Study explores whether added ketones amplify anabolic effect of a ‘sub-optimal’ protein dose

By Asia Sherman

- Last updated on GMT


Related tags exogenous ketones Protein Muscle protein synthesis

Ketone supplementation may promote growth of skeletal muscle, but little is known about how it affects muscle protein synthesis when combined with dietary protein.

In a recent study, researchers from McGill University compared the effects of exogenous ketones (DeltaG, TDeltaS Ltd, UK) with and without protein (Isagenix, AZ, USA) to protein alone on myofibrillar protein synthesis (MyoPS) in a group of young males. 

“In addition to serving as a fuel source, β-OHB (the primary ketone body in circulation) is now recognized as a signaling metabolite that can modulate an array of physiological functions including substrate metabolism, inflammation, oxidative stress and gene expression in multiple organs including skeletal muscle,” the researchers wrote in The American Journal of Clinical Nutrition​. 

MyoPS is primarily responsible for changes in skeletal muscle mass following resistance training and is short-lived. It is widely adopted as proxy for gauging the chronic efficacy of acute interventions.

Stimulating muscle protein synthesis

Muscle protein synthesis is essential for exercise recovery and adaptation, and the role of ketone bodies in the regulation of whole-body and muscle protein metabolism has been a topic of interest for decades, the study noted. 

Given the established dose-response relationship between protein/essential amino acid ingestion and postprandial muscle protein synthesis rates, whereby ingestion of 20 g high-quality protein​ or 10 g of essential amino acids (EAA)​ maximally stimulates postprandial MPS rates in young males, the researchers hypothesized that protein would increase MyoPS rates above basal conditions (i.e., overnight post-absorptive conditions). 

“We further hypothesized that KET would stimulate MyoPS rates above basal conditions; however, KET+PRO would stimulate greater MyoPS rates than both KET and PRO alone due to ketone bodies amplifying the anabolic effect of a ‘sub-optimal’ 10 g dose of protein,” they wrote, noting the potential role of the mTORC1 signaling pathway in the process.

According to a position stand published by the International Society of Sports Nutrition (ISSN)​, general recommendations for optimal protein intake per serving for athletes to maximize muscle protein synthesis are 0.25 g of a high-quality protein per kg of body weight, or an absolute dose of 20–40 g.

Study details

The randomized, double-blind, parallel group study recruited 36 healthy recreationally active young males who reported to the laboratory for a single test visit after a 10-hour overnight fast, where they received a primed continuous infusion of stable isotope tracer L-[ring​-2​H5​]-phenylalanine.

Participants, evenly distributed among three test groups, then consumed nutritional beverages that contained either a ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 10 g whey protein (PRO) or a combination of the two (KET+PRO).

Blood was collected at baseline and at intervals post-intervention to assess ketone body β-hydroxybutyrate, glucose, insulin and amino acid concentrations, and muscle biopsies were used to compare MyoPS rates and mTORC1 pathway signaling among groups.

Findings showed that ketone monoester co-ingestion with dietary protein augmented postprandial plasma leucine, essential amino acids and total amino acid concentration compared to dietary protein without the ketone monoester.  

“Despite differences in postprandial plasma aminoacidemia, acute ingestion of a ketone monoester (0.36 g · kg-1​ body weight) eliciting a β-OHB Cmax​ of ∼3.2 mmol∙L-1​, 10 g whey protein, or their co-ingestion in the overnight postabsorptive [fasting] state elicit similar increases in postprandial MyoPS rates in vivo​ in healthy young males,” the researchers concluded. 

Regarding mechanism of action, they noted that mTORC1 pathway signaling responses did not differ between treatments at the time-points examined.


Source: The American Journal of Clinical Nutrition
“Acute ingestion of a ketone monoester, whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of myofibrillar protein synthesis rates in young males: a double-blind randomized trial”
Authors: Sarkis J. Hannaian et al.

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