Keto-Like Supplement for Depression

Overseen By Colleen McCallum

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Laureate Institute for Brain Research, Inc.

Must not be taking: Omega 3, Methadone, Opiates, others

Disqualifiers: Suicidality, Substance use disorder, Psychotic disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 8 weeks

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to determine whether a keto-like supplement relative to placebo results in functional brain changes during fMRI tasks evaluating positive and negative valence in individuals with moderate to severe depression. In this double-blind randomized placebo-controlled trial, 75 individuals with a Patient Health Questionnaire (PHQ-9) scale score ≥ 10 (MDD) will be enrolled to participate in an 8-week treatment study to obtain 60 completers. Participants will be randomized with a 1-1 ratio to receive the keto-like supplement (n= 30 completers) or placebo (n=30 completers) taken orally three times per day for 8 weeks. Participants will undergo a 10.5-hour screening/baseline evaluation visit split over 2 days at week 0 including questionnaires, neuroimaging before and after supplement or placebo administration and blood draws, office visits at week 2 (1.5 hours), week 4 (3 hours), week 6 (0.5 hours), week 8 (6 hours), a follow-up visit at week 10 (1.5 hours) and two phone calls between visits (weeks 1 and 3) during which a brief clinical assessment will be obtained (10 minutes each). The total time involved in the study is approximately 23.5 hours.

Will I have to stop taking my current medications?

Participants must be on stable medications for 6 weeks before joining the study and must stay on the same dose throughout the study, unless their doctor advises otherwise.

What data supports the effectiveness of the Keto-like supplement treatment for depression?

Research suggests that ketogenic diets, which are similar to the Keto-like supplement, have shown benefits in treating neurological and psychiatric disorders. This implies that the metabolic changes induced by such diets might also help with depression. ^{1 2 3 4 5}

Is the Keto-like supplement generally safe for humans?

The ketogenic diet, similar to the Keto-like supplement, has been used safely in humans, particularly for epilepsy and other neurological conditions. However, starting the diet can sometimes cause side effects, so it's often done under medical supervision, especially in children. ^{3 4 6 7 8}

How is the Keto-like supplement treatment for depression different from other treatments?

The Keto-like supplement for depression is unique because it mimics the effects of a ketogenic diet, which alters metabolism to increase ketone levels in the blood, potentially improving mood by enhancing brain energy use and reducing inflammation. Unlike traditional antidepressants, this approach targets metabolic and gut microbiota changes, which may offer benefits for those who do not respond to standard treatments. ^{3 7 9 10 11}

Research Team

Martin Paulus, MD

Principal Investigator

Laureate Institute for Brain Research

Eligibility Criteria

This trial is for individuals with moderate to severe depression, indicated by a score of 10 or higher on the PHQ-9 scale. Participants must be able to commit to an 8-week study with several visits and phone calls, including neuroimaging sessions and blood draws.

Inclusion Criteria

My health is stable according to recent tests and check-ups.

Consent that possible random finding is reported (e.g. brain abnormality during imaging)

Meets the Diagnostic and Statistical Manual - 5 (DSM-5) diagnostic criteria for MDD without psychotic features (past or present), as confirmed by the M.I.N.I v7.0

Exclusion Criteria

I have not fully recovered from a major surgery within the last 12 weeks.

I take Omega 3 fatty acids (like fish oil supplements).

I do not have any major health issues that could interfere with the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person) over 2 days

Treatment

Participants receive the keto-like supplement or placebo three times a day for 8 weeks

8 weeks

4 visits (in-person) at weeks 2, 4, 6, and 8; 2 phone calls at weeks 1 and 3

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person) at week 10

Treatment Details

Interventions

• Keto-like supplement

Trial Overview The study is testing if a keto-like supplement can affect brain responses to emotional stimuli differently than a placebo in depressed individuals. It's a double-blind trial where participants are randomly assigned either the supplement or placebo in equal numbers.

Participant Groups

Group I: Keto-like supplement Active Control 1 Intervention

Participants will receive standardized 9.25g stick packs of the keto-like supplement. The study participants will take one of these stick packs dissolved in water three times a day (morning, noon, and evening) for 8 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive standardized 9.25g stick packs of placebo. The study participants will take one of these stick packs dissolved in water three times a day (morning, noon, and evening) for 8 weeks.

Who Is Running the Clinical Trial?

Laureate Institute for Brain Research, Inc.

Lead Sponsor

Trials

53

Recruited

5,400+

Findings from Research

A review of 11 studies involving 102 cancer patients showed that while ketogenic diets are being explored as a complementary therapy, the evidence regarding their impact on nutritional status, tumor effects, and quality of life is inconclusive.

Adherence to the ketogenic diet was low, with only 49% of participants sticking to it, indicating that more controlled trials are needed to better understand the effectiveness and safety of this dietary approach in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the use of ketogenic diets in adult patients with cancer. Sremanakova, J., Sowerbutts, AM., Burden, S.[2019]

In a study of 31 adults with severe mental illnesses, a ketogenic diet significantly improved depression and psychosis symptoms, as shown by reductions in Hamilton Depression Rating Scale scores from 25.4 to 7.7 and PANSS scores from 91.4 to 49.3, all with P < 0.001.

The ketogenic diet was well-tolerated and also led to improvements in metabolic health markers, including weight, blood pressure, blood glucose, and triglycerides, indicating potential benefits beyond mental health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients. Danan, A., Westman, EC., Saslow, LR., et al.[2022]

In a mouse model of malignant glioma, a ketogenic diet (KetoCal®) significantly increased survival by approximately 5 days compared to a standard diet, indicating its potential as a supportive treatment in cancer therapy.

The combination of the ketogenic diet and radiation therapy showed more than additive effects, with tumor growth significantly reduced in most mice on the ketogenic diet, suggesting that metabolic changes from the diet could enhance the effectiveness of conventional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. Abdelwahab, MG., Fenton, KE., Preul, MC., et al.[2022]

The ketogenic diet (KD), characterized by high fat and low carbohydrate intake, has shown promise in reducing symptoms of various psychiatric disorders based on a review of 14 studies.

While the results indicate a positive response for individuals adhering to the KD, further research is needed to clarify the specific benefits and mechanisms of action in psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of the ketogenic diet in the treatment of psychiatric disorders. Tillery, EE., Ellis, KD., Threatt, TB., et al.[2023]

The restricted ketogenic diet (RKD) targets energy metabolism in malignant brain cancer by reducing glucose and glutamine availability, which are crucial for tumor growth, and has shown anti-cancer effects in mouse models.

Case reports indicate that the RKD can be an effective non-toxic treatment option for malignant gliomas in humans, potentially enhancing the efficacy of existing therapies that also target glucose and glutamine metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Seyfried, TN., Marsh, J., Shelton, LM., et al.[2017]

The ketogenic diet and exogenous ketone supplements can effectively increase serum ketone levels, providing an alternative energy source for high-demand tissues like the brain and heart, which may enhance overall health.

Nutritional ketosis has shown potential therapeutic benefits for various conditions, including heart diseases, epilepsy, mitochondrial diseases, and neurodegenerative disorders, suggesting a growing interest in its application for precision nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention. Saris, CGJ., Timmers, S.[2022]

The ketogenic diet (KD), traditionally used to control seizures in epilepsy, may also improve depressive symptoms by affecting various body systems, including metabolic and immune responses, and altering neurotransmitter levels in the brain.

Research indicates that KD can enhance mitochondrial function and reduce inflammation, which may contribute to its potential antidepressant effects, particularly through changes in gut microbiota associated with major depressive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the mechanisms of action of the antidepressant effect of the ketogenic diet. Ricci, A., Idzikowski, MA., Soares, CN., et al.[2021]

In a study of 66 children with drug-resistant epilepsy, the incidence of adverse events during hospital admission for ketogenic diet (KD) initiation was found to be low at 28.7%, with manageable issues like hypoglycemia and vomiting.

The results suggest that with proper preparation and monitoring, it may be safe to initiate a ketogenic diet at home for carefully selected patients, potentially reducing the need for hospital stays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of potential adverse events during hospital-based ketogenic diet initiation among children with drug-resistant epilepsy. Mir, A., Albaradie, R., Alamri, A., et al.[2022]

Supplementation with folate, particularly in the form of 5-methyltetrahydrofolate (5-MTHF), has shown efficacy in reducing depressive symptoms in various patient groups, including those with low folate levels and the elderly with dementia.

While folate is generally well tolerated and may be safer than other forms, more research is needed to determine optimal dosages and identify which populations will benefit most from folate therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folate in depression: efficacy, safety, differences in formulations, and clinical issues. Fava, M., Mischoulon, D.[2016]

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which are primarily used to treat diabetes, may also induce ketogenesis, potentially enhancing brain energy metabolism and improving mood in individuals with depression.

Research suggests that targeting abnormal brain bioenergetics through ketogenesis could offer a novel therapeutic approach for treating depressive disorders, highlighting the need for further investigation into this mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-Glucose Cotransporter-2 Inhibitors in Depression. Liebers, DT., Ebina, W., Iosifescu, DV.[2023]

Among the five dietary supplements reviewed for treating depression, only omega-3 fatty acids and SAM-e have enough evidence to support their efficacy and safe use.

The FDA's limited ability to regulate dietary supplements means that many products may not have been thoroughly studied for safety and effectiveness before reaching consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary supplement drug therapies for depression. Howland, RH.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

A systematic review of the use of ketogenic diets in adult patients with cancer. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The use of the ketogenic diet in the treatment of psychiatric disorders. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? [2017]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Exploring the mechanisms of action of the antidepressant effect of the ketogenic diet. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Incidence of potential adverse events during hospital-based ketogenic diet initiation among children with drug-resistant epilepsy. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Folate in depression: efficacy, safety, differences in formulations, and clinical issues. [2016]

10. United States pubmed.ncbi.nlm.nih.gov

Sodium-Glucose Cotransporter-2 Inhibitors in Depression. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Dietary supplement drug therapies for depression. [2016]