Ketone Supplement + Whey Protein for Muscle Protein Synthesis

Overseen By Tyler Churchward-Venne, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: McGill University

Must not be taking: Anticoagulants, Corticosteroids, HRT, others

Disqualifiers: Pregnancy, Diabetes, Cardiovascular disease, others

Compensation: Varies

Number of Visits: 3

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether ketone supplements, specifically ketone monoester, can boost muscle growth and repair after exercise, particularly when combined with whey protein. Researchers aim to determine if taking ketones alone or with protein enhances muscle protein synthesis (the process of building muscle) more effectively than protein alone or a placebo drink. The study targets adults who are moderately active and regularly include lower-body weightlifting in their routine at least once a week. Participants should maintain stable lifestyle habits and be willing to avoid alcohol and certain medications. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on muscle health and recovery.

Will I have to stop taking my current medications?

The trial requires that you maintain stable use of your current medications and supplements, as long as they are not listed in the exclusion criteria. If your medications are not excluded, you can continue taking them during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the ketone monoester supplement, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is generally safe for people. Studies have found that a single dose, adjusted for body weight, is well-tolerated and effectively increases blood ketone levels, indicating safe use without major concerns.

Whey protein is well-known for aiding muscle growth and is considered safe for most people when used in appropriate amounts. However, individuals with liver or kidney issues should consult a healthcare provider before using it.

The combination of ketone monoester and whey protein also appears safe. Research suggests that using them together does not introduce new safety concerns and may even enhance muscle growth after exercise. Current data supports their safety.

Overall, both ketone monoester and whey protein have a history of being safe and well-tolerated when used as directed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore innovative ways to boost muscle protein synthesis. The ketone monoester supplement is unique because it provides an energy source that doesn't spike blood sugar levels, potentially enhancing muscle recovery and growth more efficiently than traditional carbs or fats. When combined with whey protein, the ketone supplement may further amplify muscle protein synthesis, offering a novel synergy not typically found in standard nutritional strategies. Unlike the standard approach of using only protein supplements, this combination targets energy pathways to optimize muscle-building processes.

What evidence suggests that this trial's treatments could be effective for muscle protein synthesis?

Research has shown that whey protein, one of the treatments in this trial, helps build and repair muscles after exercise, boosting muscle growth within a few hours of working out. Some studies have found that ketone monoester supplements, another treatment option in this trial, increase ketone levels in the blood and aid in muscle building. This trial will also test the combination of ketone supplements with whey protein, as evidence suggests they might enhance muscle growth more than whey protein alone. Although more research is needed, these findings suggest that using both together could be a promising way to maximize muscle building after exercise. ^{1 2 3 6 7}

Who Is on the Research Team?

Tyler Churchward-Venne, PhD

Principal Investigator

Department of Kinesiology and Physical Education, McGill University

Are You a Good Fit for This Trial?

This trial is for individuals who are interested in the effects of diet on muscle growth after resistance exercise. Participants should be healthy and looking to understand how ketone supplements and whey protein affect muscle protein synthesis.

Inclusion Criteria

I can avoid drinking alcohol for 48 hours before the test day.

Moderately active (i.e., ≥ 1 session of lower-body weightlifting /week for the previous 2 months)

I've kept my diet, lifestyle, and weight stable for the last 3 months and will continue to do so.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have a history of blood clots or heart disease.

I have a knee injury, such as an ACL tear.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

10-RM Testing

Participants' 10-repetition maximum (10-RM) is determined for the exercise protocol

1 visit

1 visit (in-person)

Experimental Trial

Participants undergo resistance exercise and receive nutritional treatment with ketone monoester, whey protein, or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in muscle protein synthesis and other metabolic markers

5 hours

Continuous monitoring during the experimental trial

What Are the Treatments Tested in This Trial?

Interventions

• Ketone Monoester

Trial Overview The study tests if a ketone monoester drink can boost muscle building when taken alone or with whey protein after lifting weights, compared to just whey protein or a flavored water control.

How Is the Trial Designed?

Group I: Whey Protein (PRO) Experimental Treatment 2 Interventions

25g of whey protein.

Group II: Ketone Monoester + Whey Protein (KET+PRO) Experimental Treatment 2 Interventions

Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight) and 25g of whey protein.

Group III: Ketone Monoester (KET) Experimental Treatment 2 Interventions

Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight).

Group IV: Placebo drink (CON) Placebo Group 2 Interventions

Flavoured water.

Who Is Running the Clinical Trial?

McGill University

Lead Sponsor

Trials

421

Recruited

1,017,000+

Published Research Related to This Trial

In a study of 27 untrained healthy young adults, both whey and soy protein supplementation during 6 weeks of resistance training significantly increased lean tissue mass and strength compared to a placebo.

The results suggest that while protein supplementation is beneficial, the type of protein (whey vs. soy) does not significantly impact the outcomes in terms of lean tissue mass and strength gains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of whey and soy protein supplementation combined with resistance training in young adults. Candow, DG., Burke, NC., Smith-Palmer, T., et al.[2022]

In a study involving aged mice, a hybrid protein blend (P4) of dairy and plant-based proteins significantly increased muscle protein synthesis (MPS) by 1.5-fold, similar to the 1.6-fold increase seen with whey protein, compared to fasted controls.

The P4 blend showed enhanced postprandial amino acid levels, indicating that its balanced amino acid profile may contribute to MPS stimulation through mechanisms beyond just leucine content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Muscle Protein Synthesis with a Hybrid Dairy and Plant-Based Protein Blend (P4) Is Equal to Whey Protein in a Murine Ageing Model after Fasting. Dijk, FJ., Hofman, Z., Luiking, YC., et al.[2023]

In chronic and acute diseases, muscle wasting is linked to increased protein breakdown in muscles and altered protein synthesis in the liver, influenced by factors like stress and aging.

Dietary interventions, particularly those rich in specific amino acids like leucine, arginine, and citrulline, can enhance muscle protein synthesis and combat muscle wasting in conditions such as cancer and chronic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of specific dietary amino acids in clinical conditions. Jonker, R., Engelen, MP., Deutz, NE.[2021]

Sarcopenia and muscle wasting are expected to increase in older adults due to COVID-19 hospitalizations and lockdowns, driven by factors like physical inactivity and poor diet.

Supplementing meals with whey protein-enriched enteral products, which provide 3-5 g of leucine, can effectively stimulate muscle protein synthesis in older adults, potentially helping to mitigate the risk of sarcopenia during prolonged periods of inactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mTOR1c Activation with the Leucine "Trigger" for Prevention of Sarcopenia in Older Adults During Lockdown. Mai, K., Cando, P., Trasino, SE.[2022]

In a study involving nine boys with Duchenne muscular dystrophy, a supplement of branched-chain ketoacids significantly reduced muscle protein degradation, as indicated by a 14% decrease in 3-methylhistidine excretion (P < 0.01).

The treatment was well-tolerated with no adverse effects reported, suggesting that this ketoacid mixture could be a safe option for managing muscle degradation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched-chain ketoacids reduce muscle protein degradation in Duchenne muscular dystrophy. Stewart, PM., Walser, M., Drachman, DB.[2013]

Intravenous amino acid infusions have a protein-anabolic effect, enhancing protein synthesis and reducing protein degradation, which is crucial for maintaining body protein stores during nutritional interventions.

While carbohydrates do not directly affect protein turnover in humans, lipids, particularly long-chain fatty acids, can inhibit protein breakdown, suggesting that different macronutrients have distinct roles in protein metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of substrates in the regulation of protein metabolism. Tessari, P., Barazzoni, R., Zanetti, M., et al.[2019]

In a study involving minipigs and aged rats, the addition of a carbohydrate energy bolus after whey protein meals did not extend the duration of muscle protein synthesis stimulation in cases of anabolic resistance due to glucocorticoid treatment and aging.

Despite previous findings in healthy individuals suggesting that this strategy could enhance muscle protein synthesis, it proved ineffective in the studied models of muscle wasting, indicating that different approaches may be needed for those experiencing anabolic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post Meal Energy Boluses Do Not Increase the Duration of Muscle Protein Synthesis Stimulation in Two Anabolic Resistant Situations. Mosoni, L., Jarzaguet, M., David, J., et al.[2023]

In a study involving 30 elderly men, soy protein isolate (both 20g and 40g doses) was found to be less effective than whey protein isolate in stimulating muscle protein synthesis (MPS) after resistance exercise, indicating that the type of protein consumed matters for muscle recovery.

The research showed that while higher doses of soy protein did increase MPS compared to no protein, they still did not match the effectiveness of whey protein, likely due to lower levels of leucine in soy and higher rates of amino acid oxidation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. Yang, Y., Churchward-Venne, TA., Burd, NA., et al.[2021]

In a study involving 22 young fit males over a 3-week period, combining collagen peptides with whey protein did not show any significant benefits in muscle recovery or performance compared to whey protein alone after eccentric exercise.

Both groups experienced similar levels of muscle damage and recovery, indicating that adding collagen peptides to a standard whey protein regimen does not enhance recovery outcomes in athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partly Substituting Whey for Collagen Peptide Supplementation Improves Neither Indices of Muscle Damage Nor Recovery of Functional Capacity During Eccentric Exercise Training in Fit Males. Robberechts, R., Poffé, C., Ampe, N., et al.[2023]

Supplementing breakfast with a vitamin D and leucine-enriched whey protein drink significantly increased postprandial muscle protein synthesis in healthy older adults, indicating a beneficial effect on muscle anabolism.

After 6 weeks, participants who consumed the protein drink gained more appendicular lean mass compared to the control group, suggesting that this intervention can help preserve and build muscle mass in older individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementing Breakfast with a Vitamin D and Leucine-Enriched Whey Protein Medical Nutrition Drink Enhances Postprandial Muscle Protein Synthesis and Muscle Mass in Healthy Older Men. Chanet, A., Verlaan, S., Salles, J., et al.[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]

In a study involving healthy human subjects, equimolar doses of branched-chain keto acids (KICA and KMVA) and amino acids (leucine and isoleucine) significantly increased blood levels of both BCKAs and BCAAs, indicating a strong interaction between these compounds.

The results suggest that using keto acid supplements to boost amino acid levels may require higher doses than amino acid supplements, as the presence of keto acids can lead to the catabolism of BCAAs, potentially limiting their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and metabolic interrelationships among branched-chain keto and amino acids in humans. Schauder, P.[2019]

Ingesting 10 g of essential amino acids (EAA) with a typical leucine content (1.8 g) is enough to maximize muscle protein synthesis (MPS) in young adults, indicating that higher leucine concentrations may not be necessary for this effect.

While higher leucine levels (3.5 g) did reduce muscle protein breakdown (MPB) and showed improved mTOR signaling, the overall muscle protein balance was similar between both leucine concentrations, suggesting that leucine may also influence autophagy regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women. Glynn, EL., Fry, CS., Drummond, MJ., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07082309

The Effect of Ketone Monoesters on Skeletal Muscle ... An early study demonstrated that the infusion of BHB stimulates muscle protein synthesis rates (MPS), whilst only a single recent study has investigated the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3810007/

Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R) These results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0002916524000042

Acute ingestion of a ketone monoester, whey protein, or ... The aim of this study was to evaluate the effects of elevated blood β-OHB through oral ingestion of the ketone monoester (R)-3-hydroxybutyl (R)-3- ...

4. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.00310/full

Intake of a Ketone Ester Drink during Recovery from ... KE has recently been shown to improve exercise performance, but whether it can also promote post-exercise muscle protein or glycogen synthesis is unknown.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7442417/

Utility of Ketone Supplementation to Enhance Physical ... Ketone supplements can induce acute ketosis, defined as >0.5 mM βHB in blood, for up to 3 h after consuming a single dose without dietary ...

6. acnfp.food.gov.uk acnfp.food.gov.uk/sites/default/files/mnt/drupal_data/sources/files/multimedia/pdfs/hydroxybester.pdf

3-hydroxybutyl (R)-3-hydroxybutyrate Data related to the safety of (R)-1,3-butanediol and D-β-hydroxybutyrate ester in humans are limited; however, sodium D,L-β-hydroxybutyrate ...

7. nature.com nature.com/articles/s41598-022-14961-w

Efficacy and safety of ketone ester infusion to prevent ... In septic mice, 3-hydroxybutyrate-sodium-salt has shown to partially prevent sepsis-induced muscle weakness.