Ketone Supplementation for Immune System Function

(Acute_Ketone Trial)

Overseen By Jonathan Little Principal Investigator, Professor Little, Ph.D

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Disqualifiers: Competitive athlete, Ketogenic diet, Pregnancy, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

12 Participants Needed

Trial Summary

What is the purpose of this trial?

To conduct a single-arm pilot study to determine how acute ingestion of an exogenous ketone monoester supplement alters the histone lysine β-hydroxybutyrylation and immune function in healthy human monocytes and lymphocytes.

Do I need to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

Is ketone monoester safe for human use?

Research on ketone monoester, a type of ketone supplement, shows it is generally safe in animals, with no significant toxic effects observed in rats. While human studies are limited, the available data suggest it may be safe, but more research is needed to confirm this in humans. ^{1 2 3 4 5}

How does the drug Ketone Monoester differ from other treatments for immune system function?

Ketone Monoester is unique because it provides exogenous ketones, which can enhance immune function by reprogramming immune cells to use ketones as an energy source, improving their efficiency and response. This approach is different from traditional treatments as it focuses on metabolic changes to boost immunity. ^{1 2 4 6 7}

Eligibility Criteria

This trial is for adults over 19 who can fast overnight. It's not suitable for competitive endurance athletes, pregnant individuals, those with chronic glucose or fat metabolism disorders like type 2 diabetes, or people on ketogenic diets and supplements. Participants must be able to travel to the university and communicate in English.

Inclusion Criteria

I am over 19 years old.

Able to fast overnight

Exclusion Criteria

Being a competitive endurance athlete

Being pregnant

I have a chronic condition like type 2 diabetes or gallbladder disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants consume a ketone monoester supplement and undergo various assessments

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in immune cell function and other physiological parameters

1 day

1 visit (in-person)

Treatment Details

Interventions

• Ketone Monoester

Trial Overview The study investigates how a single dose of an exogenous ketone monoester (KE) supplement affects immune cell function and specific chemical modifications (histone lysine β-hydroxybutyrylation) in healthy human monocytes and lymphocytes.

Participant Groups

Group I: exogenous ketone supplement Experimental Treatment 1 Intervention

Participants will consume a ketone monoester supplement (KetoneAid KE4) at a dose of 0.75 g/kg of body weight.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Findings from Research

Ketone bodies can reprogram CD8+ T-cells in severely ill COVID-19 patients, enhancing their function by increasing cytokine production and cell lysis capacity by up to 24% and 21%, respectively.

This metabolic reprogramming also boosts mitochondrial activity and energy supply in T-cells, suggesting that a ketogenic approach could be a promising strategy to improve immune responses in COVID-19 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone Bodies Improve Human CD8+ Cytotoxic T-Cell Immune Response During COVID-19 Infection. Hirschberger, S., Gellert, L., Effinger, D., et al.[2022]

Exogenous ketone supplements, such as ketone salts or esters, have shown potential benefits for metabolic health, cognitive function, and cardiovascular health, particularly in lowering blood glucose and improving cognitive performance, which may be useful for conditions like type 2 diabetes and neurological diseases.

Current research primarily involves pre-clinical models, and while some human studies support the benefits of exogenous ketones, further clinical validation is needed, especially regarding long-term effects on cardiovascular health and lipid profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exogenous ketone supplementation: an emerging tool for physiologists with potential as a metabolic therapy. Falkenhain, K., Islam, H., Little, JP.[2023]

A 28-day toxicity study in rats showed that (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone monoester, is safe, as it did not cause any significant toxic effects or abnormalities in blood parameters, despite some differences observed.

In a developmental toxicity study, pregnant rats given the ketone monoester showed no adverse effects on pregnancy outcomes or fetal development, further supporting its safety for potential use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate. Clarke, K., Tchabanenko, K., Pawlosky, R., et al.[2022]

A very-low-carbohydrate diet enhances human T-cell responses, including increased capacity of CD4+, CD8+, and regulatory T-cells, as well as improved formation of T memory cells, based on both in vitro studies and an intervention study with healthy volunteers.

The study indicates that ketone bodies trigger significant immunometabolic reprogramming in T cells, promoting better mitochondrial function and energy supply, suggesting that dietary interventions could be a valuable strategy to boost immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very-low-carbohydrate diet enhances human T-cell immunity through immunometabolic reprogramming. Hirschberger, S., Strauß, G., Effinger, D., et al.[2023]

Ketogenic diets (KDs) significantly alter gut microbiota composition, specifically leading to a depletion of bifidobacteria, which is distinct from the effects of high-fat diets (HFDs).

Ketone bodies produced during KDs inhibit the growth of bifidobacteria and are associated with a reduction in pro-inflammatory Th17 cells in the gut, suggesting that KDs may have anti-inflammatory effects through microbiome modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. Ang, QY., Alexander, M., Newman, JC., et al.[2022]

In a study of five patients with chronic renal failure, the addition of keto acid and essential amino acid supplements to their diet significantly improved nitrogen balance and reduced plasma urea levels over two months.

The increase in nitrogen balance observed with keto acids was not fully explained by the reutilization of urea nitrogen, suggesting that keto acids may have a more complex role in promoting protein anabolism beyond just recycling nitrogen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic studies with keto acid diets. Ell, S., Fynn, M., Richards, P., et al.[2018]

In a study with 80 weanling pigs, dietary supplementation with L-leucine (LEU) and its catabolites, alpha-ketoisocaproic acid (KIC) and beta-hydroxymethyl butyrate (HMB), did not negatively impact growth or immune responses over a 6-week period.

However, in a second experiment with 36 pigs, a high concentration of LEU combined with dexamethasone injections led to detrimental effects on both growth and immune function, highlighting the potential risks of excessive LEU intake under certain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of excess dietary leucine and leucine catabolites on growth and immune responses in weanling pigs. Gatnau, R., Zimmerman, DR., Nissen, SL., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Ketone Bodies Improve Human CD8+ Cytotoxic T-Cell Immune Response During COVID-19 Infection. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Exogenous ketone supplementation: an emerging tool for physiologists with potential as a metabolic therapy. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Very-low-carbohydrate diet enhances human T-cell immunity through immunometabolic reprogramming. [2023]

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

Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. [2022]

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

Metabolic studies with keto acid diets. [2018]

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

Effects of excess dietary leucine and leucine catabolites on growth and immune responses in weanling pigs. [2019]