth exploring this in the treatment of serious mental health disorders through appropriate clinical trials.

Previously, case series were published describing patients who had either Bipolar Disorder or Schizophrenia, which show the benefit of using Ketogenic Diet Therapy, but there were no large studies. More recently, there have been two pilot studies published in the UK and in the USA. The first has shown that Ketogenic Diet is feasible and safe in people with Bipolar Disorder. From the same study (published separately), it was suggested that there may be an association between ketone levels in the blood with positive changes in daily mood, energy, impulsivity and anxiety. The second study also suggested improvements in psychiatric and metabolic outcomes in people with Bipolar Disorder and Schizophrenia.

These studies of the use of Ketogenic Diet Therapy in severe mental illnesses are very encouraging. There are currently several randomised control (RCT’s) either being planned or conducted looking at this, as well as evaluating cognition using spectroscopy and further studying mitochondrial disfunction.

References

  1. Yoshimi N, Futamura T, Bergen SE, Iwayama Y, Ishima T, Sellgren C, et al. Cerebrospinal fluid metabolomics identifies a key role of isocitrate dehydrogenase in bipolar disorder: evidence in support of mitochondrial dysfunction hypothesis. Mol Psychiatry 2016; 21(11): 1504–10.
  2. Łojko D, Owecki M, Suwalska A. Impaired glucose metabolism in bipolar patients: the role of psychiatrists in its detection and management. Int J Environ Res Public Health 2019; 16(7): 1132.
  3. Campbell IH, Campbell H. Ketosis and bipolar disorder: controlled analytic study of online reports. BJPsych Open 2019; 5(4): e58.
  4. Campbell I, Campbell H. Mechanisms of insulin resistance, mitochondrial dysfunction and the action of the ketogenic diet in bipolar disorder. Focus on the PI3K/AKT/HIF1-a pathway. Med Hypotheses 2020; 145: 110299.
  5. Campbell IH, Campbell H, Smith DJ. Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder. Transl Psychiatry 2022; 12(1): 350.
  6. Brietzke E, Mansur RB, Subramaniapillai M, Balanzá-Martínez V, Vinberg M, González-Pinto A, et al. Ketogenic diet as a metabolic therapy for mood disorders: evidence and developments. Neurosci Biobehav Rev 2018; 94:11–6.
  7. Martin‐McGill, Kirsty J; Jackson, Cerian F; Bresnahan, Rebecca; Levy, Robert G; Cooper, Paul N; Martin‐McGill, Kirsty J. Ketogenic Diets for drug resistant epilepsy. Cochrane database of systematic reviews, 2018-11, Vol.2018 (11), p.CD001903
  8. Treatment: Epilepsy. NHS, 2023 Available from: https://www.nhs.uk/ conditions/epilepsy/treatment/ [cited 6 Feb 2023].
  9. Branco AF, Ferreira A, Simões RF, Magalhães-Novais S, Zehowski C, Cope E, et al. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest 2016; 46(3): 285–98.
  10. Phelps JR, Siemers SV, El-Mallakh RS. The ketogenic diet for type II bipolar disorder. Neurocase 2013; 19(5): 423–6. 14
  11. Danan A, Westman EC, Saslow LR, EdeG. The ketogenic diet for refractory mental illness: a retrospective analysis of 31 inpatients. Front Psychiatry 2022; 13: 951376.
  12. Needham, Nicole; Campbell, Iain H; Grossi, Helen; Kamenska, Ivana; Rigby, Benjamin P; Simpson, Sharon A.; McIntosh, Emma; Bahuguna, Pankaj; Meadowcroft, Ben; Creasy, France; Mitchell-Grigorjeva, Maja; Norrie, John; Thompson, Gerard; Gibbs, Melissa C.; McLellan, Ailsa; Fisher, Cheryl; Moses, Tessa; Burgess, Karl; Brown, Rachel; Thrippleton, Michael J.; Campbell, Harry; Smith, Daniel J. Pilot study of a Ketogenic Diet in Bipolar Disorder. BJPsych open, 2023-10, Vol.9 (6), p.e176, Article e17
  13. Needham, Nicole ; Campbell, Iain H.; Grossi, Helen; Kamenska, Ivana; Rigby, Benjamin P.; Simpson, Sharon A.; McIntosh, Emma; Bahuguna, Pankaj; Meadowcroft, Ben; Creasy, Frances; Mitchell-Grigorjeva, Maja; Norrie, John; Thompson, Gerard; Gibbs, Melissa C.; McLellan, Ailsa; Fisher, Cheryl; Moses, Tessa; Burgess, Karl; Brown, Rachel; Thrippleton, Michael J.; Campbell, Harry; Smith, Daniel J. A Pilot study of a Ketogenic Diet in Bipolar Disorder: Clinical, Metabolic and magnetic Resonance Spectroscopy findings. BJPsych open, 2025- Feb;1192) Article e34
  14. Sethi S, Wakeham D, Ketter T, Hooshmand F, Bjornstad J. Richards B, Westman E, Krauss RM, Saslow L. Ketogenic Diet Intervention on Metabolic and Physical Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry Research 2024 Vol 335 115866

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