Impact of a Ketogenic Diet on Metabolic and Psychiatric Health in Patients With Bipolar or Schizophrenia Illness

Impact of A Low-Carbohydrate, High-Fat, Ketogenic Diet on Obesity, Metabolic Abnormalities and Psychiatric Symptoms in Patients With Bipolar or Schizophrenia Illness: A Pilot Trial

To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with either schizophrenia or bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects.

Study Overview

• Status: Completed
• Conditions: Obesity; Schizophrenia; Metabolic Syndrome; Bipolar Disorder; Weight Gain; Ketogenic Dieting; Psychotropic Agents Causing Adverse Effects in Therapeutic Use; Brain Metabolic Disorder
• Intervention / Treatment: Other: LCHF, Ketogenic Diet

Detailed Description

Adults with mental illness represent a high-risk, marginalized group in the current metabolic and obesity epidemic. Among US adults with severe mental illness, metabolic syndrome are highly prevalent conditions having severe consequences, with patients estimated to die on average 25 years earlier than the general population largely of premature cardiovascular disease. Many psychiatric medications, particularly neuroleptics and mood stabilizers, may, in addition, contribute to metabolic side effects and weight gain. Low-carbohydrate high-fat (LCHF) or ketogenic diets (KD) have been shown to reduce cardiovascular risk in those with insulin resistance. Recent findings support the idea that bipolar disorder, along with other psychiatric diseases schizophrenia, may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction which has downstream effects on synapse connections. A KD diet provides alternative fuel to the brain aside from glucose and is believed to contain beneficial neuroprotective effects, including stabilization of brain networks, reduction of inflammation and oxidative stress. The purpose of this study is to evaluate both the metabolic and psychiatric outcomes with a KD diet in this psychiatric population.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Department of Psychiatry & Behavioral Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-75 years old
2. Meet DSM V criteria for schizophrenia or bipolar disorder, any subtype, for > 1 year and clinically stable (with no hospitalization for past 3 months)
3. Currently taking psychotropic medication and gained at least 5% weight since starting medication or have a BMI greater than or equal to 26 kg/m2 or presence of at least one metabolic abnormality (hypertriglyceridemia, insulin resistance, dyslipidemia, impaired glucose tolerance)
4. Willing to consent to all study procedures and attend follow-up appointments and motivated to follow the dietary program.
5. Sufficient control over their food intake to adhere to study diets.
6. Willingness to regularly monitor blood pressure, glucose, dietary intake, and body weight over the 4-month trial

Exclusion Criteria:

1. Any subject pregnant or nursing
2. Comorbidity of developmental delay
3. Active substance abuse with illicit drugs or alcohol
4. In a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary program.
5. Anyone who has been hospitalized or taken clozapine over the past 3 months
6. Inability to complete baseline measurements
7. Severe renal or hepatic insufficiency

8. Cardiovascular dysfunction, including diagnosis of:

   1. Congestive heart failure
   2. Angina
   3. Arrhythmias
   4. Cardiomyopathy
   5. Valvular heart disease
9. Any other medical condition that may make either diet dangerous as determined by the study medical team (e.g. anorexia nervosa)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketogenic Diet 16 Week Group; Patients follow ketogenic diet for 16 weeks, with monitoring of physical and psychological health and coaching support	Other: LCHF, Ketogenic Diet; Low Carbohydrate, Moderate Protein, High Fat Ketogenic Dietary Intervention 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in heart rate from baseline	Heart rate recorded at 9 visits during study	Baseline, 16 weeks
Change in blood pressure from baseline	Blood pressure recorded at 9 visits during study	Baseline, 16 weeks
Change in weight from baseline	Weight recorded at 9 visits during study	Baseline, 16 weeks
Change in waist circumference from baseline	waist circumference measured at 9 visits during study	Baseline, 16 weeks
Change in visceral fat mass from baseline	Body composition (SECA) recorded at 5 visits during study	Baseline, 16 weeks
Change in body fat mass from baseline	Body composition (SECA) recorded at 5 visits during study	Baseline, 16 weeks
Percent Change in Hemoglobin A1c from baseline	Hemoglobin A1c recorded at initial and final visits	Baseline, 16 weeks
Change in insulin resistance measure (HOMA-IR) from baseline	HOMA-IR measured at initial and final visits	Baseline, 16 weeks
Change in inflammatory marker (hsCRP) from baseline	hsCRP measured at initial and final visits	Baseline, 16 weeks
Change in lipid profile TG (triglycerides) from baseline	Lipid profile TG measured at initial and final visits	Baseline, 16 weeks
Change in lipid profile small LDL (small dense LDL) from baseline	Lipid profile small LDL measured at initial and final visits	Baseline, 16 weeks
Change in lipid profile (HDL) from baseline	Lipid profile HDL measured at initial and final visits	Baseline,16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychiatric Indices - Mood	Change in Mood Qualitative Score (Clinical Mood Monitoring) from baseline	Baseline, 16 weeks
Psychiatric Indices- Clinical Global Impression	Change in Clinical Global Impression Scales (CGI) from baseline 1-7 scale. 1= not at all ill, 7= among the most extremely ill patients)	Baseline, 16 weeks
Generalized Anxiety Disorder - GAD-7 Anxiety	Change in Generalized Anxiety Symptom (GAD-7) scale from baseline. 0-15+ scale. (0= no anxiety, 15+= severe anxiety)	Baseline, 16 weeks
Patient Health Questionnaire - PHQ-9 Depression	Change in Patient Health Questionnaire (PHQ-9) from baseline. Score range 0-27 (0= no depression, 27= severe depression)	Baseline, 16 weeks
Psychiatric Indices- Global Assessment of Functioning	Change in Global Assessment of Functioning (GAF) Scale from baseline. 1-100 scale (1= persistent danger of hurting self or others, 100= superior functioning)	Baseline, 16 weeks
Psychiatric Indices- Quality of Life	Change in Manchester Quality of Life Scale (MANSA) from baseline. Range 12-84 (each of 12 outcomes rated from 1= could not be worse to 7= could not be better; <4= dissatisfied with QoL, >4= satisfied with QoL)	Baseline, 16 weeks
Psychiatric Indices- BPRS	Change in Brief Psychiatric Rating Scale (BPRS) from baseline. Score range 18-126. (For each of 18 symptoms, 1=symptom not present, 7= extremely severe)	Baseline, 16 weeks
Pittsburgh Sleep Quality Index - PSQI	Change in Pittsburgh Sleep Quality Index from baseline. 0-21 scale (<5=good sleeper; 5+= meaningfully disturbed sleep or poor sleeper)	Baseline, 16 weeks

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Shebani Sethi Dalai, MD, Stanford University

Publications and helpful links

General Publications

• Brietzke E, Mansur RB, Subramaniapillai M, Balanzá-Martínez V, Vinberg M, González-Pinto A, Rosenblat JD, Ho R, McIntyre RS. Ketogenic diet as a metabolic therapy for mood disorders: Evidence and developments. Neurosci Biobehav Rev. 2018 Nov;94:11-16. doi: 10.1016/j.neubiorev.2018.07.020. Epub 2018 Jul 31. Review.
• Sethi Dalai S, Sinha A, Gearhardt AN. Low carbohydrate ketogenic therapy as a metabolic treatment for binge eating and ultraprocessed food addiction. Curr Opin Endocrinol Diabetes Obes. 2020 Oct;27(5):275-282. doi: 10.1097/MED.0000000000000571.
• Carmen M, Safer DL, Saslow LR, Kalayjian T, Mason AE, Westman EC, Sethi Dalai S. Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series. J Eat Disord. 2020 Jan 29;8:2. doi: 10.1186/s40337-020-0278-7. eCollection 2020.
• Norwitz NG, Dalai SS, Palmer CM. Ketogenic diet as a metabolic treatment for mental illness. Curr Opin Endocrinol Diabetes Obes. 2020 Oct;27(5):269-274. doi: 10.1097/MED.0000000000000564.
• Yu B, Ozveren R, Sethi Dalai S. Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments. Submitted to Journal of Affective Disorders. Research Square preprint March 2020: DOI is: 10.21203/rs.3.rs-334453/v1
• Sarnyai Z, Kraeuter AK, Palmer CM. Ketogenic diet for schizophrenia: clinical implication. Curr Opin Psychiatry. 2019 Sep;32(5):394-401. doi: 10.1097/YCO.0000000000000535.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2019
• Primary Completion (Actual): August 11, 2022
• Study Completion (Actual): August 11, 2022

Study Registration Dates

• First Submitted: April 30, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (Actual): May 2, 2019

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Glucose Metabolism Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Schizophrenia Spectrum and Other Psychotic Disorders; Insulin Resistance; Hyperinsulinism; Body Weight Changes; Bipolar and Related Disorders; Obesity; Schizophrenia; Disease; Metabolic Syndrome; Bipolar Disorder; Weight Gain; Metabolic Diseases; Brain Diseases, Metabolic
• Other Study ID Numbers: 48527

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No