Ketogenic Diet for Depression

NCT06105762 | Not Yet Recruiting

• 1 other identifier: KET6O1L
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

Globally, it's estimated that around 300 million people are affected by depressive illness, and even with access to modern mental health care, long-term recovery is uncommon. Recently, there has been increasing interest in a promising intervention: the ketogenic diet. This diet restricts carbohydrate intake, promoting the breakdown of fats into circulating ketone bodies, which can act as an additional energy source for the brain, potentially reducing its reliance on glucose. While various sources of evidence suggest the potential benefits of the ketogenic diet for individuals with depression, robust clinical studies on its efficacy in depressed patients are lacking. Our goal is to conduct an eight-week, assessor-blinded, randomized controlled trial to investigate the therapeutic effects of a very low-carbohydrate, high-fat ketogenic diet compared to an active comparator diet in individuals with depression.

Conditions

Depressive Disorder; Major Depressive Disorder; Depression, Bipolar

Outcome Measures

Primary Outcomes (1)

• Depressive Symptoms Severity

  * Assessment Tool: Hamilton Depression Rating Scale (HAM-D17) * Scale Range: 0 to 54 (higher scores indicate more severe depressive symptoms)

  Baseline (week 0), week 4, week 8

Secondary Outcomes (9)

• Anxiety Symptoms Severity

  Baseline (week 0), week 4, week 8

• Functioning

  Baseline (week 0), week 4, week 8

• Hedonic Tone

  Baseline (week 0), week 4, week 8

• Sleep Quality

  Baseline (week 0), week 4, week 8

• Subjective Depressive Symptom Burden

  Baseline (week 0), week 4, week 8

Study Arms (2)

Ketogenic Diet Arm

EXPERIMENTAL

During an 8-week period, individuals enrolled in the experimental group will undergo a low-carbohydrate, high-fat ketogenic diet intervention. We will implement the Modified Atkins Diet (MAD), which is a nutritionally rich and diverse variant of the ketogenic diet. It restricts net carbohydrate intake to less than 20g per day.

Other: Ketogenic Diet

Conventional Healthy Mixed Diet Arm

ACTIVE COMPARATOR

The control group will be provided with a standard balanced mixed diet following the recommendations for healthy nutrition by the Schweizerische Gesellschaft für Ernährung (Société Suisse de Nutrition). This diet will consist of an average daily caloric supply from carbohydrates of approximately 45 - 60%, as per the guidelines.

Other: Ketogenic Diet

Interventions

Ketogenic Diet OTHER

The ketogenic diet intervention, administered as a Modified Atkins Diet, involves a significantly reduced daily carbohydrate intake, typically less than 20 grams of net carbs. This approach primarily relies on higher fat consumption to induce ketosis, a metabolic state characterized by elevated ketone body production, serving as an alternative brain fuel source.

Also known as: LCHF (Low-Carb, High-Fat) Diet, Keto Diet, Modified Atkins Diet, Carb-Restricted Diet

Conventional Healthy Mixed Diet Arm; Ketogenic Diet Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unequivocal diagnosis of major depressive disorder or bipolar depression according to ICD-10 and ICD-11 (as soon as approved in Switzerland) criteria
• Age ≥18 years
• The patient can give informed consent as documented by signature
• Interest in trying a dietary intervention
• Participants must refrain from using any non-prescribed psychotropic agents during the study period including alcohol and illicit drugs such as cannabis; long term pain medication, caffeine and nicotine are excluded from that rule

You may not qualify if:

• Inability to follow the study procedures, e.g., because of a language barrier, neurological and interfering mental disorders, dementia
• Anorexia nervosa
• BMI \<18.5 kg/m2
• Pregnancy or breast feeding
• Current electroconvulsive therapy (ECT)
• Concurrent ketamine therapy
• Inability to follow the procedures of the study, e.g. due to language barrier, neurological and interfering mental disorders, high-grade dementia, etc.
• Porphyria
• Type 1 diabetes
• Insulin-dependent type 2 diabetes
• Contraindicated medical conditions; besides rare hereditary metabolic disorders (typically diagnosed in childhood), contraindications comprise acute pancreatitis, nephrolithiasis, advanced renal failure, advanced liver failure, advanced congestive heart failure, advanced pulmonary disease with respiratory failure, and concurrent use of SGLT2 inhibitors

Sponsors & Collaborators

• University Psychiatric Clinics Basel: lead

Related Publications (6)

• Francis H, Stevenson R. The longer-term impacts of Western diet on human cognition and the brain. Appetite. 2013 Apr;63:119-28. doi: 10.1016/j.appet.2012.12.018. Epub 2013 Jan 3.

  PMID: 23291218 RESULT

• Gangwisch JE, Hale L, Garcia L, Malaspina D, Opler MG, Payne ME, Rossom RC, Lane D. High glycemic index diet as a risk factor for depression: analyses from the Women's Health Initiative. Am J Clin Nutr. 2015 Aug;102(2):454-63. doi: 10.3945/ajcn.114.103846. Epub 2015 Jun 24.

  PMID: 26109579 RESULT

• Wheless JW. History of the ketogenic diet. Epilepsia. 2008 Nov;49 Suppl 8:3-5. doi: 10.1111/j.1528-1167.2008.01821.x.

  PMID: 19049574 RESULT

• Mentzelou M, Dakanalis A, Vasios GK, Gialeli M, Papadopoulou SK, Giaginis C. The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice. Nutrients. 2023 May 11;15(10):2270. doi: 10.3390/nu15102270.

  PMID: 37242153 RESULT

• Smolensky IV, Zajac-Bakri K, Gass P, Inta D. Ketogenic diet for mood disorders from animal models to clinical application. J Neural Transm (Vienna). 2023 Sep;130(9):1195-1205. doi: 10.1007/s00702-023-02620-x. Epub 2023 Mar 21.

  PMID: 36943505 RESULT

• Norwitz NG, Sethi S, 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.

  PMID: 32773571 RESULT

MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Major; Bipolar Disorder

Interventions

Diet, Ketogenic; Diet

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Central Study Contacts

Timur Liwinski

CONTACT

+41 61 325 5544; Timur.Liwinski@upk.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: October 30, 2023
• Study Start: January 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: October 30, 2023

Record last verified: 2023-10