Exogenous Ketone Supplements in Athletic Contexts: Past, Present, and Future.

The ketone bodies acetoacetate (AcAc) and ß-hydroxybutyrate (ßHB) have pleiotropic effects in multiple organs including brain, heart, and skeletal muscle by serving as an alternative substrate for energy provision, and by modulating inflammation, oxidative stress, catabolic processes, and gene expression. Of particular relevance to athletes are the metabolic actions of ketone bodies to alter substrate utilisation through attenuating glucose utilisation in peripheral tissues, anti-lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. There has been long-standing interest in the development of ingestible forms of ketone bodies that has recently resulted in the commercial availability of exogenous ketone supplements (EKS). These supplements in the form of ketone salts and ketone esters, in addition to ketogenic compounds such as 1,3-butanediol and medium chain triglycerides, facilitate an acute transient increase in circulating AcAc and ßHB concentrations, which has been termed 'acute nutritional ketosis' or 'intermittent exogenous ketosis'. Some studies have suggested beneficial effects of EKS to endurance performance, recovery, and overreaching, although many studies have failed to observe benefits of acute nutritional ketosis on performance or recovery. The present review explores the rationale and historical development of EKS, the mechanistic basis for their proposed effects, both positive and negative, and evidence to date for their effects on exercise performance and recovery outcomes before concluding with a discussion of methodological considerations and future directions in this field.

Effect of rapid weight loss incorporating hot salt water immersion on changes in body mass, blood markers, and indices of performance in male mixed martial arts athletes.

PURPOSE: To investigate the effects of rapid weight loss (RWL), incorporating comparison of hot water immersion (HWI) in fresh or salt water, on changes in body mass, blood markers, and indices of performance in mixed martial arts athletes. METHODS: In a crossover design comparing fresh water (FWB) to salt water (SWB; 5.0%wt/vol Epsom salt) bathing, 13 males performed 20 min of HWI (~ 40.3 °C) followed by 40 min wrapped in a heated blanket, twice in sequence (2 h total). Before bathing, ~ 26 to ~ 28 h of fluid and dietary restriction was undertaken, and ~ 24 to ~ 26 h of a high carbohydrate diet and rehydration was undertaken as recovery. RESULTS: During the entire RWL process, participants lost ~ 5.3% body mass. Body mass lost during the 2 h hot bath protocol was 2.17 ± 0.81 kg (~ 2.7% body mass) and 2.24 ± 0.64 kg (~ 2.8% body mass) for FWB and SWB, respectively (P = 0.647 between trials). Blood urea nitrogen, creatinine, sodium, chloride, hemoglobin, and hematocrit were increased (all P < 0.05), and plasma volume was decreased (~ 14%; P < 0.01), but did not differ between FWB and SWB, and were similar to baseline values after recovery. No indices of performance (e.g., countermovement jump, isometric strength, and functional threshold power) were impacted when RWL was followed by the recovery process. CONCLUSION: Under the conditions of this hot bath protocol, fluid loss was not augmented by the addition of ~ 5.0%wt/vol of Epsom salt during HWI, and RWL of ~ 5.3% body mass followed by > 24 h of recovery did not impact indices of performance.

No Effect of a Ketone Monoester on Markers of Stress and Performance in a Live-Burn Search and Rescue in Firefighters.

ABSTRACT: Waldman, HS, Bryant, AR, Shepherd, BD, Egan, B, and McAllister, MJ. No effect of a ketone monoester on markers of stress and performance in a live-burn search and rescue in firefighters. J Strength Cond Res 36(3): 763-771, 2022-Firefighters experience a range of stressors that impair performance and elevate the risk for developing cardiometabolic diseases. ß-Hydroxybutyrate (ßHB) has been shown to mitigate markers of oxidative stress and inflammation and serve as an alternative fuel with implications to physical performance. On 2 occasions in a double-blind, counterbalanced, and crossover design, 14 professional firefighters performed a live-burn, search and rescue (S&R) 30 minutes after ingestion of a ketone monoester (KME; 0.5 g·kg-1) or a placebo (PLA). Dependent variables collected before and after the S&R included salivary markers of stress and inflammation (cortisol, α-amylase, interleukin-1 beta, uric acid), perceptual markers (profile of mood state [POMS]), gastrointestinal distress (GI), rating of perceived exertion [RPE]), time to completion, and capillary blood measurement of ßHB and glucose. KME resulted in capillary ßHB concentrations of approximately 2.1-3.2 mM throughout the protocol. Capillary glucose concentrations were lower for the KME compared with PLA (∼7%) (interaction effect, p < 0.001). Salivary markers of stress, GI, and time to complete the S&R (∼10 minutes) did not differ between trials, although KME ingestion resulted in significantly higher RPE after the live-burn S&R (KME,6 ± 1; PLA, 4 ± 1). However, POMS data showed the KME also lowered subjective states of nervousness (KME, 0.0 ± 0.0; PLA, 0.6 ± 0.8) and anxiety (KME, 0.0 ± 0.0; PLA, 0.6 ± 0.7) before the S&R (all p < 0.05; large effect sizes). Compared with PLA, ingestion of a KME by firefighters did not mitigate the rise in various markers of salivary stress or impact physical performance during a live-burn S&R. However, differences in RPE and POMS variables were observed, suggesting a possible cognitive role for ßHB.

Interindividual variability in response to protein and fish oil supplementation in older adults: a randomized controlled trial.

BACKGROUND: Precision nutrition is highly topical. However, no studies have explored the interindividual variability in response to nutrition interventions for sarcopenia. The purpose of this study was to determine the magnitude of interindividual variability in response to two nutrition supplementation interventions for sarcopenia and metabolic health, after accounting for sources of variability not attributable to supplementation. METHODS: A 24 week, randomized, double-blind, placebo-controlled trial tested the impact of leucine-enriched protein (LEU-PRO), LEU-PRO plus long-chain n-3 PUFA (LEU-PRO+n-3) or control (CON) supplementation in older adults (n = 83, 71 ± 6 years) at risk of sarcopenia. To estimate the true interindividual variability in response to supplementation (free of the variability due to measurement error and within-subject variation), the standard deviation of individual responses (SDR ) was computed and compared with the minimally clinically important difference (MCID) for appendicular lean mass (ALM), leg strength, timed up-and-go (TUG), and serum triacylglycerol (TG) concentration. Clinically meaningful interindividual variability in response to supplementation was deemed to be present when the SDR positively exceeded the MCID. The probability that individual responses were clinically meaningful, and the phenotypic, dietary, and behavioural determinants of response to supplementation were examined. RESULTS: The SDR was below the MCID for ALM (LEU-PRO: -0.12 kg [90% CI: -0.38, 0.35], LEU-PRO+n-3: -0.32 kg [-0.45, 0.03], MCID: 0.21 kg), TUG (LEU-PRO: 0.58 s [0.18, 0.80], LEU-PRO+n-3: 0.73 s [0.41, 0.95], MCID: 0.9 s) and TG (LEU-PRO: -0.38 mmol/L [-0.80, 0.25], LEU-PRO+n-3: -0.44 mmol/L [-0.63, 0.06], MCID: 0.1 mmol/L), indicating no meaningful interindividual variability in response to either supplement. The SDR exceeded the MCID (19 Nm) for strength in response to LEU-PRO (25 Nm [-29, 45]) and LEU-PRO+n-3 (23 Nm [-29, 43]) supplementation but the effect was uncertain, evidenced by wide confidence intervals. In the next stage of analysis, similar proportions of participant responses were identified as very likely, likely, possibly, unlikely, and very unlikely to represent clinically meaningful improvements across the LEU-PRO, LEU-PRO+n-3, and CON groups (P > 0.05). Baseline LC n-3 PUFA status, habitual protein intake, and numerous other phenotypic and behavioural factors were not determinants of response to LEU-PRO or LEU-PRO+n-3 supplementation. CONCLUSIONS: Applying a novel, robust methodological approach to precision nutrition, we show that there was minimal interindividual variability in changes in ALM, muscle function, and TG in response to LEU-PRO and LEU-PRO+n-3 supplementation in older adults at risk of sarcopenia.

Self-Reported Prevalence, Magnitude, and Methods of Rapid Weight Loss in Male and Female Competitive Powerlifters.

ABSTRACT: Nolan, D, Lynch, AE, and Egan, B. Self-reported prevalence, magnitude, and methods of rapid weight loss in male and female competitive powerlifters. J Strength Cond Res 36(2): 405-410, 2022-Rapid weight loss (RWL) is common practice in weight category sports, but no empirical data exist documenting the weight-making practices of competitive strength athletes. This study investigated the self-reported prevalence, magnitude, and methods of RWL used by male and female powerlifters when preparing for competition. Competitive powerlifters (n = 321; M/F, 194/127) completed an anonymous online questionnaire previously validated for assessment of methods of RWL. Respondents were categorized by their federation's respective antidoping policy, weigh-in procedure, and degree of assistive equipment allowed, in addition to their use or not of RWL. Subgroup analyses were performed on the largest category of respondents (n = 200, M/F, 117/83; ≤2-hour weigh-in, drug-tested, "raw") based on sex, weight category, and competitive status. Prevalence of RWL was 85.8%, with an average RWL of 3.0 ± 1.9% body mass and an RWL score of 25.1 ± 7.4. Neither sex nor weight category influenced the RWL score, but in male athletes, a lower RWL score (22.7 ± 6.3) was reported in athletes in the lowest tertile of the Wilks score (p = 0.015). Frequencies of "always use" were reported as 54.0% for fluid restriction and 49.0% for water loading. Coaches (37.5%) and online resources (35.0%) were "very influential" on RWL practices in these athletes, while doctors (85.5%) and dieticians (63.0%) were reported to be "not influential." The prevalence of RWL is high in competitive powerlifting, and the methods used are akin to other weight category sports, but the reported RWL scores are lower than reported in combat sports with longer recovery periods after weigh-in.

Effects of a Long Chain n-3 Polyunsaturated Fatty Acid-rich Multi-ingredient Nutrition Supplement on Body Composition and Physical Function in Older Adults with Low Skeletal Muscle Mass.

Six months of supplementation with a multi-ingredient nutrition supplement was investigated in older adults with low skeletal muscle mass given the recently purported benefits of such approaches. Community-dwelling older adults (age, 74.9 ± 3.6 y; M/F, 18/19) participated in a double-blind, placebo-controlled, randomized trial involving daily consumption of either fruit juice placebo (PLA) or supplement (SUPP) in the form of a 200-mL carton of a juice-based emulsion of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) (3000 mg as 1500 mg docosahexaenoic acid and 1500 mg eicosapentaenoic acid), whey protein isolate (8 g), vitamin D3 (400 IU), and resveratrol (150 mg). Body composition, physical function, and circulating markers of metabolic health were assessed at baseline (PRE), and after 3 (MID) and 6 (POST) months of supplementation. Lean body mass (LBM) was unchanged in either group, but fat mass increased in SUPP by 1.41 (0.75, 2.07) kg at POST (+6.4%; p < .001; d = 0.20). Hand-grip strength was maintained in SUPP, but declined in PLA by 2.50 (0.81, 4.19) kg at POST (-6.8%; p = .002; d = 0.38). Short physical performance battery score was unchanged in PLA, but increased in SUPP by 1.13 (0.41, 1.84) above PRE at POST (p = .001; d = 0.47). Circulating markers of metabolic health were unchanged in response to the intervention in either PLA or SUPP. Long-term supplementation with an LC n-3 PUFA-rich multi-ingredient nutrition supplement demonstrates potential efficacy for improving physical function in older adults in the absence of exercise training and independent of a change in LBM.

Does supplementation with leucine-enriched protein alone and in combination with fish-oil-derived n-3 PUFA affect muscle mass, strength, physical performance, and muscle protein synthesis in well-nourished older adults? A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Leucine-enriched protein (LEU-PRO) and long-chain (LC) n-3 (ω-3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone. OBJECTIVE: The impact of LEU-PRO supplementation alone and combined with LC n-3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis (MyoPS) was investigated in older adults at risk of sarcopenia. METHODS: This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO (3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n-3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n-3; n = 38), or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28). RESULTS: Neither LEU-PRO nor LEU-PRO+n-3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: -7.1 Nm; 95% CI: -12.5, -1.8 Nm; P < 0.01) was lower postsupplementation in LEU-PRO+n-3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n-3 compared with CON postsupplementation (all P < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n-3 postsupplementation compared with CON (all P < 0.05). CONCLUSIONS: Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n-3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov as NCT03429491.

Nutritional Ketosis with Ketogenic Diets or Exogenous Ketones: Features, Convergence, and Divergence.

Athletes, clinicians, and practitioners are increasingly interested in the proposed performance and therapeutic benefits of nutritional ketosis (NK). NK is best operationally defined as a nutritionally induced metabolic state resulting in blood ß-hydroxybutyrate concentrations of ≥0.5 mM. Most tissues readily metabolize ketone bodies (KBs), and KBs in turn regulate metabolism and signaling in both a systemic and tissue-specific manner. During fasting, starvation, or ketogenic diets, endogenous synthesis of KBs is amplified resulting in a state of NK. Orally administered exogenous ketone supplements rapidly elevate circulating KBs and produce a similar, but far from identical, metabolic state. NK results in a number of convergent features regardless of endogenous or exogenous induction; however, important differences also are observed. The implications of NK across health, disease, and performance is rapidly becoming more evident, thus acknowledging the convergent and divergent features of NK is critical for fully understanding the potential utility of this metabolic state.

Acute ingestion of beetroot juice does not improve short-duration repeated sprint running performance in male team sport athletes.

The effects of acute ingestion of nitrate on short-duration repeated sprint performance (RSP) are unclear. This study investigated the effect of acute ingestion of beetroot juice on a test of RSP in team sport athletes. Sixteen male team sport athletes undertook four trials using a 40 m maximum shuttle run test (MST), which incorporates 10 × 40 m shuttle sprints with 30 s between the start of each sprint. Two familiarisation trials, followed by nitrate-rich beetroot juice (BR; ~6 mmol nitrate) and nitrate-depleted beetroot juice (PLA; ~0.0034 mmol nitrate) trials were completed in a randomised, double-blind manner. Ingestion of beetroot juice 3 h prior to exercise elevated plasma nitrate concentrations ~6-fold in BR (BR, 413 ± 56 µM; PLA, 69 ± 30 µM; P < 0.001). RSP, assessed by sprint performance decrement (Sdec; %), did not differ (P = 0.337) between BR (5.31 ± 2.49%) and PLA (5.71 ± 2.61%). There was no difference between trials for total sprint time (P = 0.806), fastest sprint (P = 0.341), slowest sprint (P = 0.787), or post-exercise blood lactate concentration (BR, 11.8 ± 2.5 mM; PLA, 12.2 ± 2.3 mM; P = 0.109). Therefore, acute ingestion of beetroot juice did not improve a test of short-duration RSP in team sport athletes.

Comparison of hot water immersion at 37.8°C with or without salt for rapid weight loss in mixed martial arts athletes.

Hot water immersion, known as a hot bath, is used by MMA athletes to produce rapid weight loss (RWL) by means of passive fluid loss. This study investigated the magnitude of body mass losses using a standardized hot bath protocol with or without the addition of salt. In a crossover design, eleven male MMA athletes (28.5 ± 4.6 y; 1.83 ± 0.07 m; 82.5 ± 9.1 kg) performed a 20-min immersion at 37.8°C followed by a 40-min wrap in a warm room. This bath and wrap was performed twice per visit. During one visit, only fresh water was used (FWB), and in the other visit, magnesium sulphate (1.6% wt/vol) was added to the bath (SWB). Prior to each visit, 24 h of carbohydrate, fibre, and fluid restriction was undertaken as part of the RWL protocol. Body mass losses induced by the hot bath protocols were 1.63 ± 0.75 kg and 1.60 ± 0.80 kg for FWB and SWB, respectively, and equivalent to ~2.1% body mass. Under the conditions employed, the magnitude of body mass loss in SWB was similar to FWB. However, further research should explore bathing in a temperature that is consistent with that habitually used by fighters, and/or higher concentrations of salt.

No Benefit of Ingestion of a Ketone Monoester Supplement on 10-km Running Performance.

PURPOSE: Preexercise ingestion of exogenous ketones alters the metabolic response to exercise, but effects on exercise performance have been equivocal. METHODS: On two occasions in a double-blind, randomized crossover design, eight endurance-trained runners performed 1 h of submaximal exercise at approximately 65% V˙O2max immediately followed by a 10-km self-paced time trial (TT) on a motorized treadmill. An 8% carbohydrate-electrolyte solution was consumed before and during exercise, either alone (CHO + PLA), or with 573 mg·kg of a ketone monoester supplement (CHO + KME). Expired air, HR, and RPE were monitored during submaximal exercise. Serial venous blood samples were assayed for plasma glucose, lactate, and ß-hydroxybutyrate concentrations. RESULTS: CHO + KME produced plasma ß-hydroxybutyrate concentrations of approximately 1.0 to 1.3 mM during exercise (P < 0.001), but plasma glucose and lactate concentrations were similar during exercise in both trials. V˙O2, running economy, respiratory exchange ratio, HR, and RPE were also similar between trials. Performance in the 10-km TT was not different (P = 0.483) between CHO + KME (mean, 2402 s; 95% confidence interval, 2204-2600 s) and CHO + PLA (mean, 2422 s; 95% confidence interval, 2217-2628 s). Cognitive performance, measured by reaction time and a multitasking test, did not differ between trials. CONCLUSIONS: Compared with carbohydrate alone, coingestion of KME by endurance-trained athletes elevated plasma ß-hydroxybutyrate concentrations, but did not improve 10-km running TT or cognitive performance.

The effects of a combined bodyweight-based and elastic bands resistance training, with or without protein supplementation, on muscle mass, signaling and heat shock response in healthy older people.

This investigation sought to determine the effects of twelve weeks of resistance exercise training in addition to protein supplementation on body composition, markers of muscle atrophy/hypertrophy and heat shock response (HSR) in healthy older adults. Thirty-eight healthy sedentary participants (M/F, 18/20; age, 63.5 ±â€¯4.4 y) were randomly assigned to four groups: I) PLACEBO: no training, receiving placebo sachets; II) NUTRITION: no training, receiving protein supplementation sachets; III) EXERCISE PLACEBO: training, placebo sachets and IV) EXERCISE NUTRITION: training, receiving protein sachets. The resistance training (using bodyweight and elastic bands) consisted of 45 min supervised training sessions, 3×/week. Participants from both exercise groups increased their total lean body mass (from 48.4 ±â€¯8.7 to 49.2 ±â€¯8.7 kg and from 44.9 ±â€¯7.8 to 45.9 ±â€¯8.1 kg, average of gain ~0.8 and 1 kg, placebo and nutrition respectively) and improved results in physical tests. Exercise nutrition group also reduced their body fat (from 34.8 ±â€¯7.3 to 32.9 ±â€¯7.4%), increased the expression of proteins/gene involved on the HSR, S6 and eEF2, while FOXO3 and Murf1 were reduced. Expression of MHC-I was reduced in both exercise groups while MHC-IIa increased, with no effect of protein supplementation alone. Body-weight and elastic bands based resistance exercise prompted, in healthy older people, improvements in body composition and muscle function. When protein supplementation was added to the people engaged in resistance training, improvements in fat mass and changes in skeletal muscle signaling were detected, favoring protein synthesis pathways and the protective heat shock response.

Intermittent Running and Cognitive Performance after Ketone Ester Ingestion.

PURPOSE: Ingestion of exogenous ketones alters the metabolic response to exercise and may improve exercise performance, but it has not been explored in variable-intensity team sport activity, or for effects on cognitive function. METHODS: On two occasions in a double-blind, randomized crossover design, 11 male team sport athletes performed the Loughborough Intermittent Shuttle Test (part A, 5 × 15-min intermittent running; part B, shuttle run to exhaustion), with a cognitive test battery before and after. A 6.4% carbohydrate-electrolyte solution was consumed before and during exercise either alone (PLA) or with 750 mg·kg of a ketone ester (KE) supplement. Heart rate, RPE, and 15-m sprint times were recorded throughout, and serial venous blood samples were assayed for plasma glucose, lactate, and ß-hydroxybutyrate. RESULTS: KE resulted in plasma ß-hydroxybutyrate concentrations of ~1.5 to 2.6 mM during exercise (P < 0.001). Plasma glucose and lactate concentrations were lower during KE compared with PLA (moderate-to-large effect sizes). Heart rate, RPE, and 15-m sprint times did not differ between trials. Run time to exhaustion was not different (P = 0.126, d = 0.45) between PLA (mean = 268 s, 95% confidence interval [CI] = 199-336 s) and KE (mean = 229 s, 95% CI = 178-280 s). Incorrect responses in a multitasking test increased from pre- to postexercise in PLA (mean = 1.8, 95% CI = -0.6 to 4.1) but not in KE (mean = 0.0, 95% CI = -1.8 to 1.8) (P = 0.017, d = 0.70). CONCLUSION: Compared with carbohydrate alone, coingestion of a KE by team sport athletes attenuated the rise in plasma lactate concentrations but did not improve shuttle run time to exhaustion or 15-m sprint times during intermittent running. An attenuation of the decline in executive function after exhausting exercise suggests a cognitive benefit after KE ingestion.

Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions.

Creatine monohydrate represents one of the largest sports supplement markets. Enhancing creatine (CRE) stability in aqueous solutions, such as with microencapsulation, represents innovation potential. Ten physically active male volunteers were randomly assigned in a double-blind design to either placebo (PLA) (3-g maltodextrin; n = 5) or microencapsulated CRE (3-g creatine monohydrate; n = 5) conditions. Experimental conditions involved ingestion of the samples in a 70-mL ready-to-drink format. CRE was delivered in a novel microencapsulation matrix material consisting entirely of hydrolyzed milk protein. Three hours after ingestion, plasma creatine concentrations were unchanged during PLA, and averaged ∼45 µM. During CRE, plasma creatine concentration peaked after 30 min at 101.6 ± 14.9 µM (p < 0.05), representing a 2.3-fold increase over PLA. Thereafter, plasma creatine concentration gradually trended downwards but remained significantly elevated (∼50% above resting levels) 3 hr after ingestion. These results demonstrate that the microencapsulated form of creatine monohydrate reported herein remains bioavailable when delivered in aqueous conditions, and has potential utility in ready-to-drink formulations for creatine supplementation.

Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation.

Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and ß-hydroxybutyrate (ßHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post-exercise recovery period, and the ability to utilise ketone bodies is higher in exercise-trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti-lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with ßHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of ßHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes.