d-beta-hydroxybutrate for Cognition

Overseen By Anamika Nanda

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Southern California

Disqualifiers: Diabetes, Low blood sugar, others

Compensation: Varies

Number of Visits: 2

Duration: 2 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the supplement d-beta-hydroxybutyrate, combined with exercise, can enhance brain health by increasing BDNF, a protein that supports brain function. The study focuses on individuals with the Met allele genetic marker to assess if they experience greater improvement than those without it. Participants will receive both the actual supplement and a placebo while undergoing exercise tests. Healthy young adults capable of performing aerobic treadmill exercises are ideal candidates for this study. As a Phase 1 trial, the research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

In a previous study, researchers found that d-beta-hydroxybutyrate (BHB) is safe and generally well-tolerated for inducing ketosis. This is the same substance tested in the trial. Some participants might experience mild side effects like an upset stomach or diarrhea, but these are uncommon. Another study showed that BHB can support brain health by reducing inflammation and protecting the brain's barriers, potentially improving thinking and memory skills. Overall, research has used BHB safely, and its potential to support brain function is promising. ^{1 2 3 4 5}

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

Unlike traditional treatments for cognitive decline, which often involve medications targeting neurotransmitter levels, d-beta-hydroxybutyrate is a naturally occurring ketone body that provides an alternative energy source for the brain. Researchers are excited because this compound may enhance brain function by boosting energy metabolism without the side effects associated with many pharmaceuticals. Additionally, it is administered through a simple, sugar-free drink, making it potentially more accessible and easier to integrate into daily routines compared to conventional drugs.

What evidence suggests that this treatment might be an effective treatment for improving cognition?

Studies have shown that beta-hydroxybutyrate (BHB), a substance produced during ketosis, can improve memory and learning. Research indicates that BHB increases blood flow in the brain and enhances thinking skills, particularly when memory problems exist. One study found that people performed better on thinking tests within 90 minutes of taking BHB. Additionally, BHB has been found to repair brain issues caused by a poor diet, supporting healthy brain connections and function. In this trial, participants in the experimental arm will receive a sugar-free electrolyte mixture with d-beta-hydroxybutyrate to assess its potential cognitive benefits. These findings suggest that BHB could boost brain power. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with the Met allele of the BDNF Val66Met SNP, interested in how ketosis and exercise might affect brain health and thinking skills. Participants will take a cognitive test, provide blood samples, and do a treadmill workout during both ketosis supplement and placebo trials.

Inclusion Criteria

Ability to give informed consent

I am a healthy young adult.

I am between 18 and 35 years old.

Exclusion Criteria

Diabetics

I have a history of low blood sugar.

I cannot do an aerobic treadmill test due to limited physical abilities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a ketosis trial and a placebo trial, involving ingestion of a ketosis supplement or placebo, followed by a 30-minute treadmill test

2 days

2 visits (in-person)

Follow-up

Participants are monitored for changes in serum BDNF and cognition after the intervention

1 week

What Are the Treatments Tested in This Trial?

Interventions

• d-beta-hydroxybutyrate

Trial Overview The study tests if d-beta-hydroxybutyrate (a ketosis supplement) combined with physical activity can boost serum BDNF levels and cognition more in people with the Met variant of BDNF than those without it. It involves comparing this supplement's effects to a placebo while exercising on a treadmill.

How Is the Trial Designed?

Group I: Ketosis Trial Experimental Treatment 1 Intervention

Participants will be given a sugar-free electrolyte mixture with d-beta-hydroxybutrate to drink in a 1:1 ratio calculated to 0.1816g/lb based on body weight before the treadmill test.

Group II: Placebo Trial Placebo Group 1 Intervention

Participants consume a placebo consisting of a pure sugar-free electrolyte drink before treadmill test. The grams of placebo will be calculated 0.1816g/lb based on body weight.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0361923022003525

β-hydroxybutyrate improves cognitive impairment caused ... We found that BHB intervention for 8 weeks could effectively restore hippocampal blood flow and improve spatial learning and memory in CCH rats.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15123336/

Effects of beta-hydroxybutyrate on cognition in memory- ... Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.09.17.25335999v1.full-text

The Effect of Exogenous Ketone Bodies on Cognition in ... Results indicate that EK administration has a modest but statistically significant positive effect on cognitive performance (SMD = 0.26, 95% CI ...

4. biorxiv.org biorxiv.org/content/10.1101/2024.01.23.576931v1

BETA-HYDROXYBUTYRATE COUNTERACTS THE ... β-hydroxybutyrate can counteract impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges like saturated ...

5. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12206

A ketogenic drink improves cognition in mild cognitive ... This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11009516/

Evaluation of the safety and tolerability of exogenous ketosis ... Free D-BHB was a safe and well-tolerated intervention for inducing sustained exogenous ketosis. Being bioidentical, salt-free and lacking intermediate ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-1569/beta-hydroxybutyrate-bhb

Beta-Hydroxybutyrate (Bhb) - Uses, Side Effects, and More When taken by mouth: BHB is possibly safe when taken as a single dose of 380 mg/kg. Some people might have stomach upset, diarrhea, constipation ...

8. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1470331/full

Optimizing oral 3-hydroxybutyrate dosage using ... Both reports demonstrated that 3-HB intake had no significant efficacy on cognitive function in healthy subjects (12, 13). However, these ...