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?

An acute bout of resistance exercise stimulates muscle protein synthesis (MPS) rates for up to 24-48 hours, supporting muscle growth and repair. To optimize the anabolic effects of resistance exercise, the provision of dietary amino acids (i.e., proteins) is essential. Dietary protein intake provides the body with necessary amounts of essential and non-essential amino acids, which represent the building blocks for muscle proteins, enhancing anabolic muscle growth. The ingestion of dietary protein, such as whey protein, is well established to stimulate an increase in the rate of protein synthesis in skeletal muscle following resistance exercise. Research has demonstrated a dose-dependent relationship between protein intake and MPS rate, with 25 grams being the optimal dose to maximally stimulate MPS rates in younger adults with excess protein oxidized as a fuel source. Determining whether this maximally stimulated MPS response can be further heightened during post-exercise recovery using non-protein dietary factors is yet to be explored. Recently, it has been shown that novel orally ingested ketone body supplements can stimulate MPS rates in younger adults at rest. Ketone bodies (β-OHB) are lipid- derived molecules normally produced under conditions of glucose deprivation (i.e., fasting/starvation, or a low carbohydrate 'ketogenic' diet). However, these orally ingested ketone supplements rapidly increase blood ketone levels without the need for dietary restriction6. In vitro research showed that the combination of leucine and ketone bodies stimulated a 2-fold increase in MPS, compared to the leucine group alone, indicating synergistic effects of protein and ketone bodies on MPS. However, the effect of ketone supplementation, with and without dietary protein co-ingestion, on MPS rate during post-exercise recovery is yet to be investigated. If ketone bodies can amplify the anabolic response to dietary protein, they may provide a novel approach to maximizing muscle adaptation during post-exercise recovery. Therefore, the purpose of this study is to evaluate the effects of ketone monoester intake on postprandial muscle protein synthesis rates when consumed alone and when co-ingested with an optimal dose (25 g) of whey protein during recovery after resistance exercise compared to 1) an optimal dose of whey protein (25 g), and 2) a control flavored water. It is hypothesized that muscle protein synthesis rates will be stimulated following the ingestion of the ketone body beverage. Further, muscle protein synthesis rates will be further enhanced when the ketone-containing beverage and an optimal dose are taken together.

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 the combination of ketone supplements and whey protein safe for humans?

There is no specific safety data available for the combination of ketone supplements and whey protein. However, whey protein is generally considered safe for most people when used appropriately. ^{1 2 3 4 5}

How does the treatment Ketone Monoester with Whey Protein differ from other treatments for muscle protein synthesis?

The combination of Ketone Monoester and Whey Protein is unique because it potentially enhances muscle protein synthesis by providing both a rapid source of energy and high-quality protein. Ketone Monoester can quickly increase ketone levels in the blood, which may support energy metabolism, while Whey Protein is rich in essential amino acids that are crucial for muscle building. ^{2 6 7 8 9}

What evidence supports the effectiveness of the treatment Ketone Monoester combined with Whey Protein for muscle protein synthesis?

Research suggests that branched-chain ketoacids, similar to ketone monoesters, can reduce muscle protein breakdown, which may help in conditions like Duchenne muscular dystrophy. Additionally, leucine, a component of whey protein, is known to stimulate muscle protein synthesis, indicating potential benefits for muscle health. ^{8 10 11 12 13}

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 bone or muscle condition.

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 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]

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]

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 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]

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 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]

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 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]

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]

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 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]

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]

Citations

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

Branched-chain ketoacids reduce muscle protein degradation in Duchenne muscular dystrophy. [2013]

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

Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Post Meal Energy Boluses Do Not Increase the Duration of Muscle Protein Synthesis Stimulation in Two Anabolic Resistant Situations. [2023]

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

Role of specific dietary amino acids in clinical conditions. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The role of substrates in the regulation of protein metabolism. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. [2021]

7. United States 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. [2023]

8. United States 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. [2023]

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

Effect of whey and soy protein supplementation combined with resistance training in young adults. [2022]

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

mTOR1c Activation with the Leucine "Trigger" for Prevention of Sarcopenia in Older Adults During Lockdown. [2022]

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

Metabolic studies with keto acid diets. [2018]

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

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

13. Switzerland 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. [2023]