Shebani Sethi MD, ABOM

All Publications

• Impact of a ketogenic diet on metabolic and psychiatric health in patients with bipolar or schizophrenia illness: A pilot clinical trial Sethi, S., Saslow, L., Ketter, T. WILEY. 2023: 19-20

  View details for Web of Science ID 001057367400035

• The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review Journal of Psychiatry & Brain Sciences Sethi , S., Ford , J. 2022; 7:e220009.

  View details for DOI 10.20900/jpbs.20220009

• Treating Binge Eating and Food Addiction Symptoms with Low-carbohydrate Ketogenic Diets: A Case Series Carmen , M., Safer, D. L., Saslow, L. R., Kalayjian , T., Mason, A. E., Westman, E. C., Sethi , S., et al Journal of Eating Disorders. Biomed Central . 2020

  Abstract

  Background: Many patients with obesity and comorbid binge eating symptoms present with the desire to lose weight. Although some studies suggest that dietary restriction can exacerbate binge eating, others show dietary restriction is associated with significant reductions in binge eating. The effect of a particular type of dieting on binge eating, the ketogenic diet (a high fat, moderate protein, very low carbohydrate diet), is not known. Case presentations: We report on the feasibility of a low-carbohydrate ketogenic diet initiated by three patients (age 54, 34, and 63) with obesity (average BMI 43.5 kg/m2) with comorbid binge eating and food addiction symptoms. All patients tolerated following the ketogenic diet (macronutrient proportion 10% carbohydrate, 30% protein, and 60% fat; at least 5040 kJ) for the prescribed period (e.g., 6–7 months) and none reported any major adverse effects. Patients reported significant reductions in binge eating episodes and food addiction symptoms including cravings and lack of control as measured by the Binge-Eating Scale, Yale Food Addiction Scale, or Yale- Brown Obsessive-Compulsive Scale modified for Binge Eating, depending on the case. Additionally, the patients lost a range of 10–24% of their body weight. Participants reported maintenance of treatment gains (with respect to weight, binge eating, and food addiction symptoms) to date of up to 9–17 months after initiation and continued adherence to diet. Conclusions: Although the absence of control cases precludes conclusions regarding the specific role of ketogenic diets versus other forms of dietary restriction, this is the first report to demonstrate the feasibility of prescribing a ketogenic diet for patients with obesity who report binge eating and food addiction symptoms. Further research should seek to reproduce the observed effects in controlled trials as well as to explore potential etiologies. Keywords: Binge eating, Food addiction symptoms, Obesity, Ketogenic diet, Dietary restriction

• Low Carbohydrate Ketogenic Therapy as a Metabolic Treatment for Binge Eating and Ultra-processed Food Addiction. Current Opinion Endocrinology, Diabetes and Obesity Sethi , S., Anika, S., Ashley , G. 2020; 27 (5)

  View details for DOI 10.1097/MED.0000000000000571

• A Randomized, Placebo‐controlled Crossover Trial of Phentermine‐topiramate ER in Patients with Binge‐eating Disorder and Bulimia Nervosa International Journal of Eating Disorders Safer, D. L., Adler, S., Sethi , S., Bentley , J., Toyama, H., Parajito , S., Najarian , T., et al 2019

  View details for DOI 10.1002/eat.23192

• Myths and Facts Regarding Low-Carbohydrate Diets NUTRIENTS Teicholz, N., Croft, S. M., Cuaranta, I., Cucuzzella, M., Glandt, M., Griauzde, D. H., Jerome-Zapadka, K., Kalayjian, T., Murphy, K., Nelson, M., Shanahan, C., Nishida, J. L., Oh, R. C., Parrella, N., Saner, E. M., Sethi, S., Volek, J. S., Williden, M., Wolver, S. 2025; 17 (6)

  View details for DOI 10.3390/nu17061047

  View details for Web of Science ID 001452885800001

• Ketogenic Diets for Body Weight Loss: A Comparison with Other Diets NUTRIENTS Dynka, D., Rodzen, L., Rodzen, M., Pacholak-Klimas, A., Ede, G., Sethi, S., Lojko, D., Barton, K., Berry, K., Deptula, A., Grzywacz, Z., Martin, P., Unwin, J., Unwin, D. 2025; 17 (6)

  View details for DOI 10.3390/nu17060965

  View details for Web of Science ID 001452379100001

• Ketogenic Diet as a Nutritional Metabolic Intervention for Obsessive-Compulsive Disorder: A Narrative Review. Nutrients Lounici, A., Iacob, A., Hongler, K., Mölling, M. A., Drechsler, M., Hersberger, L., Sethi, S., Lang, U. E., Liwinski, T. 2024; 17 (1)

  Abstract

  The substantial evidence supporting the ketogenic diet (KD) in epilepsy management has spurred research into its effects on other neurological and psychiatric conditions. Despite differences in characteristics, symptoms, and underlying mechanisms, these conditions share common pathways that the KD may influence. The KD reverses metabolic dysfunction. Moreover, it has been shown to support neuroprotection through mechanisms such as neuronal energy support, inflammation reduction, amelioration of oxidative stress, and reversing mitochondrial dysfunction. The adequate intake of dietary nutrients is essential for maintaining normal brain functions, and strong evidence supports the role of nutrition in the treatment and prevention of many psychiatric and neurological disorders. Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition marked by persistent, distressing thoughts or impulses (obsessions) and repetitive behaviors performed in response to these obsessions (compulsions). Recent studies have increasingly examined the role of nutrition and metabolic disorders in OCD. This narrative review examines current evidence on the potential role of the KD in the treatment of OCD. We explore research on the KD's effects on psychiatric disorders to assess its potential relevance for OCD treatment. Additionally, we identify key gaps in the preclinical and clinical research that warrant further study in applying the KD as a metabolic therapy for OCD.

  View details for DOI 10.3390/nu17010031

  View details for PubMedID 39796465

  View details for PubMedCentralID PMC11723184

• The effects of ketogenic metabolic therapy on mental health and metabolic outcomes in schizophrenia and bipolar disorder: a randomized controlled clinical trial protocol. Frontiers in nutrition Longhitano, C., Finlay, S., Peachey, I., Swift, J. L., Fayet-Moore, F., Bartle, T., Vos, G., Rudd, D., Shareef, O., Gordon, S., Azghadi, M. R., Campbell, I., Sethi, S., Palmer, C., Sarnyai, Z. 2024; 11: 1444483

  Abstract

  Schizophrenia, schizoaffective disorder, and bipolar affective disorder are debilitating psychiatric conditions characterized by a chronic pattern of emotional, behavioral, and cognitive disturbances. Shared psychopathology includes the pre-eminence of altered affective states, disorders of thoughts, and behavioral control. Additionally, those conditions share epidemiological traits, including significant cardiovascular, metabolic, infectious, and respiratory co-morbidities, resulting in reduced life expectancy of up to 25 years. Nutritional ketosis has been successfully used to treat a range of neurological disorders and preclinical data have convincingly shown potential for its use in animal models of psychotic disorders. More recent data from open clinical trials have pointed toward a dramatic reduction in psychotic, affective, and metabolic symptoms in both schizophrenia and bipolar affective disorder.to investigate the effects of nutritional ketosis via a modified ketogenic diet (MKD) over 14 weeks in stable community patients with bipolar disorder, schizoaffective disorder, or schizophrenia.A randomized placebo-controlled clinical trial of 100 non-hospitalized adult participants with a diagnosis of bipolar disorder, schizoaffective disorder, or schizophrenia who are capable of consenting and willing to change their diets.Dietitian-led and medically supervised ketogenic diet compared to a diet following the Australian Guide to Healthy Eating for 14 weeks.The primary outcomes include psychiatric and cognitive measures, reported as symptom improvement and functional changes in the Positive and Negative Symptoms Scale (PANSS), Young Mania Rating Scale (YMS), Beck Depression Inventory (BDI), WHO Disability Schedule, Affect Lability Scale and the Cambridge Cognitive Battery. The secondary metabolic outcomes include changes in body weight, blood pressure, liver and kidney function tests, lipid profiles, and markers of insulin resistance. Ketone and glucose levels will be used to study the correlation between primary and secondary outcomes. Optional hair cortisol analysis will assess long-term stress and variations in fecal microbiome composition. Autonomic nervous system activity will be measured via wearable devices (OURA ring and EMBRACE wristband) in the form of skin conductance, oximetry, continuous pulse monitoring, respiratory rate, movement tracking, and sleep quality. Based on the encouraging results from established preclinical research, clinical data from other neurodevelopment disorders, and open trials in bipolar disorder and schizophrenia, we predict that the ketogenic metabolic therapy will be well tolerated and result in improved psychiatric and metabolic outcomes as well as global measures of social and community functioning. We additionally predict that a correlation may exist between the level of ketosis achieved and the metabolic, cognitive, and psychiatric outcomes in the intervention group.

  View details for DOI 10.3389/fnut.2024.1444483

  View details for PubMedID 39234289

  View details for PubMedCentralID PMC11371693

• Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry research Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., Westman, E., Krauss, R. M., Saslow, L. 2024; 335: 115866

  Abstract

  The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this treatment has shown promise in the treatment of psychiatric illness. We conducted a 4-month pilot study to investigate the effects of a KD on individuals with schizophrenia or bipolar disorder with existing metabolic abnormalities. Twenty-three participants were enrolled in a single-arm trial. Results showcased improvements in metabolic health, with no participants meeting metabolic syndrome criteria by study conclusion. Adherent individuals experienced significant reduction in weight (12 %), BMI (12 %), waist circumference (13 %), and visceral adipose tissue (36 %). Observed biomarker enhancements in this population include a 27 % decrease in HOMA-IR, and a 25 % drop in triglyceride levels. In psychiatric measurements, participants with schizophrenia showed a 32 % reduction in Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved by an average of 31 %, and the proportion of participants that started with elevated symptomatology improved at least 1-point on CGI (79 %). Psychiatric outcomes across the cohort encompassed increased life satisfaction (17 %) and enhanced sleep quality (19 %). This pilot trial underscores the potential advantages of adjunctive ketogenic dietary treatment in individuals grappling with serious mental illness.

  View details for DOI 10.1016/j.psychres.2024.115866

  View details for PubMedID 38547601

• Correction: Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series. Journal of eating disorders Carmen, M., Safer, D. L., Saslow, L. R., Kalayjian, T., Mason, A. E., Westman, E. C., Sethi, S. 2023; 11 (1): 171

  View details for DOI 10.1186/s40337-023-00881-1

  View details for PubMedID 37773142

  View details for PubMedCentralID 6988301

• Ketogenic Diet as a Metabolic Therapy for Bipolar Disorder: Clinical Developments Journal of Affective Disorders Reports Yu , B., Oz, R., Sethi, S. 2022

  View details for DOI 10.1016/j.jadr.2022.100457

• Ketogenic Diet as a Metabolic Therapy for Bipolar Disorder: Clinical Developments Yu, B., Oz, R., Sethi , S., et al Research Square Preprint . 2021
• Low carbohydrate ketogenic therapy as a metabolic treatment for binge eating and ultraprocessed food addiction. Current opinion in endocrinology, diabetes, and obesity Sethi, S., Sinha, A., Gearhardt, A. N. 2020; 27 (5): 275-282

  Abstract

  The aim of this study was to highlight the recent advancements and future directions for potential use of a low carbohydrate ketogenic dietary approach to treat binge eating and ultraprocessed food addiction. Herein, we explore proposed mechanisms of why a diet low in refined carbohydrates, processed sugar and higher fat content may be helpful in alleviating symptoms.Emerging evidence suggests there may be a metabolic role in development of maladaptive eating. These findings broaden our understanding of eating psychopathology causes. Ultraprocessed, refined or high glycemic index carbohydrates are a possible trigger mediating neurochemical responses similar to addiction. The carbohydrate-insulin model of obesity supports observations of these foods triggering abnormal blood sugar and insulin spikes subsequently leading to changes in metabolic and neurobiological signaling. This results in overeating symptoms and hunger exacerbation, which differs from observed effects of healthy fat consumption and lack of similar insulin spikes. As supported in recent case series, significantly reducing or abstaining from these addictive-like ultraprocessed foods and highly refined carbohydrates could be considered a treatment approach.The current review highlights recent and pertinent evidence with respect to theoretical and practical application of low carbohydrate ketogenic therapeutic approaches for ultraprocessed food addiction and binge eating symptoms. VIDEO ABSTRACT:.

  View details for DOI 10.1097/MED.0000000000000571

  View details for PubMedID 32773576

• Ketogenic diet as a metabolic treatment for mental illness. Current opinion in endocrinology, diabetes, and obesity Norwitz, N. G., Sethi, S., Palmer, C. M. 2020; 27 (5): 269-274

  Abstract

  Ketogenic diets, which have been used to treat drug-refractory paediatric epilepsy for over 100 years, are becoming increasingly popular for the treatment of other neurological conditions, including mental illnesses. We aim to explain how ketogenic diets can improve mental illness biopathology and review the recent clinical literature.Psychiatric conditions, such as schizophrenia, depression, bipolar disorder and binge eating disorder, are neurometabolic diseases that share several common mechanistic biopathologies. These include glucose hypometabolism, neurotransmitter imbalances, oxidative stress and inflammation. There is strong evidence that ketogenic diets can address these four fundamental diseases, and now complementary clinical evidence that ketogenic diets can improve the patients' symptoms.It is important that researchers and clinicians are made aware of the trajectory of the evidence for the implementation of ketogenic diets in mental illnesses, as such a metabolic intervention provides not only a novel form of symptomatic treatment, but one that may be able to directly address the underlying disease mechanisms and, in so doing, also treat burdensome comorbidities (see Video, Supplementary Digital Content 1, http://links.lww.com/COE/A16, which summarizes the contents of this review).

  View details for DOI 10.1097/MED.0000000000000564

  View details for PubMedID 32773571

• Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series. Journal of eating disorders Carmen, M., Safer, D. L., Saslow, L. R., Kalayjian, T., Mason, A. E., Westman, E. C., Sethi Dalai, S. 2020; 8: 2

  Abstract

  Background: Many patients with obesity and comorbid binge eating symptoms present with the desire to lose weight. Although some studies suggest that dietary restriction can exacerbate binge eating, others show dietary restriction is associated with significant reductions in binge eating. The effect of a particular type of dieting on binge eating, the ketogenic diet (a high fat, moderate protein, very low carbohydrate diet), is not known.Case presentations: We report on the feasibility of a low-carbohydrate ketogenic diet initiated by three patients (age 54, 34, and 63) with obesity (average BMI 43.5kg/m2) with comorbid binge eating and food addiction symptoms. All patients tolerated following the ketogenic diet (macronutrient proportion 10% carbohydrate, 30% protein, and 60% fat; at least 5040kJ) for the prescribed period (e.g., 6-7months) and none reported any major adverse effects. Patients reported significant reductions in binge eating episodes and food addiction symptoms including cravings and lack of control as measured by the Binge-Eating Scale, Yale Food Addiction Scale, or Yale-Brown Obsessive-Compulsive Scale modified for Binge Eating, depending on the case. Additionally, the patients lost a range of 10-24% of their body weight. Participants reported maintenance of treatment gains (with respect to weight, binge eating, and food addiction symptoms) to date of up to 9-17months after initiation and continued adherence to diet.Conclusions: Although the absence of control cases precludes conclusions regarding the specific role of ketogenic diets versus other forms of dietary restriction, this is the first report to demonstrate the feasibility of prescribing a ketogenic diet for patients with obesity who report binge eating and food addiction symptoms. Further research should seek to reproduce the observed effects in controlled trials as well as to explore potential etiologies.

  View details for DOI 10.1186/s40337-020-0278-7

  View details for PubMedID 32010444

• If Americans were healthier, we could have been better prepared for this pandemic. Sethi Dalai , S. The Hill Op-Ed. 2020
• Ketogenic Diet as a Metabolic Treatment for Mental Illness. Current Opinion in Endocrinology, Diabetes and Obesity. Norwitz , N., Sethi , S., Palmer , C. 2020 ; 27 (5)

  View details for DOI 10.1097/MED.0000000000000564

• Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa. Contemporary clinical trials Dalai, S. S., Adler, S. n., Najarian, T. n., Safer, D. L. 2018; 64: 173–78

  Abstract

  Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN.Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood.To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design.Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824.

  View details for PubMedID 29038069

• Could Pokémon Go Have Some Mental Health Benefits? Sethi Dalai, S. American Psychiatric Association . Washington DC. 2016