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Metabolic Psychiatry

While metabolic psychiatry is an emerging field, interest is increasing and it is experiencing rapid growth with a number of recent publications. The connection of mental health disorders with metabolic health, along with the utilisation of medications common in epilepsy treatment, reflect neurometabolic pathways as influential in managing these conditions.

Studies listed include diets favouring whole foods or avoiding potential trigger foods. There are a number of features that may connect the conditions, e.g., nutrient sufficiency, insulin resistance, metabolic syndrome, hormonal responses (ghrelin/leptin), and brain glucose hypometabolism/insulin signalling issues which support the potential role of nutritional interventions.

The significant burden of metabolic syndrome in these patients, along with the possible role of drug side effects, could indicate the benefit of therapeutic carbohydrate restriction as an independent consideration. 

Due to the therapeutic effect of carbohydrate restriction, medical supervision is advised when adopting this approach, as reflected in the following article: Ede G (Author), Scher B (Medical review) Low Carb and Mental Health: Getting Started & Managing Medications. Diet Doctor.

Mental Health

Reviews

  1. Dietch, D.M. et al. (2023) ‘Efficacy of low carbohydrate and ketogenic diets in treating mood and anxiety disorders: systematic review and implications for clinical practice’, BJPsych Open, 9(3), p. e70. Available at: https://doi.org/10.1192/bjo.2023.36.
  2. Danan, A. et al. (2022) ‘The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients’, Frontiers in Psychiatry, 13, p. 951376. Available at: https://doi.org/10.3389/fpsyt.2022.951376.
  3. Omori, N.E. et al. (2023) ‘Exploring the role of ketone bodies in the diagnosis and treatment of psychiatric disorders’, Frontiers in Psychiatry, 14, p. 1142682. Available at: https://doi.org/10.3389/fpsyt.2023.1142682.
  4. Sethi S, Ford JM. The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review. Journal of Psychiatry and Brain Science. 2022;7(5). doi:10.20900/jpbs.20220009
  5. Mentzelou, M. et al. (2023) ‘The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice’, Nutrients, 15(10), p. 2270. Available at: https://doi.org/10.3390/nu15102270.
  6. Tillery EE, Ellis KD, Threatt TB, Reyes HA, Plummer CS, Barney LR. The use of the ketogenic diet in the treatment of psychiatric disorders. Mental Health Clinician. 2021;11(3):211-219. doi:10.9740/mhc.2021.05.211 
  7. Sarnyai Z, Palmer CM. Ketogenic Therapy in Serious Mental Illness: Emerging Evidence. Int J Neuropsychopharmacol. 2020;23(7):434-439. doi:10.1093/ijnp/pyaa036 
  8. Aranburu E, Matias S, Simón E, et al. Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review. Nutrients. 2021;13(6):1894. doi:10.3390/nu13061894
  9. Kovacs Z, D’Agostino D, Diamond DM, Kindy MS, Rogers C, Ari C. Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature. Front Psychiatry. 2019;10. doi:10.3389/fpsyt.2019.00363 
  10. Garcia-Rizo C, Kirkpatrick B, Fernandez-Egea E, Oliveira C, Bernardo M. Abnormal glycemic homeostasis at the onset of serious mental illnesses: a common pathway. Psychoneuroendocrinology. 2016;67:70-75. doi:10.1016/j.psyneuen.2016.02.001
  11. Palmer CM. Diets and Disorders: Can Foods or Fasting Be Considered Psychopharmacologic Therapies? J Clin Psychiatry. 2019;81(1):0-0. doi:10.4088/JCP.19ac12727
  12. Norwitz NG, Dalai SS, Palmer CM. Ketogenic diet as a metabolic treatment for mental illness. Current Opinion in Endocrinology, Diabetes and Obesity. 2020;27(5):269–274. doi:10.1097/MED.0000000000000564 PDF
  13. Operto FF, Matricardi S, Pastorino GMG, Verrotti A, Coppola G. The Ketogenic Diet for the Treatment of Mood Disorders in Comorbidity With Epilepsy in Children and Adolescents. Front Pharmacol. 2020;11. doi:10.3389/fphar.2020.57839
  14. Stone LA, Harmatz ES, Goosens KA. Ghrelin as a Stress Hormone: Implications for Psychiatric Illness. Biological Psychiatry. 2020;88(7):531-540. doi:10.1016/j.biopsych.2020.05.013
  15. Whipp AM, Vuoksimaa E, Korhonen T, et al. Ketone body 3-hydroxybutyrate as a biomarker of aggression. Scientific Reports. 2021;11(1):5813. doi:10.1038/s41598-021-84635-6
Media Links
  1. Dr. Chris Palmer presentation: Brain Energy, The metabolic Theory of Mental Illness (2023).
  2. Georgia Ede MD – What is nutritional and metabolic psychiatry #PHC2023. Public Health Colaboration (2023). 
  3. Metabolic Mind – Dr Bret Scher presents: Brain Energy, Mitochondria, and Mental Health with Dr. Chris Palmer (2023). 
  4. Dr. Shebani Sethi – The Emerging Field of Metabolic Psychiatry – Metabolic Link Ep. 24 (2023). 
  5. BMJ and Swiss Re – Food for Thought 2020 – Food for Mind and Body The Impact of Nutrition on Mental Well Being.; 2020
  6. Dr Ann Childers, Mental Health & Nutrition with Ann Childers : Dr.Pallavi’s Mind & Body Wellness :The Webinar Series.; 2020. 

Depression and Anxiety

Depression

  1. Jeremiah OJ, Cousins G, Boland F, Kirby BP, Ryan BK. Evaluation of the effect of insulin sensitivity-enhancing lifestyle- and dietary-related adjuncts on antidepressant treatment response: A systematic review and meta-analysis. Heliyon. 2020;6(9):e04845. doi:10.1016/j.heliyon.2020.e04845 
  2. Tolkien K, Bradburn S, Murgatroyd C. An anti-inflammatory diet as a potential intervention for depressive disorders: A systematic review and meta-analysis. Clinical Nutrition. 2019;38(5):2045-2052. doi:10.1016/j.clnu.2018.11.007
  3. Shamshtein, D. and Liwinski, T. (2022) ‘Ketogenic Therapy for Major Depressive Disorder: A Review of Neurobiological Evidence’, Recent Progress in Nutrition, 2(1), pp. 1–1. doi:10.21926/rpn.2201003.
  4. Setayesh L, Ebrahimi R, Pooyan S, Yarizadeh H, Rashidbeygi E, Badrooj N, et al. The possible mediatory role of adipokines in the association between low carbohydrate diet and depressive symptoms among overweight and obese women. PloS one. 2021;16(9). doi:10.1371/journal.pone.0257275
  5. Arab A, Mehrabani S, Moradi S, Amani R. The association between diet and mood: A systematic review of current literature. Psychiatry Research. 2019;271:428-437. doi:10.1016/j.psychres.2018.12.014 ABSTRACT
  6. Ren M, Zhang H, Qi J, et al. An Almond-Based Low Carbohydrate Diet Improves Depression and Glycometabolism in Patients with Type 2 Diabetes through Modulating Gut Microbiota and GLP-1: A Randomized Controlled Trial. Nutrients. 2020;12(10):3036. doi:10.3390/nu12103036
  7. Jacka FN, O’Neil A, Opie R, et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med. 2017;15. doi:10.1186/s12916-017-0791-y 
  8. Parletta N, Zarnowiecki D, Cho J, et al. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutritional Neuroscience. 2019;22(7):474-487. doi:10.1080/1028415X.2017.1411320
  9. Breymeyer KL, Lampe JW, McGregor BA, Neuhouser ML. Subjective Mood and Energy Levels of Healthy Weight and Overweight/Obese Healthy Adults on High-and Low-Glycemic Load Experimental Diets. Appetite. 2016;107:253-259. doi:10.1016/j.appet.2016.08.008     PDF 
  10. Brinkworth GD, Buckley JD, Noakes M, Clifton PM, Wilson CJ. Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function. Archives of Internal Medicine. 2009;169(20):1873-1880. doi:10.1001/archinternmed.2009.329
  11. Adams, R.N. et al. (2022) ‘Depressive symptoms improve over 2 years of type 2 diabetes treatment via a digital continuous remote care intervention focused on carbohydrate restriction’, Journal of Behavioral Medicine [Preprint]. doi:10.1007/s10865-021-00272-4.
  12. Francis HM, Stevenson RJ, Chambers JR, Gupta D, Newey B, Lim CK. A brief diet intervention can reduce symptoms of depression in young adults – A randomised controlled trial. PLOS ONE. 2019;14(10):e0222768. doi:10.1371/journal.pone.0222768
  13. Stapel, B. et al. (2022) ‘Impact of fasting on stress systems and depressive symptoms in patients with major depressive disorder: a cross-sectional study’, Scientific Reports, 12, p. 7642. doi:10.1038/s41598-022-11639-1.
  14. Brinkworth GD, Luscombe-Marsh ND, Thompson CH, et al. Long-term effects of very low-carbohydrate and high-carbohydrate weight-loss diets on psychological health in obese adults with type 2 diabetes: randomized controlled trial. J Intern Med. 2016;280(4):388-397. doi:10.1111/joim.12501 (with exercise)
  15. Ortega, M.A., Fraile-Martínez, Ó., García-Montero, C., Alvarez-Mon, M.A., Lahera, G., Monserrat, J., Llavero-Valero, M., Mora, F., Rodríguez-Jiménez, R., Fernandez-Rojo, S., Quintero, J., Alvarez De Mon, M., 2022. Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection. Front Nutr 9, 867150. https://doi.org/10.3389/fnut.2022.867150
  16. Gangwisch JE, Hale L, Garcia L, et al. High glycemic index diet as a risk factor for depression: analyses from the Women’s Health Initiative1. Am J Clin Nutr. 2015;102(2):454-463. doi:10.3945/ajcn.114.103846
  17. Cox N, Gibas S, Salisbury M, Gomer J, Gibas K. Ketogenic diets potentially reverse Type II diabetes and ameliorate clinical depression: A case study. Diabetes Metab Syndr. 2019;13(2):1475-1479. doi:10.1016/j.dsx.2019.01.055 ABSTRACT
  18. Geraets AFJ, Köhler S, Muzambi R, et al. The association of hyperglycaemia and insulin resistance with incident depressive symptoms over 4 years of follow-up: The Maastricht Study. Diabetologia. Published online August 5, 2020. doi:10.1007/s00125-020-05247-9
  19. Darooghegi Mofrad M, Siassi F, Guilani B, Bellissimo N, Suitor K, Azadbakht L. The association of food quality index with mental health in women: a cross-sectional study. BMC Res Notes. 2020;13. doi:10.1186/s13104-020-05401-x
  20. Colognesi M, Gabbia D, De Martin S. Depression and Cognitive Impairment—Extrahepatic Manifestations of NAFLD and NASH. Biomedicines. 2020;8(7):229. doi:10.3390/biomedicines8070229
  21. Reis DJ, Ilardi SS, Namekata MS, Wing EK, Fowler CH. The depressogenic potential of added dietary sugars. Medical Hypotheses. 2020;134:109421. doi:10.1016/j.mehy.2019.109421  
  22. LaChance LR, Ramsey D. Antidepressant foods: An evidence-based nutrient profiling system for depression. World J Psychiatry. 2018;8(3):97-104. doi:10.5498/wjp.v8.i3.97
  23. Duygu Sen Z, Vera Danyeli L, Woelfer M, et al. Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: integrating the phenotypic, molecular and neuroanatomical dimensions. Brain, Behavior, and Immunity. Published online December 23, 2020. doi:10.1016/j.bbi.2020.12.020 PDF
  24. Watson KT, Simard JF, Henderson VW, et al. Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study. AJP. Published online September 23, 2021:appi.ajp.2021.20101479. doi:10.1176/appi.ajp.2021.20101479

Anxiety

  1. Daneshzad E, Keshavarz S-A, Qorbani M, Larijani B, Azadbakht L. Association between a low-carbohydrate diet and sleep status, depression, anxiety, and stress score. J Sci Food Agric. 2020;100(7):2946-2952. doi:10.1002/jsfa.10322
  2. Norwitz NG, Naidoo U. Nutrition as Metabolic Treatment for Anxiety. Front Psychiatry. 2021;12:598119. doi:10.3389/fpsyt.2021.598119
  3.  
  4. Włodarczyk A, Cubała WJ, Wielewicka A. Ketogenic Diet: A Dietary Modification as an Anxiolytic Approach? Nutrients. 2020;12(12):3822. doi:10.3390/nu12123822
  5. Bear TLK, Dalziel JE, Coad J, Roy NC, Butts CA, Gopal PK. The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety. Adv Nutr. 2020;11(4):890-907. doi:10.1093/advances/nmaa01
  6. Shegelman A, Carson KA, McDonald TJW, Henry-Barron BJ, Diaz-Arias LA, Cervenka MC. The psychiatric effects of ketogenic diet therapy on adults with chronic epilepsy. Epilepsy & Behavior. 2021;117:107807. doi:10.1016/j.yebeh.2021.107807 ABSTRACT
  7. Kose J, Cheung A, Fezeu LK, et al. A Comparison of Sugar Intake between Individuals with High and Low Trait Anxiety: Results from the NutriNet-Santé Study. Nutrients. 2021;13(5):1526. doi:10.3390/nu13051526
  8. Aucoin, M. et al. (2021) ‘Diet and Anxiety: A Scoping Review’, Nutrients, 13(12), p. 4418. doi:10.3390/nu13124418.

Bipolar Disorder

  1. Campbell IH, Needham N, Grossi H, et al. A Pilot Study of a Ketogenic Diet in Bipolar Disorder: Clinical, Metabolomic and Magnetic Resonance Spectroscopy Outcomes. Published online October 23, 2023:2023.10.23.23297391. doi:10.1101/2023.10.23.23297391    (preprint)
  2. Needham N, Campbell IH, Grossi H, et al. Pilot study of a ketogenic diet in bipolar disorder. BJPsych Open. 2023;9(6):e176. doi:10.1192/bjo.2023.568
  3. H. Campbell I, Campbell H. Ketosis and bipolar disorder: Controlled analytic study of online reports. BJPsych Open. 2019;5. doi:10.1192/bjo.2019.49
  4. Phelps JR, Siemers SV, El-Mallakh RS. The ketogenic diet for type II bipolar disorder. Neurocase. 2013;19(5):423-426. doi:10.1080/13554794.2012.690421 ABSTRACT 
  5. Yu B, Ozveren R, Dalai SS. Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments. doi:10.21203/rs.3.rs-334453/v2
  6. Chmiel I. Ketogenic diet in therapy of bipolar affective disorder – case report and literature review. Psychiatr Pol. 2022;56(6):1345-1363. doi:10.12740/PP/OnlineFirst/136356
  7. Campbell IH, Campbell H, Smith DJ. Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder. Transl Psychiatry. 2022;12(1):1-8. doi:10.1038/s41398-022-02122-6
  8. Calkin C, McClelland C, Cairns K, Kamintsky L, Friedman A. Insulin Resistance and Blood-Brain Barrier Dysfunction Underlie Neuroprogression in Bipolar Disorder. Front Psychiatry. 2021;12. doi:10.3389/fpsyt.2021.636174
  9. Schuster MP, Borkent J, Chrispijn M, et al. Increased prevalence of metabolic syndrome in patients with bipolar disorder compared to a selected control group – A Northern Netherlands LifeLines population cohort study. Journal of Affective Disorders. Published online September 6, 2021. doi:10.1016/j.jad.2021.08.139
  10. Calkin CV. Insulin resistance takes center stage: a new paradigm in the progression of bipolar disorder. Annals of Medicine. 2019;51(5-6):281-293. doi:10.1080/07853890.2019.1659511
  11. Calkin CV, Ruzickova M, Uher R, et al. Insulin resistance and outcome in bipolar disorder. The British Journal of Psychiatry. 2015;206(1):52-57. doi:10.1192/bjp.bp.114.152850
  12. Campbell I, Campbell H. A pyruvate dehydrogenase complex disorder hypothesis for bipolar disorder. Medical Hypotheses. 2019;130:109263. doi:10.1016/j.mehy.2019.109263 (Ketogenic diet, epilepsy and bipolar connections)
  13. 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. Medical Hypotheses. 2020;145:110299. doi:10.1016/j.mehy.2020.110299 ABSTRACT
  14. Mansur RB, Delgado-Peraza F, Subramaniapillai M, et al. Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin. Journal of Psychiatric Research. Published online December 4, 2020. doi:10.1016/j.jpsychires.2020.12.007
  15. Saraga M, Misson N, Cattani E. Ketogenic diet in bipolar disorder. Bipolar Disorders. n/a(n/a). doi:10.1111/bdi.13013 ABSTRACT
  16. Koning, E. et al. (2022) ‘The concept of “metabolic jet lag” in the pathophysiology of bipolar disorder: implications for research and clinical care’, CNS Spectrums, pp. 1–10. Available at: https://doi.org/10.1017/S1092852922001195.
  17. Miola, A. et al. (2023) ‘Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates’, Journal of Affective Disorders, pp. S0165-0327(23)00529–3. Available at: https://doi.org/10.1016/j.jad.2023.04.068.

Schizophrenia

  1. Gilbert-Jaramillo J, Vargas-Pico D, Espinosa-Mendoza T, et al. The effects of the ketogenic diet on psychiatric symptomatology, weight and metabolic dysfunction in schizophrenia patients. Clin Nutr Metab. 2018;1(1). doi:10.15761/CNM.1000105
  2. Kraft BD, Westman EC. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutr Metab (Lond). 2009;6:10. doi:10.1186/1743-7075-6-10
  3. Joseph J, Depp C, Shih PB, Cadenhead KS, Schmid-Schönbein G. Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia? Published online 2017. Front. Neurosci. 11:155. doi: 10.3389/fnins.2017.00155
  4. Adamowicz K, Mazur A, Mak M, Samochowiec J, Kucharska-Mazur J. Metabolic Syndrome and Cognitive Functions in Schizophrenia—Implementation of Dietary Intervention. Front Psychiatry. 2020;11. doi:10.3389/fpsyt.2020.00359
  5. Argüello C. Revisiting Evidence for Recommending a Gluten- Free Diet in Schizophrenia – Review and Presentation. Researchgate/355184985. November 2021.
  6. Levinta A, Mukovozov I, Tsoutsoulas C. Use of a Gluten-Free Diet in Schizophrenia: A Systematic Review. Advances in nutrition (Bethesda, Md). 2018;9. doi:10.1093/advances/nmy056 ABSTRACT
  7. Jackson J, Eaton W, Cascella N, et al. A gluten-free diet in people with schizophrenia and anti-tissue transglutaminase or anti-gliadin antibodies. Schizophrenia research. 2012;140:262-263. doi:10.1016/j.schres.2012.06.011
  8. Rubin A. Gluten-Free Intervention for Schizophrenia. American Journal of Psychiatry Residents’ Journal. 2020;15(3):8-8. (Commentary) doi:10.1176/appi.ajp-rj.2020.150303
  9. Nandeesha H, Keshri N, Rajappa M, Menon V. Association of hyperglycaemia and hyperlipidaemia with cognitive dysfunction in schizophrenia spectrum disorder. Arch Physiol Biochem. Published online November 3, 2020:1-8. doi:10.1080/13813455.2020.1839500 ABSTRACT
  10. Wijtenburg SA, Kapogiannis D, Korenic S, et al. Brain Insulin Resistance and Altered Brain Glucose are Related to Memory Impairments in Schizophrenia. Schizophr Res. 2019;208:324-330. doi:10.1016/j.schres.2019.01.031 PDF
  11. Sarnyai Z, Kraeuter A-K, Palmer CM. Ketogenic diet for schizophrenia: clinical implication. Curr Opin Psychiatry. June 2019. doi:10.1097/YCO.0000000000000535 ABSTRACT  
  12. Włodarczyk A, Wiglusz MS, Cubała WJ. Ketogenic diet for schizophrenia: Nutritional approach to antipsychotic treatment. Medical Hypotheses. 2018;118:74-77. doi:10.1016/j.mehy.2018.06.022 ABSTRACT
  13. Palmer CM, Gilbert-Jaramillo J, Westman EC. The ketogenic diet and remission of psychotic symptoms in schizophrenia: Two case studies. Schizophr Res. April 2019. doi:10.1016/j.schres.2019.03.019 NO ABSTRACT
  14. Palmer CM. Ketogenic diet in the treatment of schizoaffective disorder: Two case studies. Schizophrenia Research. 2017;189:208-209. doi:10.1016/j.schres.2017.01.053 NO ABSTRACT
  15. Hu J, Zhou Y, Wang R, et al. Abnormal glucose metabolism is associated with clinical symptoms of adolescent-onset patients with first-episode drug-naive schizophrenia. Asian J Psychiatr. 2021;62:102716. doi:10.1016/j.ajp.2021.102716 ABSTRACT

Anorexia Nervosa and Obsessive Compulsive Disorder

To be considered with caution. These disorders have been listed together due to the fact they are highly co-morbid which may be an important consideration for treatment. See media links for examples of clinicians using a reduced carbohydrate approach for disordered eating.

  1. Calabrese, L., Scolnick, B., Zupec-Kania, B., Beckwith, C., Costello, K., Frank, G.K.W., 2022. Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study. Eat Weight Disord. doi.org/10.1007/s40519-022-01455-x
  2. Norwitz, N.G., Hurn, M. and Forcen, F.E. (2023) ‘Animal-based ketogenic diet puts severe anorexia nervosa into multi-year remission: A case series’, Journal of Insulin Resistance, 6(1), p. 8. Available at: https://insulinresistance.org/index.php/jir/article/view/84.
  3. Scolnick, B. and Beckwith, C. (2023) ‘Synergy between ketamine and ketogenic diet in anorexia nervosa, and other neurobehavioral disorders’, Eating and Weight Disorders, 28(1), p. 8. Available at: https://doi.org/10.1007/s40519-023-01528-5.
  4. Scolnick B, Zupec-Kania B, Calabrese L, Aoki C, Hildebrandt T. Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report. Front Psychiatry. 2020;11. doi:10.3389/fpsyt.2020.00763
  5. Buck, P. et al. (2022) ‘Carbohydrate malabsorption in anorexia nervosa: a systematic review’, Journal of Eating Disorders, 10(1), p. 189. Available at: https://doi.org/10.1186/s40337-022-00713-8.
  6. Rodrigo L, Álvarez N, Fernández-Bustillo E, Salas-Puig J, Huerta M, Hernández-Lahoz C. Efficacy of a Gluten-Free Diet in the Gilles de la Tourette Syndrome: A Pilot Study. Nutrients. 2018;10(5). doi:10.3390/nu10050573
  7. Holton KF, Cotter EW. Could dietary glutamate be contributing to the symptoms of obsessive-compulsive disorder? Future Sci OA. 2018;4(3). doi:10.4155/fsoa-2017-0105
  8. Couture DC, Chung MK, Shinnick P, Curzon J, McClure MJ, LaRiccia PJ. Integrative Medicine Approach to Pediatric Obsessive-Compulsive Disorder and Anxiety: A Case Report. Glob Adv Health Med. 2016;5(1):117-121. doi:10.7453/gahmj.2015.091
  9. Seitz J, Dahmen B, Keller L, Herpertz-Dahlmann B. Gut Feelings: How Microbiota Might Impact the Development and Course of Anorexia Nervosa. Nutrients. 2020;12(11):3295. doi:10.3390/nu12113295
  10. Parker, E.K. et al. (2021) ‘A standard enteral formula versus an iso-caloric lower carbohydrate/high fat enteral formula in the hospital management of adolescent and young adults admitted with anorexia nervosa: a randomised controlled trial’, Journal of Eating Disorders, 9(1), p. 160. doi:10.1186/s40337-021-00513-6.
  11. Scolnick B. Ketogenic diet and anorexia nervosa. Medical Hypotheses. 2017;109:150-152. doi:10.1016/j.mehy.2017.10.011 ABSTRACT
 

PTSD and Glutamate

  1. Brandley E, Kirkland A, Sarlo G, VanMeter J, Baraniuk J, Holton K. The Effects of a Low Glutamate Dietary Intervention on Anxiety and PTSD in Veterans with Gulf War Illness (FS15-08-19). Curr Dev Nutr. 2019;3(Supplement_1). doi:10.1093/cdn/nzz031.FS15-08-19
  2. Brandley E, Kirkland A, Holton K. Gulf War Veterans with Psychiatric Symptoms (Anxiety, Depression, and PTSD) Significantly Improve on a Low Glutamate Diet. Curr Dev Nutr. 2020;4(Supplement_2):1192-1192. doi:10.1093/cdn/nzaa057_008
  3. Kraal AZ, Arvanitis NR, Jaeger AP, Ellingrod VL. Could Dietary Glutamate Play a Role in Psychiatric Distress? NPS. 2020;79(1-2):13-19. doi:10.1159/000496294
  4. Li C-T, Yang K-C, Lin W-C. Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies. Front Psychiatry. 2019;9. doi:10.3389/fpsyt.2018.00767

Substance Use Disorders

 
  1. Kong, D. et al. (2023) ‘Ketogenic diet: a potential adjunctive treatment for substance use disorders’, Frontiers in Nutrition, 10. Available at: https://www.frontiersin.org/articles/10.3389/fnut.2023.1191903.
  2. Mahajan, V.R. et al. (2021) ‘Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder’, Frontiers in Psychiatry, 12. doi:10.3389/fpsyt.2021.781668.
  3. Wiers, C.E. et al. (2023) ‘Ketogenic diet reduces a neurobiological craving signature in alcohol use disorder’, medRxiv, p. 2023.09.25.23296094. Available at: https://doi.org/10.1101/2023.09.25.23296094.
  4. Wiers, C.E. et al. (2021) ‘Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents’, Science Advances, 7(15), p. eabf6780. doi:10.1126/sciadv.abf6780.
  5. Jia, D. and Xu, Y. (2022) ‘Effects of an 8-week Baduanjin intervention combined with low-carbohydrates diet among overweight people who struggle with drug addiction’, Frontiers in Public Health, 10, p. 989519. Available at: https://doi.org/10.3389/fpubh.2022.989519.
  6. Li, X. et al. (2023) ‘Pharmacokinetic effects of a single-dose nutritional ketone ester supplement on brain ketone and glucose metabolism in alcohol use disorder – a pilot study’, medRxiv, p. 2023.09.25.23296090. Available at: https://doi.org/10.1101/2023.09.25.23296090.
  7. Li, X. et al. (2022) ‘Brain glutamate and sleep efficiency associations following a ketogenic diet intervention in individuals with Alcohol Use Disorder’, Drug and Alcohol Dependence Reports, p. 100092. Available at: https://doi.org/10.1016/j.dadr.2022.100092.
  8. Li, X. et al. (2023) ‘Ketone supplementation dampens subjective and objective responses to alcohol in rats and humans’, bioRxiv, p. 2023.09.23.558269. Available at: https://doi.org/10.1101/2023.09.23.558269.
  9. The Ketogenic Diet and Alcohol: Withdrawal, Hangover, Cravings, and Consumption – ProQuest  28542923 (2021). 
  10. Castro AI, Gomez-Arbelaez D, Crujeiras AB, et al. Effect of A Very Low-Calorie Ketogenic Diet on Food and Alcohol Cravings, Physical and Sexual Activity, Sleep Disturbances, and Quality of Life in Obese Patients. Nutrients. 2018;10(10). doi:10.3390/nu10101348
  11. Wiss, D.A. (2019) ‘Chapter 2 – The Role of Nutrition in Addiction Recovery: What We Know and What We Don’t’, in Danovitch, I. and Mooney, L.J. (eds) The Assessment and Treatment of Addiction. Elsevier, pp. 21–42. doi:10.1016/B978-0-323-54856-4.00002-X. ABSTRACT
  12. Mizuo, K. Diet, Nutrition, and Opioid Addiction | Abstract (2021). Journal of Alcoholism & Drug Dependence ISSN: 2329-6488. ABSTRACT
  13. Mbugua, S. et al. (2021) ‘Association between Metabolic Syndrome and Substance Dependence: A Cross-sectional Study in Kenya’. doi:10.21203/rs.3.rs-139422/v1.

Pre-clinical and Ongoing Trials

  1. Ketone Ester Intervention in Alcohol Use Disorder – Full Text View – ClinicalTrials.gov (2020). Identifier: NCT04616781 – Ongoing clinical trial 
  2. Blanco-Gandía, M. del C. et al. (2021) ‘Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice’, Nutrients, 13(7), p. 2167. doi:10.3390/nu13072167.
  3. Bornebusch, A.B. et al. (2021) ‘Effects of ketogenic diet and ketone monoester supplement on acute alcohol withdrawal symptoms in male mice’, Psychopharmacology. doi:10.1007/s00213-020-05735-1.

Medication - Cautions and Metabolic Changes/Weight Gain

Due to the therapeutic effect of carbohydrate restriction, medical supervision is advised when adopting this approach – reflected in the following article: Ede G (Author), Scher B (Medical review) Low Carb and Mental Health: Getting Started & Managing Medications. Diet Doctor.

The following section highlights the potential of medications to cause metabolic syndrome and weight gain. The therapeutic application of carbohydrate restriction may also have a role in this setting.

  1. Alonso-Pedrero L, Bes-Rastrollo M, Marti A. Effects of antidepressant and antipsychotic use on weight gain: A systematic review. Obes Rev. 2019;20(12):1680-1690. doi:10.1111/obr.12934 ABSTRACT
  2. Cao H, Meng Y, Li X, et al. The metabolic effects of antipsychotics in the early stage of treatment in first-episode patients with schizophrenia: A real-world study in a naturalistic setting. Journal of Psychiatric Research. 2020;129:265-271. doi:10.1016/j.jpsychires.2020.07.038 ABSTRACT
  3. Gurusamy J, Gandhi S, Damodharan D, Ganesan V, Palaniappan M. Exercise, diet and educational interventions for metabolic syndrome in persons with schizophrenia: A systematic review. Asian J Psychiatr. 2018;36:73-85. doi:10.1016/j.ajp.2018.06.018
  4. Bradshaw T, Mairs H. Obesity and Serious Mental Ill Health: A Critical Review of the Literature. Healthcare. 2014;2(2):166-182. doi:10.3390/healthcare2020166
  5. Abo Alrob O, Alazzam S, Alzoubi K, et al. The Effect of Long-Term Second-Generation Antipsychotics Use on the Metabolic Syndrome Parameters in Jordanian Population. Medicina (Kaunas). 2019;55(7). doi:10.3390/medicina55070320
  6. Carli M, Kolachalam S, Longoni B, et al. Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences. Pharmaceuticals. 2021;14(3):238. doi:10.3390/ph14030238
  7. Faulkner G, Soundy AA, Lloyd K. Schizophrenia and weight management: a systematic review of interventions to control weight. Acta Psychiatrica Scandinavica. 2003;108(5):324-332. doi:10.1034/j.1600-0447.2003.00218.x  PDF
  8. Asmar KE, Fève B, Colle R, et al. Early weight gain predicts later weight gain in depressed patients treated with antidepressants: Findings from the METADAP cohort. J Affect Disord. 2018;241:22-28. doi:10.1016/j.jad.2018.07.059
  9. Jaberi N, Faramarzi E, Farahbakhsh M, Ostadarahimi A, Asghari Jafarabadi M, Fakhari A. Prevalence of metabolic syndrome in schizophrenia patients treated with antipsychotic medications. Caspian J Intern Med. 2020;11(3):310-314. doi:10.22088/cjim.11.3.310
  10. Bussell K, Reeves G, Hager E, et al. Dietary Consumption Among Youth with Antipsychotic-Induced Weight Gain and Changes Following Healthy Lifestyle Education. J Child Adolesc Psychopharmacol. 2021;31(5):364-375. doi:10.1089/cap.2020.0173 ABSTRACT
  11. Khasanova, A.K., Dobrodeeva, V.S., Shnayder, N.A., Petrova, M.M., Pronina, E.A., Bochanova, E.N., Lareva, N.V., Garganeeva, N.P., Smirnova, D.A., Nasyrova, R.F., 2022. Blood and Urinary Biomarkers of Antipsychotic-Induced Metabolic Syndrome. Metabolites 12, 726. doi.org/10.3390/metabo12080726

Food Addiction and Binge Eating Disorder Spectrum

Food Addiction is an emerging and complicated area of interest that may be part of the clinical picture for some patients. The following papers reflect the main points of discussion and support the concept that food addiction may be a ‘valid phenotype of obesity’ and ‘should be incorporated into the spectrum of disordered eating’.

Studies
  1. Unwin, J. et al. (2022) ‘Low carbohydrate and psychoeducational programs show promise for the treatment of ultra-processed food addiction’, Frontiers in Psychiatry, 13. Available at: https://www.frontiersin.org/articles/10.3389/fpsyt.2022.1005523.
  2. Anguah KO-B, Syed-Abdul MM, Hu Q, et al. Changes in Food Cravings and Eating Behavior after a Dietary Carbohydrate Restriction Intervention Trial. Nutrients. 2020;12(1):52. doi:10.3390/nu12010052
  3. Carmen M, Safer DL, Saslow LR, et al. Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series. J Eat Disord. 2020;8(1):2. doi:10.1186/s40337-020-0278-7
  4. Castro AI, Gomez-Arbelaez D, Crujeiras AB, et al. Effect of A Very Low-Calorie Ketogenic Diet on Food and Alcohol Cravings, Physical and Sexual Activity, Sleep Disturbances, and Quality of Life in Obese Patients. Nutrients. 2018;10(10). doi:10.3390/nu10101348
  5. Sethi Dalai S, Sinha A, Gearhardt AN. Low carbohydrate ketogenic therapy as a metabolic treatment for binge eating and ultraprocessed food addiction. Current Opinion in Endocrinology, Diabetes and Obesity. 2020;27(5):275–282. doi:10.1097/MED.0000000000000571 ABSTRACT
  6. Ayton A, Ibrahim A, Dugan J, Galvin E, Wroe-Wright O. Ultra-Processed Foods and Binge Eating: A Retrospective Observational Study. NutriXiv; 2020. doi:10.31232/osf.io/3gdtw
  7. Rostanzo, E. et al. (2021) ‘Very-Low-Calorie Ketogenic Diet: A Potential Treatment for Binge Eating and Food Addiction Symptoms in Women. A Pilot Study’, International Journal of Environmental Research and Public Health, 18(23), p. 12802. Available at: https://doi.org/10.3390/ijerph182312802.
  8. Černelič-Bizjak, M. et al. (2023) ‘Link between emotional and external eating behaviors, peripheral neuropeptide Y, and β-hydroxybutyrate in participants with obesity on 12-week ketogenic diet’, Nutrition and Health, p. 026010602311544. Available at: https://doi.org/10.1177/02601060231154464.
  9. Gearhardt AN, White MA, Masheb RM, Morgan PT, Crosby RD, Grilo CM. An Examination of the Food Addiction Construct in Obese Patients with Binge Eating Disorder. Int J Eat Disord. 2012;45(5):657-663. doi:10.1002/eat.20957
  10. Gearhardt AN, White MA, Masheb RM, Grilo CM. An Examination of Food Addiction in a Racially Diverse Sample of Obese Patients with Binge Eating Disorder in Primary Care Settings. Compr Psychiatry. 2013;54(5):500-505. doi:10.1016/j.comppsych.2012.12.009
  11. Imperatori C, Innamorati M, Lamis DA, et al. Childhood trauma in obese and overweight women with food addiction and clinical-level of binge eating. Child Abuse Negl. 2016;58:180-190. doi:10.1016/j.chiabu.2016.06.023
  12. Aviram-Friedman R, Kafri L, Baz G, Alyagon U, Zangen A. Prisoners of Addictive Cues: Biobehavioral Markers of Overweight and Obese Adults with Food Addiction. Nutrients. 2020;12(11):3563. doi:10.3390/nu12113563
  13. Darcey, V.L. et al. (2022) Restriction of dietary fat, but not carbohydrate, alters brain reward circuitry in adults with obesity. preprint. Neuroscience. doi:10.1101/2022.04.19.488800.
  14. de Oliveira, J. et al. (2023) ‘Very low-calorie ketogenic diet in the treatment of adaptive thermogenesis: A case report’, Nutrition (Burbank, Los Angeles County, Calif.), 117, p. 112252. Available at: https://doi.org/10.1016/j.nut.2023.112252.
 
Reviews
  1. Sethi Dalai, S., Sinha, A. and Gearhardt, A.N. (2020) ‘Low carbohydrate ketogenic therapy as a metabolic treatment for binge eating and ultraprocessed food addiction’, Current Opinion in Endocrinology, Diabetes, and Obesity, 27(5), pp. 275–282. Available at: https://doi.org/10.1097/MED.0000000000000571.
  2. Gordon EL, Ariel-Donges AH, Bauman V, Merlo LJ. What Is the Evidence for “Food Addiction?” A Systematic Review. Nutrients. 2018;10(4). doi:10.3390/nu10040477
  3. Gearhardt, A.N. and DiFeliceantonio, A.G. (no date) ‘Highly processed foods can be considered addictive substances based on established scientific criteria’, Addiction, n/a(n/a). Available at: https://doi.org/10.1111/add.16065.
  4. Constant A, Moirand R, Thibault R, Val-Laillet D. Meeting of Minds around Food Addiction: Insights from Addiction Medicine, Nutrition, Psychology, and Neurosciences. Nutrients. 2020;12(11):3564. doi:10.3390/nu12113564
  5. Wiss D, Brewerton T. Separating the Signal from the Noise: How Psychiatric Diagnoses Can Help Discern Food Addiction from Dietary Restraint. Nutrients. 2020;12(10). doi:10.3390/nu12102937
  6. Grigolon RB, Gerchman F, Schöffel AC, et al. Mental, emotional, and behavioral effects of ketogenic diet for non-epileptic neuropsychiatric conditions. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2020;102:109947. doi:10.1016/j.pnpbp.2020.109947 ABSTRACT
  7. Ayton A, Ibrahim A. The Western diet: a blind spot of eating disorder research?—a narrative review and recommendations for treatment and research. Nutr Rev. 2020;78(7):579-596. doi:10.1093/nutrit/nuz089
  8. Adams RC, Sedgmond J, Maizey L, Chambers CD, Lawrence NS. Food Addiction: Implications for the Diagnosis and Treatment of Overeating. Nutrients. 2019;11(9):2086. doi:10.3390/nu11092086
  9. Hauck C, Cook B, Ellrott T. Food addiction, eating addiction and eating disorders. Proc Nutr Soc. 2020;79(1):103-112. doi:10.1017/S0029665119001162
  10. Wiss DA, Avena N, Gold M. Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications. Nutrients. 2020;12(11):3521. doi:10.3390/nu12113521
  11. Gearhardt AN, Hebebrand J. The concept of “food addiction” helps inform the understanding of overeating and obesity: YES. The American Journal of Clinical Nutrition. 2021;113(2):263-267. doi:10.1093/ajcn/nqaa343 . See these links for NO & DEBATE CONSENSUS
Media Links
  1. Low Carb MD Podcast – Episode 69: Dr. Molly Rutherford. Google Podcasts
  2. Fast Keto with Ketogenic Girl – Beating Sugar Addiction with Dr Jen Unwin & Bitten Jonsson. Google Podcasts (from 4m30s)
  3. Low Carb MD Podcast – Episode 162. Google Podcasts. Dr. Ali Ibrahim – consultant child and adolescent eating disorders psychiatrist
  4. Public Health Collaboration. Is What We Eat Relevant to Eating Disorders? By Dr Agnes Ayton & Dr Ali Ibrahim  #PHCvcon2021. 

Appetite Control

  1. Gibson AA, Seimon RV, Lee CMY, et al. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obesity Reviews. 2015;16(1):64-76. doi:10.1111/obr.12230 PDF
  2. Hu T, Yao L, Reynolds K, et al. The Effects of a Low-Carbohydrate Diet on Appetite: A Randomized Controlled Trial. Nutr Metab Cardiovasc Dis. 2016;26(6):476-488. doi:10.1016/j.numecd.2015.11.011
  3. Johnstone AM, Horgan GW, Murison SD, Bremner DM, Lobley GE. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am J Clin Nutr. 2008;87(1):44-55. doi:10.1093/ajcn/87.1.44
  4. Stubbs, B.J. et al. (2018) ‘A Ketone Ester Drink Lowers Human Ghrelin and Appetite’, Obesity (Silver Spring, Md.), 26(2), p. 269. doi:10.1002/oby.22051.
  5. Vestergaard ET, Zubanovic NB, Rittig N, et al. Acute ketosis inhibits appetite and decreases plasma concentrations of acyl ghrelin in healthy humans. Diabetes Obes Metab. Published online April 14, 2021. doi:10.1111/dom.14402
  6. Martins C, Nymo S, Truby H, Rehfeld JF, Hunter GR, Gower BA. Association Between Ketosis and Changes in Appetite Markers with Weight Loss Following a Very Low-Energy Diet. Obesity. 2020;28(12):2331-2338. doi:10.1002/oby.23011
  7. Holsen LM, Hoge WS, Lennerz BS, et al. Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults. The Journal of Nutrition. 2021;(nxab090). doi:10.1093/jn/nxab090
  8. Sumithran P, Prendergast LA, Delbridge E, et al. Ketosis and appetite-mediating nutrients and hormones after weight loss. European Journal of Clinical Nutrition. 2013;67(7):759-764. doi:10.1038/ejcn.2013.90
  9. Paoli A, Bosco G, Camporesi EM, Mangar D. Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol. 2015;6. doi:10.3389/fpsyg.2015.00027 
  10. Wyatt P, Berry SE, Finlayson G, et al. Postprandial glycaemic dips predict appetite and energy intake in healthy individuals. Nature Metabolism. Published online April 12, 2021:1-7. doi:10.1038/s42255-021-00383-x 
  11. Roekenes J, Martins C. Ketogenic diets and appetite regulation. Current Opinion in Clinical Nutrition & Metabolic Care. 2021;Publish Ahead of Print. doi:10.1097/MCO.0000000000000760
  12. B Keogh J, M Clifton P. Energy Intake and Satiety Responses of Eggs for Breakfast in Overweight and Obese Adults—A Crossover Study. Int J Environ Res Public Health. 2020;17(15). doi:10.3390/ijerph17155583
  13. ao Y, Tsintzas K, Macdonald IA, Cordon SM, Taylor MA. Effects of intermittent (5:2) or continuous energy restriction on basal and postprandial metabolism: a randomised study in normal-weight, young participants. European Journal of Clinical Nutrition. Published online May 26, 2021:1-9. doi:10.1038/s41430-021-00909-2 (appetite considered)
  14. Darcey, V.L. et al. (2022) Restriction of dietary fat, but not carbohydrate, alters brain reward circuitry in adults with obesity. preprint. Neuroscience. doi:10.1101/2022.04.19.488800.
  15. Rondanelli M, Perna S, Ilyas Z, et al. Effect of very low-calorie ketogenic diet in combination with omega-3 on inflammation, satiety hormones, body composition, and metabolic markers. A pilot study in class I obese subjects. Endocrine. Published online September 16, 2021. doi:10.1007/s12020-021-02860-5

For additional articles on appetite suppression see Time Restricted Feeding