The ketogenic diet in schizophrenia
DOI:
https://doi.org/10.12775/JEHS.2023.43.01.012Keywords
Schizophrenia, Schizoaffective, Ketogenic, Diet, Ketones, Ketosis, GABA-ergic activityAbstract
Schizophrenia is a mental illness that manifests itself in the second or third decade of life with no coherent aspect. The primary pharmacological therapy is antipsychotic medication, which mostly work by suppressing the activity of dopamine. Unluckily, many of schizophrenic patients experience hardship from severe positive or negative symptoms that can not be completely treated with available treatment. Last theory of schizophrenia mechanism contain systemic and central proinflammatory process, in brain glutamatergic neurotransmission and impaired systemic and cerebral energy metabolism. Ketogenic diet is firm controlled high-fat, low protein, low-carbohydrate diet, with lipid to non lipid ratio 4:1. Main mechanism is to cause ketosis. The situation in which ketones bodies are used as a substrate to generate energy in the organism. It could be that a ketogenic diet could help to compensate for the imbalance of GABA levels in schizophrenic brain. The ketogenic diet as an addition to drug treatment, hopefully may offer therapeutic opportunities to better result of the disease concerning symptomatology and preventing the gain of weight, due to some medication side effects or comorbidities.
References
Picchioni MM, Murray RM. 2007 Jul Schizophrenia. BMJ. 14;335(7610):91-5.
van Os J, Kapur S. 2009.Schizophrenia. Lancet; 374:635–645.
Owen MJ, Sawa A, Mortensen PB.2016. Schizophrenia. Lancet; 388:86–97.
Włodarczyk A, Szarmach J, Cubala WJ, Wiglusz MS. 2007.Benzodiazepines in combination with antipsychotic drugs for schizophrenia: gaba-ergic targeted therapy, Psychiatria Danubi, 2017; Vol. 29, Suppl. 3, pp 345-348. PubMed: 28953788.
Coyle JT, Basu A, Benneyworth M, Balu D, Konopaske G. 2012 Glutamatergic synaptic dysregulation in schizophrenia: therapeutic implications. Handb Exp Pharmacol. (213):267-95
Thomas EHX, Bozaoglu K, Rossell SL, Gurvich C.2017 The influence of the glutamatergic system on cognition in schizophrenia: A systematic review. Neurosci Biobehav Rev. ;77:369-387.
Pillinger T, D’Ambrosio E, McCutcheon R, Howes OD. 2018 Is psychosis a multi-system disorder? A meta-review of central nervous system, immune, cardiometabolic, and endocrine alterations in first-episode psychosis and perspective on potential models. Mol Psychiatry.24(6):776-794
Muller N.2018 Inflammation in schizophrenia: pathogenetic aspects and therapeutic considerations. Schizophr Bull; 44:973–982.
Sullivan CR, O’Donovan SM, McCullumsmith RE, Ramsey A. 2018 Defects in bioenergetic coupling in schizophrenia. Biol Psychiatry; 83:739–750.
Zuccoli GS, Saia-Cereda VM, Nascimento JM, Martins-de-Souza D. 2017 The energy metabolism dysfunction in psychiatric disorders postmortem brains: focus on proteomic evidence. Front Neurosci; 11:493.
Paoli A, Rubini A, Volek JS, Grimaldi KA. 2013 Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr.;67(8):789-96.
Yancy WS Jr, Foy M, Chalecki AM, Vernon MC, Westman EC. 2005 A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutr Metab (Lond).1;2:34.
Bostock ECS, Kirkby KC, Taylor BVM. 2017 The Current Status of the Ketogenic Diet in Psychiatry, Front Psychiatry;.8:43.
Dashti HM, Mathew TC, Hussein T, Asfar SK, Behbahani A, Khoursheed MA, Al-Sayer HM, Bo-Abbas YY, Al-Zaid NS. 2004 Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol.;9(3):200-5.
Kwiterovich PO Jr, Vining EP, Pyzik P, Skolasky R Jr, Freeman JM. 2003 Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA. Aug 20;290(7):912-20.
Azevedo de Lima P, Prudêncio MB, Murakami DK, de Brito Sampaio LP, Neto AMF, Damasceno NRT. 2017. Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy, Nutrition;33:271-277
Seo JH, Lee YM, Lee JS, Kang HC, Kim HD. 2007 Apr.Efficacy and tolerability of the ketogenic diet according to lipid:nonlipid ratios--comparison of 3:1 with 4:1 diet. Epilepsia.;48(4):801-5.
WOODYATT RT. 1921 OBJECTS AND METHOD OF DIET ADJUSTMENT IN DIABETES. Arch Intern Med (Chic).;28(2):125–141.
Vining EP, Freeman JM, Ballaban-Gil K, Camfield CS, Camfield PR, Holmes GL, Shinnar S, Shuman R, Trevathan E, Wheless JW. 1998 Nov.A multicenter study of the efficacy of the ketogenic diet. Arch Neurol.;55(11):1433-7.
Kossoff EH.. 2008 Nov. International consensus statement on clinical implementation of the ketogenic diet: agreement, flexibility, and controversy. Epilepsia;49 Suppl 8:11-3.
Harris JJ, Jolivet R, Attwell D. 2012 Synaptic energy use and supply. Neuron.; 775:762–777.
Dienel GA. 2019 Brain glucose metabolism: integration of energetics with function. Physiol Rev; 99:949–1045.
Magistretti PJ, Pellerin L. 1999 Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci; 354:1155–1163.
Kann O, Papageorgiou IE, Draguhn A. 2014 Highly energized inhibitory interneurons are a central element for information processing in cortical networks. J Cereb Blood Flow Metab; 34:1270–1282.
Prabakaran S, Swatton JE, Ryan MM, et al. 2004 Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry ; 9:684–697; 43.
Chouinard VA, Henderson DC, Dalla Man C, et al. 2019 Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis. Mol Psychiatry.; 24(10): 1513–1522.
Sullivan CR, Koene RH, Hasselfeld K, et al. 2019 Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia Mol Psychiatry. 9:1319-1328.
Sullivan CR, Mielnik CA, Funk A, et al. 2019 Measurement of lactate levels in postmortem brain, iPSCs, and animal models of schizophrenia. Sci Rep; 9:5087.
Du F, Cooper AJ, Thida T, et al. 2014 In vivo evidence for cerebral bioenergetic abnormalities in schizophrenia measured using 31P magnetization transfer spectroscopy. JAMA Psychiatry ; 71:19–27.
Prince JA, Harro J, Blennow K, et al. 2000 Putamen mitochondrial energy metabolism is highly correlated to emotional and intellectual impairment in schizo-phrenics. Neuropsychopharmacology ; 22:285–292.
Martins-de-Souza D, Maccarrone G, Wobrock T, et al.2010 Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers candidates for schizophrenia. J Psychiatr Res ; 44:1176–1189.
Wesseling H, Chan MK, Tsang TM, et al.2013 A combined metabonomic and proteomic approach identifies frontal cortex changes in a chronic phencyclidine rat model in relation to human schizophrenia brain pathology. Neuropsychopharmacology ; 38:2532–2544.
Ernst A, Ma D, Garcia-Perez I, et al. 2012 Molecular validation of the acute phencyclidine rat model for schizophrenia: identification of translational changes in energy metabolism and neurotransmission. J Proteome Res ; 11:3704–3714.
Maurer I, Zierz S, Moller H-J. 2001 Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia. Schizophr Res; 48:125–136.
Karry R, Klein E, Ben Shachar D. 2004 Mitochondrial complex I subunits expression is altered in schizophrenia: a postmortem study. Biol Psychiatry ; 55:676–684.
Altar CA, Jurata LW, Charles V, et al.2005 Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts. Biol Psychiatry ; 58:85–96.
Clay HB, Sillivan S, Konradi C. 2011 Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia. Int J Dev Neurosci; 29:311–324.
Robicsek O, Karry R, Petit I, et al. 2013 Abnormal neuronal differentiation and mitochondrial dysfunction in hair follicle-derived induced pluripotent stem cells of schizophrenia patients. Mol Psychiatry ; 18:1067–1076.
Ben-Shachar D. 2017 Mitochondrial multifaceted dysfunction in schizophrenia;complex I as a possible pathological target. Schizophr Res; 187:3–10.
Holper L, Ben-Shachar D, Mann JJ. 2019 Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder,schizophrenia, Alzheimer disease, and Parkinson disease. Neuropsychopharmacology ; 44:837–849.
Bergman O, Karry R, Milhem J, Ben-Shachar D. 2020 NDUFV2 pseudogene (NDUFV2P1) contributes to mitochondrial complex I deficits in schizophrenia.Mol Psychiatry ;25(4):805-820.
Robicsek O, Ene HM, Karry R, et al.2018 Isolated mitochondria transfer improves neuronal differentiation of schizophrenia-derived induced pluripotent stem cells and rescues deficits in a rat model of the disorder. Schizophr Bull ;44:432–442.
Paoli A, Rubini A, Volek JS, Grimaldi KA. 2013 Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr; 67:789–796.
Kennedy AR, Pissios P, Otu H, et al. 2007 A high-fat, ketogenic diet induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab ;292:E1724–E1739.
Achanta LB, Rae CD. 2017 Beta-hydroxybutyrate in the brain: one molecule, multiple mechanisms. Neurochem Res ; 42:35–49.
Verrotti A, Iapadre G, Pisano S, Coppola G. 2017 Ketogenic diet and childhood neurological disorders other than epilepsy: an overview. Exp Rev Neurother ; 17:461–473.
Cheng N, Rho JM, Masino SA.2017 Metabolic dysfunction underlying autism spectrum disorder and potential treatment approaches. Front Mol Neurosci ; 10:34.
Hasan-Olive MM, Lauritzen KH, Ali M, et al.2019 A ketogenic diet improves mitochondrial biogenesis and bioenergetics via the PGC1alpha-SIRT3- UCP2 axis. Neurochem Res ; 44:22–37.
Branco AF, Ferreira A, Simoes RF, et al. 2016 Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest; 46:285–298.
Vidali S, Aminzadeh S, Lambert B, et al. 2015 Mitochondria: the ketogenic diet–a metabolism-based therapy. Int J Biochem Cell Biol;63:55–59.
Rogawski MA, Loscher W, Rho JM. 2016 Mechanisms of action of antiseizure drugs and the ketogenic diet. Cold Spring Harb Perspect Med;2;6(5):a022780.
D’Andrea Meira I, Romao TT, Pires do Prado HJ, et al. 2019 Ketogenic diet and epilepsy: what we know so far. Front Neurosci ; 13:5.
Broom GM, Shaw IC, Rucklidge JJ.2019 Apr The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease. Nutrition. ;60:118-121.
Koppel SJ, Swerdlow RH.2018 Neuroketotherapeutics: a modern review of a century-old therapy. Neurochem Int ; 117:114–125.
Jones C, Watson D, Fone K.2011 Animal models of schizophrenia. Br J Pharmacol 164(4):1162–94.
Kraeuter AK, Loxton H, Lima BC, Rudd D, Sarnyai Z. 2015 Ketogenic diet reverses behavioral abnormalities in an acute NMDA receptor hypofunction model of schizophrenia. Schizophr Res 169(1–3):491.
Kraeuter AK, van den Buuse M, Sarnyai Z. 2018 Ketogenic diet prevents impaired prepulse inhibition of startle in an acute NMDA receptor hypofunction model of schizophrenia. Schizophr Res ; 206:244–250.
Tregellas JR, Smucny J, Legget KT, Stevens KE. 2015 Effects of a ketogenic diet on auditory gating in DBA/2 mice: a proof-of-concept study. Schizophr Res; 169:351–354.
Sarnyai Z, Jashar C, Olivier B.2015 Modeling combined schizophrenia-related behavioral and metabolic phenotypes in rodents. Behav Brain Res ; 276:130–142.
Olivier B, Leahy C, Mullen T, et al. 2001 The DBA/2J strain and prepulse inhibition of startle: a model system to test antipsychotics? Psychopharmacology (Berl); 156:284–290.
Pacheco A, Easterling W, Pryer M.1965 A pilot study of the ketogenic diet in schizophrenia. Am J Psychiatry 121(11):1110–1.
Kraft BD, Westman EC.2009 Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutr Metab (Lond) ; 6:10.
Gilbert-Jaramillo J, Vargas-Pico D, Espinosa-Mendoza T, et al. 2018 The effects of the ketogenic diet on psychiatric symptomatology, weight and metabolic dysfunction in schizophrenia patients. Clin Nutr Metab. 1(1): 1-5
Palmer CM.2017 Ketogenic diet in the treatment of schizoaffective disorder: two case studies. Schizophr Res ; 189:208–209.
Palmer CM, Gilbert-Jaramillo J, Westman EC.2019 The ketogenic diet and remission of psychotic symptoms in schizophrenia: two case studies. Schizophr Res; 208:439–440.
Yudkoff M, Daikhin, Horyn O, Nissim I, Nissim I. 2008 Ketosis and brain handling of glutamate,glutamine, and GABA, Epilepsia. 8(8):73-5.
Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. 2005 Effectiveness of antipsychotic drugs in patients with chronic schizophrenia, N Engl J Med; .22;353(12):1209-23
von Geijer L, Ekelund M,. 2015 Ketoacidosis associated with low-carbohydrate diet in a non-diabetic lactating woman: a case report, J Med Case Rep;. 1;9:224
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Copyright (c) 2023 Maciej Ćwiek, Anna Maria Bigdoń, Przemysław Gorczyca, Mateusz Góra, Adrian Krzysztof Hunek, Martyna Kozłowska, Rafał Kreft, Patryk Sydor, Marcel Wartacz, Aleksander Woźniak
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