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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a ketone supplement, specifically Ketone Monoester, affects the immune system by examining certain blood cells. The aim is to determine if this supplement alters immune cell function. Participants will take a specific dose of the ketone supplement, and scientists will monitor their immune response. The trial seeks adults over 19 who can fast overnight and do not follow specific diets or have chronic issues with glucose or fat metabolism. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on ketone supplements and immune health.

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.

What prior data suggests that this ketone monoester supplement is safe?

Research has shown that ketone monoester supplements are generally safe for use. One study found that these supplements are safe and well-tolerated by healthy adults over time. The FDA also considers ketone monoesters safe for consumption.

In animal studies, ketone monoesters did not cause harmful effects in rats, suggesting safety, though human studies hold more significance. Additionally, top athletes, such as Tour de France cyclists and Olympians, use these supplements, indicating their trust in their safety.

Overall, current evidence supports the safety of ketone monoester supplements, making them a promising option for those considering participation in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard immune-boosting treatments, which typically involve vitamins, minerals, or herbal supplements, the ketone monoester supplement works by providing an alternative energy source for the body. This supplement, made from ketone monoesters, allows cells to use ketones instead of glucose for energy, which might enhance immune function more efficiently. Researchers are excited about this treatment because it offers a novel way to potentially boost the immune system's response without relying on traditional dietary supplements or medications.

What evidence suggests that ketone monoester supplementation could be effective for immune system function?

Research has shown that ketone monoester supplements, which participants in this trial will receive, can support the immune system. They provide extra ketones, teaching immune cells to use them for energy. Studies have found that beta-hydroxybutyrate (BHB), a type of ketone, might slightly enhance the immune system's ability to fight infections. However, BHB may not fully address issues like high blood sugar, which can weaken the immune response. Overall, early findings suggest that ketone supplements might improve immune function. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

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

Able to fast overnight

I am over 19 years old.

Exclusion Criteria

Being a competitive endurance athlete

Being pregnant

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-immune-functions-9-2024-910b8

Ketone Supplementation 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06590623?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(ketone%20supplement)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING%20OR%20ENROLLING_BY_INVITATION%20OR%20ACTIVE_NOT_RECRUITING))&rank=9

The Effect of Acute Exogenous Oral Ketone ... To conduct a single-arm pilot study to determine how acute ingestion of an exogenous ketone monoester supplement alters the histone lysine β-hydroxybutyrylation ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10929696/

Effect of the ketone beta-hydroxybutyrate on markers of ... Our results indicate that BHB may exert a modest immune function-enhancing effect on oxidative burst but cannot rescue hyperglycaemia-blunted phagocytic ...

4. digitalcommons.library.uab.edu digitalcommons.library.uab.edu/cgi/viewcontent.cgi?article=1457&context=etd-collection

Acceptability and Tolerability of Ketone Supplements and ... In this study, we compared two different commercially available exogenous ketones, a ketone monoester (KME) and a ketone monoester-salt mix (KME+S), at two ...

5. amazon.com amazon.com/KetoneAid-Worlds-Strongest-Exogenous-Caffeine/dp/B07VTL1TT5

KetoneAid Ke4 Ketone Ester Concentrate Provides clean energy for athletic performance, mental clarity, metabolic health, and deep sleep · 12 servings per bottle (144 servings in pack), 2.5 grams of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31655093/

Safety and tolerability of sustained exogenous ketosis ... We conclude that sustained exogenous ketosis using a ketone monoester is safe and well-tolerated by healthy adults.