Skip to content

Effects of ketone supplementation on recovery from endurance exercise in recreationally active males

Effects of ketone supplementation on rates of muscle protein synthesis following leg cycling in recreational active males

Status
Not yet recruiting
Phases
Unknown
Study type
Interventional
Source
ANZCTR
Registry ID
ACTRN12623000184673
Acronym
KAPER (Ketones and Post-Exercise Recovery)
Enrollment
10
Registered
2023-02-21
Start date
2023-02-28
Completion date
2023-09-04
Last updated
2023-02-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Athletes across many disciplines engage in structured, periodized training plans to promote adaptation and ultimately optimise performance. However, recent research has made it clear that manipulating the provision of nutritional support throughout training and during the recovery periods can play an equally important a role in determining performance outcomes. Over the last 20+ years, exercise science research has primarily focused on the provision of carbohydrate and protein to facilitate glycogen replenishment and skeletal muscle repair, respectively. More recently, scientific studies have begun exploring whether supplementing with beverages containing ketone esters may provide an alternative fuel source to support exercise and subsequent recovery. To date, the evidence to support ketone use during exercise is mixed, but there have been promising findings suggesting that this fuel may promote muscle repair, and may reduce the likelihood of athletes developing symptoms of overtraining. While the finding that exogenous ketones may increase the activity of the machinery response for building new proteins is exciting; it remains to be determined whether supplementing with ketones can increase the rate of muscle protein synthesis (MPS) following exercise. Therefore, the primary aim of this study is to measure the effects of a ketone supplement or energy-matched placebo on MPS following an acute bout of endurance exercise in trained cyclists. In addition to a proposed enhancement of muscle repair and adaptation, the intake of ketone esters is claimed to act as an appetite suppressant to assist with the aggressive manipulation of physique prized by many road cyclists. Indeed, despite reports of an increased energy intake and reduction in markers of over-reaching in a ketone-supplemented group following intensified cycling training, there have been observations of suppression of hormones linked to hunger (e.g., ghrelin), self-reported hunger and desire to eat in the hours following the intake of ketone ester supplements in sedentary humans and supportive evidence in rodent models. Other effects associated with post-exercise ketosis achieved via adaptation to a ketogenic diet also merit investigation in relation to the post-exercise supplementation with ketone esters; these include alterations to iron and bone metabolism. Therefore, the secondary aim of this study is to examine the effect of ketone ester supplementation on other effects on post-exercise recover including impacts on hunger and appetite, as well as on markers linked to iron metabolism and bone health.

Interventions

10 well-trained male cyclists/triathletes (A-B grade, training >200km/week, 18-35 years old, BMI 18.5 – 24.9 kg/m^2) will be included in this randomised, double-blind placebo-controlled cross-over study. Prior to the first training session, all participants will complete preliminary testing including a 3-day food record, body composition scan (DXA), fitness testing (VO2peak test) and exercise session familiarisation. During the experimental visits, a total of 3 muscle biopsies and 10 blood sam

10 well-trained male cyclists/triathletes (A-B grade, training >200km/week, 18-35 years old, BMI 18.5 – 24.9 kg/m^2) will be included in this randomised, double-blind placebo-controlled cross-over study. Prior to the first training session, all participants will complete preliminary testing including a 3-day food record, body composition scan (DXA), fitness testing (VO2peak test) and exercise session familiarisation. During the experimental visits, a total of 3 muscle biopsies and 10 blood samples (~10 mL / sample) will be obtained from each participant. Participants will complete a total of two experimental exercise sessions with 1-2 weeks of recovery between sessions. The first exercise session of the experimental period will involve random selection for supplementation with either a commercially available ketone ester (KE) or energy-matched placebo (PL), and the second session will involve a single session supplementing with the opposite treatment (i.e., what was not consumed in the first exercise session). Participants will keep a food record and receive dietary instruction from accredited dietitians to meet individual energy targets prior to the two exercise sessions. On experimental days, participants will report do the lab following an overnight fast. A Teflon catheter will then be inserted into an antecubital (inside of elbow) vein for basal blood collection. A second catheter will be inserted into a pre-heated vein of the opposite hand for blood collection. Following basal blood collection, the plasma phenylalanine pool will be primed with an intravenous dose of L-[ring-(13)C(6)]-phenylalanine and directly thereafter a continuous tracer infusion will commence and participants will be provided with a low-protein, carbohydrate (CHO) rich breakfast (e.g., ~2.0g/kg body mass (BM) CHO, <0.2g/kg BM protein). Participants will then complete a supervised leg-cycling exercise protocol consisting of 6x30 min continuous blocks of alternating intensities to mimic a cycling road race. Upon completion of the exercise protocol, a first muscle biopsy will be taken from the vastus lateralis muscle to determine the background enrichment and basal muscle protein synthetic rate. Participants will then be fed a recovery beverage containing carbohydrate and protein consistent with current dietary post-exercise recommendations (3g/kg BM CHO, 25 g protein) well as either a ketone ester (573 mg/kg) or taste-matched placebo (bitter tasting solution containing sucrose octaacetate dissolved in water), with a maintenance dose (286 mg/kg ketone or placebo) consumed every hour (i.e., at 1, 2, 3 and 4 h post exercise) to maintain circulating ketone availability. To determine post-prandial muscle protein synthesis, another 2 biopsies will be taken at 2 h and 5 h post exercise. Participants will then be provided with a self-serve buffet style dinner where they can self-select from a range of healthy, nutritious foods in accordance with their personal preferences. During this time (~45 min), they will be asked to fill out several surveys related to feelings of hunger, fullness, and GI upset/discomfort. Participants will remain in the lab under supervision for the full duration of the experimental visit.

Sponsors

Dr Jamie Whitfield
Lead SponsorIndividual

Study design

Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)

Eligibility

Sex/Gender
Male
Age
18 Years to 35 Years
Healthy volunteers
Yes

Inclusion criteria

Participants will be recruited if they meet the following criteria: • Male • Aged 18-35 y • BMI: 18.5-24.9 kg/m2 • Recreationally active (A-B grade cyclists or triathletes currently cycling ~200km/week) capable of completing the 180 min intermittent intensity exercise protocol • No cardiopulmonary abnormalities • No injuries • Pass the ESSA pre-exercise screening tool and/or obtain GP clearance to exercise

Exclusion criteria

Exclusion criteria: • Known cardiovascular disease or diabetes mellitus • Known bleeding disorder (i.e. hemophilia A [factor VIII deficiency] • Hemophilia B [factor IX deficiency] • von Willebrand disease, or other rare factor deficiencies including I, II, V, VII, X, XI, XII and XIII) • Major or chronic illness that impairs mobility or eating/digestion • Taking prescription medications (i.e. beta-blockers, anti-arrhythmic drugs, statins, insulin sensitising drugs, or drugs that increase the risk of bleeding [i.e. anticoagulants, antiplatelets, novel oral anticoagulants [NOAs], nonsteroidal anti-inflammatory drugs [NSAIDs], selective norepinephrine reuptake inhibitors [SNRI], or selective serotonin reuptake inhibitors [SSRIs] • Unable or unwilling to have a muscle biopsy • Weight has changed more than 5kg in past 3 months • Currently on a restrictive diet • Unable to attend the lab in Fitzroy, Melbourne for the 4 study visits for completion of study protocol

Outcome results

None listed

Source: ANZCTR · Data processed: Feb 4, 2026