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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a keto-like supplement (a dietary supplement similar to a ketogenic diet) can alter brain function in people with moderate to severe depression. Participants will receive either the supplement or a placebo (a look-alike with no active ingredients) for eight weeks to assess its impact on mood and brain activity. The trial seeks individuals who have experienced moderate to severe depression for an extended period and are stable on their current medications. Those experiencing depression and willing to try a new supplement may find this trial suitable. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ketogenic diets, similar to the keto-like supplement under study, can aid in managing mental health conditions. These supplements are usually considered safe, containing ingredients like beta-hydroxybutyrate and acetoacetate salts, which are generally recognized as safe. Although specific safety data for this particular supplement is limited, its composition of well-known components suggests it is likely safe. However, testing of this supplement continues, and researchers are still learning about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Unlike the standard treatments for depression, which often include medications like SSRIs (Selective Serotonin Reuptake Inhibitors) or SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors), the keto-like supplement under investigation offers a novel approach by potentially influencing brain metabolism through dietary intervention. This supplement mimics the effects of a ketogenic diet, which may alter brain energy utilization and neurotransmitter balance, offering a unique mechanism that could provide benefits not seen with traditional antidepressants. Researchers are excited about this treatment because it could offer an alternative for those who don't respond well to existing medications, and it may present fewer side effects by leveraging a more natural, dietary-based method.

What evidence suggests that this keto-like supplement might be an effective treatment for depression?

Research suggests that a keto-like supplement, which participants in this trial may receive, might help with depression. One study showed that people with major depression experienced complete relief within 7 to 12 weeks using a nutritional ketosis approach. Another study found that a ketogenic diet could stabilize the brain in people with severe mental illness. Evidence also shows that many participants improved in both depression and anxiety when following a low-carbohydrate ketogenic diet. However, some research indicates a link between higher ketone levels and depression, though this doesn't imply a direct cause. Overall, early findings are promising, but more research is needed to confirm these results. ^{1 2 6 7 8}

Who Is on the Research Team?

Martin Paulus, MD

Principal Investigator

Laureate Institute for Brain Research

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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 (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]

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]

Citations

1. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1396685/full

Complete remission of depression and anxiety using a ... Complete remission of major depression and generalized anxiety disorder occurred within 7–12 weeks of therapeutic nutritional ketosis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6543248/

Therapeutic Potential of Exogenous Ketone Supplement ... The aim of this review is to summarize the current information on ketone supplementation as a potential therapeutic tool for psychiatric disorders.

3. med.stanford.edu med.stanford.edu/news/all-news/2024/04/keto-diet-mental-illness.html

Pilot study shows ketogenic diet improves severe mental illness A small clinical trial led by Stanford Medicine found that the metabolic effects of a ketogenic diet may help stabilize the brain.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0165032725010365

Association between ketone metabolism and the risk of ... There was observational evidence that higher KB concentration was associated with an increased risk of depression, but MR suggests this is not causal.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10134254/

Efficacy of low carbohydrate and ketogenic diets in treating ... The first study reported improvements in anxiety, depression and 'dysperception' in 82% of participants. Similarly, the second study reported improvements in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9705794/

Ketogenic diets and Ketone suplementation: A strategy for ... Beta-hydroxybutyrate and acetoacetate salts and/or amino acids, and esters, and MCT supplementation is commercially available and generally considered as safe.

7. withpower.com withpower.com/trial/phase-2-depression-2024-b59e7

Keto-Like Supplement for Depression Research suggests that ketogenic diets, which are similar to the Keto-like supplement, have shown benefits in treating neurological and psychiatric disorders.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0165178124001513

Ketogenic Diet Intervention on Metabolic and Psychiatric ... Ketogenic diet therapy resulted in metabolic syndrome reversal in this cohort of serious mental illness. •. Participants with schizophrenia showed an ...