Intranasal oxytocin as a treatment for obesity: safety and efficacy

INTRODUCTION Known for its effect on labor and lactation and on emotional and social functions, oxytocin has recently emerged as a key modulator of feeding behavior and indeed suggested as a potential treatment for obesity. The potential positive effect of oxytocin on both metabolic and psychological-behavioral complications of hypothalamic lesions makes it a promising tool in the management of these conditions. AREAS COVERED The aim of the present review article is to provide an overview of the mechanism of action and clinical experience of the use of oxytocin in different forms of obesity. EXPERT OPINION Current evidence suggests a potential role of oxytocin in the treatment of obesity with different causes. Several challenges remain: an improved understanding of the physiological regulation, mechanisms of action of oxytocin, and interplay with other endocrine axes is fundamental to clarify its role. Further clinical trials are needed to determine the safety and efficacy of oxytocin for the treatment of different forms of obesity. Understanding the mechanism(s) of action of oxytocin on body weight regulation might also improve our understanding of obesity and reveal possible new therapeutic targets - as well as promoting advances in other fields in which oxytocin might be used.

[1]  M. Coupaye,et al.  Bone Health in Adults With Prader–Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study , 2022, The Journal of clinical endocrinology and metabolism.

[2]  N. Kataoka,et al.  An oxytocinergic neural pathway that stimulates thermogenic and cardiac sympathetic outflow. , 2022, Cell reports.

[3]  V. Grinevich,et al.  Oxytocin-based therapies for treatment of Prader-Willi and Schaaf-Yang syndromes: evidence, disappointments, and future research strategies , 2022, Translational Psychiatry.

[4]  A. J. van der Lely,et al.  Health Problems in Adults with Prader–Willi Syndrome of Different Genetic Subtypes: Cohort Study, Meta-Analysis and Review of the Literature , 2022, Journal of clinical medicine.

[5]  V. Burmester,et al.  Intranasal oxytocin reduces attentional bias to food stimuli , 2021, Appetite.

[6]  E. Loh,et al.  Effects of intranasal oxytocin in food intake and craving: A meta-analysis of clinical trials. , 2021, Clinical nutrition.

[7]  E. Lawson,et al.  The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans , 2021, International journal of molecular sciences.

[8]  C. Camerino Oxytocin Involvement in Body Composition Unveils the True Identity of Oxytocin , 2021, International journal of molecular sciences.

[9]  S. Espinoza,et al.  Intranasal Oxytocin Improves Lean Muscle Mass and Lowers LDL Cholesterol in Older Adults with Sarcopenic Obesity: Aa Pilot Randomized Controlled Trial. , 2021, Journal of the American Medical Directors Association.

[10]  Jillian M. Rung,et al.  Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial , 2021, Psychopharmacology.

[11]  F. Faggiano,et al.  Obesity in Prader–Willi syndrome: physiopathological mechanisms, nutritional and pharmacological approaches , 2021, Journal of Endocrinological Investigation.

[12]  H. Lane,et al.  Oxytocin in Schizophrenia: Pathophysiology and Implications for Future Treatment , 2021, International journal of molecular sciences.

[13]  J. Visser,et al.  Oxytocin in young children with Prader‐Willi syndrome: Results of a randomized, double‐blind, placebo‐controlled, crossover trial investigating 3 months of oxytocin , 2020, Clinical endocrinology.

[14]  F. Plessow,et al.  Oxytocin Administration Increases Proactive Control in Men with Overweight or Obesity: A Randomized, Double‐Blind, Placebo‐Controlled Crossover Study , 2020, Obesity.

[15]  E. Hollander,et al.  Intranasal oxytocin versus placebo for hyperphagia and repetitive behaviors in children with Prader-Willi Syndrome: A randomized controlled pilot trial. , 2020, Journal of psychiatric research.

[16]  A. Marsh,et al.  Oxytocin and the Neurobiology of Prosocial Behavior , 2020, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[17]  D. Quintana,et al.  Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research , 2020, Molecular Psychiatry.

[18]  H. Müller Management of Hypothalamic Obesity. , 2020, Endocrinology and metabolism clinics of North America.

[19]  C. Thiel,et al.  Social Cognition in Patients With Hypothalamic-Pituitary Tumors , 2020, Frontiers in Oncology.

[20]  Jianhong Wu,et al.  The global burden of disease attributable to high body mass index in 195 countries and territories, 1990–2017: An analysis of the Global Burden of Disease Study , 2020, PLoS medicine.

[21]  L. Schilbach,et al.  Oxytocin release deficit and social cognition in craniopharyngioma patients , 2020, Journal of neuroendocrinology.

[22]  E. Lawson,et al.  Metabolic Effects of Oxytocin. , 2019, Endocrine reviews.

[23]  T. Merchant,et al.  Craniopharyngioma , 2019, Nature Reviews Disease Primers.

[24]  M. Butler,et al.  Prader-Willi Syndrome - Clinical Genetics, Diagnosis and Treatment Approaches: An Update , 2019, Current pediatric reviews.

[25]  T. Onaka,et al.  Role of oxytocin in the control of stress and food intake , 2019, Journal of neuroendocrinology.

[26]  D. Penn,et al.  Effects of oxytocin on empathy, introspective accuracy, and social symptoms in schizophrenia: A 12-week twice-daily randomized controlled trial , 2019, Schizophrenia Research.

[27]  A. Rees,et al.  Oxytocin therapy in hypopituitarism: Challenges and opportunities , 2018, Clinical endocrinology.

[28]  C. Cobelli,et al.  Intranasal oxytocin fails to acutely improve glucose metabolism in obese men , 2018, Diabetes, obesity & metabolism.

[29]  M. Leow,et al.  Oxytocin in metabolic homeostasis: implications for obesity and diabetes management , 2018, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[30]  R. Adan,et al.  Pathophysiology and Individualized Treatment of Hypothalamic Obesity Following Craniopharyngioma and Other Suprasellar Tumors: A Systematic Review. , 2018, Endocrine reviews.

[31]  F. Hu,et al.  The Science of Obesity Management: An Endocrine Society Scientific Statement. , 2018, Endocrine reviews.

[32]  Lei Feng,et al.  Systematic review and meta‐analysis of reported adverse events of long‐term intranasal oxytocin treatment for autism spectrum disorder , 2018, Psychiatry and clinical neurosciences.

[33]  H. Preissl,et al.  Oxytocin curbs calorie intake via food-specific increases in the activity of brain areas that process reward and establish cognitive control , 2018, Scientific Reports.

[34]  C. Roth,et al.  Oxytocin and Naltrexone Successfully Treat Hypothalamic Obesity in a Boy Post-Craniopharyngioma Resection , 2018, The Journal of clinical endocrinology and metabolism.

[35]  J. Schopohl,et al.  De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function , 2018, Psychoneuroendocrinology.

[36]  Tara M. Holmes,et al.  Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men , 2018, Neuropsychopharmacology.

[37]  L. Heisler,et al.  An appetite for life: brain regulation of hunger and satiety , 2017, Current opinion in pharmacology.

[38]  E. Lawson The effects of oxytocin on eating behaviour and metabolism in humans , 2017, Nature Reviews Endocrinology.

[39]  Jacqueline L Johnson,et al.  A 12-week randomized controlled trial of twice-daily intranasal oxytocin for social cognitive deficits in people with schizophrenia , 2017, Schizophrenia Research.

[40]  P. Fletcher,et al.  Oxytocin administration suppresses hypothalamic activation in response to visual food cues , 2017, Scientific Reports.

[41]  A. Manstead,et al.  Hypopituitarism is associated with lower oxytocin concentrations and reduced empathic ability , 2017, Endocrine.

[42]  D. Johnston,et al.  The effectiveness of interventions to treat hypothalamic obesity in survivors of childhood brain tumours: a systematic review , 2017, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[43]  D. J. Driscoll,et al.  Oxytocin treatment in children with Prader–Willi syndrome: A double‐blind, placebo‐controlled, crossover study , 2017, American journal of medical genetics. Part A.

[44]  H. Müller Risk-adapted, long-term management in childhood-onset craniopharyngioma , 2017, Pituitary.

[45]  C. Thiel,et al.  First experiences with neuropsychological effects of oxytocin administration in childhood-onset craniopharyngioma , 2017, Endocrine.

[46]  K. Boulanouar,et al.  The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader–Willi Syndrome , 2017, Pediatrics.

[47]  A. Hokken-Koelega,et al.  Promising effects of oxytocin on social and food‐related behaviour in young children with Prader–Willi syndrome: a randomized, double‐blind, controlled crossover trial , 2016, Clinical endocrinology.

[48]  Poppy Siddell,et al.  Interventions for managing weight change following paediatric acquired brain injury: a systematic review , 2016, Developmental medicine and child neurology.

[49]  C. Thiel,et al.  Oxytocin in survivors of childhood-onset craniopharyngioma , 2016, Endocrine.

[50]  C. Cobelli,et al.  Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men , 2016, Diabetes.

[51]  Jennifer L Miller,et al.  Parent observed neuro-behavioral and pro-social improvements with oxytocin following surgical resection of craniopharyngioma , 2016, Journal of pediatric endocrinology & metabolism : JPEM.

[52]  W. Maier,et al.  Oxytocin enhances cognitive control of food craving in women , 2016, Human brain mapping.

[53]  Lars T. Westlye,et al.  Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial , 2016, Psychoneuroendocrinology.

[54]  Vishwanath T. Anekonda,et al.  Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization. , 2016, American journal of physiology. Regulatory, integrative and comparative physiology.

[55]  L. Zwaigenbaum,et al.  Autism spectrum disorder in Prader–Willi syndrome: A systematic review , 2015, American journal of medical genetics. Part A.

[56]  O. Andreassen,et al.  Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment , 2015, Translational Psychiatry.

[57]  A. Bereket,et al.  Hypothalamic obesity in children: pathophysiology to clinical management , 2015, Journal of pediatric endocrinology & metabolism : JPEM.

[58]  M. Schwartz,et al.  Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys. , 2015, American journal of physiology. Regulatory, integrative and comparative physiology.

[59]  Tara M. Holmes,et al.  Oxytocin reduces caloric intake in men , 2015, Obesity.

[60]  Y. Ueta,et al.  Oxytocinergic circuit from paraventricular and supraoptic nuclei to arcuate POMC neurons in hypothalamus , 2014, FEBS letters.

[61]  A. Guastella,et al.  A double‐blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome , 2014, American journal of medical genetics. Part A.

[62]  J. Altirriba,et al.  Divergent effects of oxytocin treatment of obese diabetic mice on adiposity and diabetes. , 2014, Endocrinology.

[63]  J. Born,et al.  Oxytocin Reduces Reward-Driven Food Intake in Humans , 2013, Diabetes.

[64]  D. Cai,et al.  Treatment of Obesity and Diabetes Using Oxytocin or Analogs in Patients and Mouse Models , 2013, PloS one.

[65]  G. Elena,et al.  Prader-Willi Syndrome: Clinical Aspects , 2012, Journal of obesity.

[66]  E. Aylward,et al.  Functional Neuroimaging in Craniopharyngioma: A Useful Tool to Better Understand Hypothalamic Obesity? , 2012, Obesity Facts.

[67]  T. Yada,et al.  Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass , 2011, Aging.

[68]  W. Wahli,et al.  Mechanisms of the Anti-Obesity Effects of Oxytocin in Diet-Induced Obese Rats , 2011, PloS one.

[69]  Florence Levy,et al.  A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research , 2011, Psychoneuroendocrinology.

[70]  C. Mantoulan,et al.  Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients , 2011, Orphanet journal of rare diseases.

[71]  D. C. Driscoll,et al.  Nutritional phases in Prader–Willi syndrome , 2011, American journal of medical genetics. Part A.

[72]  A. Zallone,et al.  Oxytocin is an anabolic bone hormone , 2009, Proceedings of the National Academy of Sciences.

[73]  Paulus S. Wang,et al.  Involvement of cholecystokinin receptor in the inhibition of gastrointestinal motility by oxytocin in ovariectomized rats. , 2008, European journal of pharmacology.

[74]  T. Kawada,et al.  Impaired Thermoregulatory Ability of Oxytocin-Deficient Mice during Cold-Exposure , 2007, Bioscience, biotechnology, and biochemistry.

[75]  U. Fischbacher,et al.  Oxytocin increases trust in humans , 2005, Nature.

[76]  L. Rinaman,et al.  GLP-1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[77]  S. Schwartz,et al.  The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. , 2001, Pediatrics.

[78]  C. McDougle,et al.  The role of central oxytocin in obsessive compulsive disorder and related normal behavior , 1994, Psychoneuroendocrinology.

[79]  S. Akhondzadeh,et al.  Intranasal Oxytocin as an Adjunct to Risperidone in Patients with Schizophrenia , 2012, CNS Drugs.