Content uploaded by Chiel Poffé
Author content
All content in this area was uploaded by Chiel Poffé on Aug 03, 2020
Content may be subject to copyright.
A preview of the PDF is not available
Bicarbonate Unlocks the Ergogenic Action of Ketone Monoester Intake in Endurance Exercise
Abstract and Figures
Purpose:
We recently reported that oral ketone ester (KE) intake before and during the initial 30 min of a ~3h 15 min simulated cycling race (RACE) transiently decreased blood pH and bicarbonate without affecting maximal performance in the final quarter of the event. We hypothesized that acid-base disturbances due to KE overrules the ergogenic potential of exogenous ketosis in endurance exercise.
Methods:
Nine well-trained male cyclists participated in a similar RACE consisting of 3h submaximal intermittent cycling (IMT180') followed by a 15-min time-trial (TT15') preceding an all-out sprint at 175% of lactate threshold (SPRINT). In a randomized cross-over design participants received either i) 65g ketone ester (KE), ii) 300 mg/kg body weight NaHCO3 (BIC), iii) KE+BIC or iv) a control drink (CON), together with consistent 60g per h carbohydrate intake.
Results:
KE ingestion transiently elevated blood D-ß-hydroxybutyrate to ~2-3 mM during the initial 2 hours of RACE (p< 0.001 vs. CON). In KE, blood pH concomitantly dropped from 7.43 to 7.36 whilst bicarbonate decreased from 25.5 to 20.5 mM (both p<0.001 vs. CON). Additional BIC resulted in 0.5 to 0.8 mM higher blood D-ß-hydroxybutyrate during the first half of IMT180' (p < 0.05 vs. KE) and increased blood bicarbonate to 31.1±1.8 mM and blood pH to 7.51±0.03 by the end of IMT180' (p<0.001 vs. KE). Mean power output during TT15' was similar between KE, BIC and CON at ~255 W, but was 5% higher in KE+BIC (p=0.02 vs. CON). Time-to-exhaustion in the sprint was similar between all conditions at ~60s (p=0.88). Gastrointestinal symptoms were similar between groups.
Discussion:
Co-ingestion of oral bicarbonate and KE enhances high-intensity performance at the end of an endurance exercise event without causing gastrointestinal distress.
Figures - uploaded by Chiel Poffé
Author content
All figure content in this area was uploaded by Chiel Poffé
Content may be subject to copyright.
... Twelve studies anchored the fractional (%) intensity of the pre-load protocol based on peak power output (PPO) (Palmer et al. 1997;Baume et al. 2008;Christensen et al. 2024;Guillochon and Rowlands 2017;Helge et al. 2023;O'Brien et al. 2023;Rauch et al. 1995;Rauch et al. 1995;Rowlands and Hopkins 2002;Slattery et al. 2014;Stanley et al. 2013;Vaile et al. 2008), 13 based on V O 2max/peak (Cureton et al. 2007;Ganio et al. 2011Ganio et al. , 2010Glazier et al. 2004;Goulet et al. 2008;Hargreaves et al. 1984;Hickner et al. 2010;Murray et al. 1991;Paul et al. 2001;Salvador et al. 1985;Sherman et al. 1989;Stebbins et al. 2014;Talanian and Spriet 2016) whilst 13 studies anchored exercise intensity based on physiological variables linked to exercise intensity domains (moderate, heavy, severe, extreme). Specifically, nine studies used lactate outcomes obtained during screening assessments to quantify % exercise intensity, including absolute lactate values (Vandebuerie et al. 1998), maximal lactate steady state (Thienen et al. 2009), traditional lactate thresholds 1 (Poffé et al. 2021a(Poffé et al. , 1985(Poffé et al. , 2021bRobberechts et al. 1985;Dalle et al. 2021) and2 (Schuylenbergh et al. 2005) or estimation of maximal lactate steady state using D max mathematical modelling (Cramp et al. 2004). Further methods included fractions of ventilatory thresholds (Kremenic et al. 2009;Glace et al. 2019Glace et al. , 2013 and critical power (CP) (Spragg et al. 2023). ...
... In the current search, protocols that used exercise domains as anchors, limitations exist. Some protocols had their intensity below LT 1 for the full pre-load (Poffé et al. 2021a(Poffé et al. , 1985(Poffé et al. , 2021bRobberechts et al. 1985;Dalle et al. 2021), which might not be representative of cycling race intensity distribution (Sanders and Heijboer 2019). Others used the boundary between the heavy and severe domain (LT 2 , CP or maximum lactate steady state) as anchor, but it was unclear whether intensities ever dropped into the moderate domain (Thienen et al. 2009;Schuylenbergh et al. 2005;Spragg et al. 2023). ...
... The types of performance test following the pre-load were time-to-exhaustion (Guillochon and Rowlands 2017;Helge et al. 2023;Goulet et al. 2008;Hargreaves et al. 1984;Hickner et al. 2010;Stebbins et al. 2014;Schuylenbergh et al. 2005), time trials with fixed amount of work to be performed (i.e. distance) (Palmer et al. 1997;Baume et al. 2008;O'Brien et al. 2023;Rowlands and Hopkins 2002;Murray et al. 1991;Kremenic et al. 2009;Glace et al. 2019Glace et al. , 2013Burke et al. 1985;Schabort et al. 1998;Hunter et al. 2002;Macdermid et al. 2012;Levin et al. 2014;Abbiss et al. 2010;St Clair Gibson et al. 2001;Perim et al. 2022), work (Christensen et al. 2024;Glazier et al. 2004;Paul et al. 2001;Salvador et al. 1985;Sherman et al. 1989;Talanian and Spriet 2016) or time (Rauch et al. 1995(Rauch et al. , 2005Slattery et al. 2014;Stanley et al. 2013;Vaile et al. 2008;Cureton et al. 2007;Ganio et al. 2011Ganio et al. , 2010, maximal sprints (Cramp et al. 2004), multiple fixed time all-out tests for CP determination (i.e. 3 min and 12 min) (Spragg et al. 2023) or a combination of multiple performance tests (Vandebuerie et al. 1998;Thienen et al. 2009;Poffé et al. 2021aPoffé et al. , 1985Poffé et al. , 2021bRobberechts et al. 1985;Dalle et al. 2021;Ørtenblad et al. 2024). Clearly on many occasions, the winner of a road race is decided by a final effort, hence this review evaluated the type of performance tests used in the simulations. ...
Physiological resilience or durability is now recognised as a determinant of endurance performance such as road cycling. Reliable, ecologically valid and standardised performance tests in laboratory-based cycling protocols have to be established to investigate mechanisms underpinning, and interventions improving durability. This review aims to provide an overview of available race simulation protocols in the literature and examines its rigour around themes that influence durability including (i) exercise intensity anchoring and (ii) carbohydrate intake whilst also (iii) inspecting reliability and justification of the developed protocols. Using a systematic search approach, 48 articles were identified that met our criteria as a cycling race simulation. Most protocols presented limitations to be recommended as exercise test to investigate durability, such as not appropriately addressing the influence of exercise intensity domains by anchoring exercise intensity as % peak power or % O2max. Ten articles provided reliability data, but only one articles under the appropriate conditions. Most studies sufficiently controlled nutrition during trials but not in the days leading to the trials or just before the trials. Thus, there is a paucity in protocols that combine justification and reliability with optimal nutritional support and mimic the true demands of a road-cycling race. This review lists an overview of protocols that researchers could use with caution to select a protocol for future experiments, but encourages further development of improved protocols, including utilisation of virtual software applications.
... In preclinical models, ketone bodies and KEs attenuate muscle atrophy through anticatabolic signaling activities [18,19], improve heart function in age-related heart failure through direct energetic support [20,21], and promote healthy function of T cell subpopulations [22,23]. This hypothesis is further supported by demonstrated effects of KEs on blood glucose control [24][25][26][27], physical [28][29][30], cognitive [31][32][33], immune [34], and cardiovascular [33,35] function in younger adult populations. These examples support our central hypothesis that ketone bodies delivered through KEs may ameliorate the frailty syndrome through multi-system energetic and signaling activities that improve metabolic and immune function. ...
Background
Frailty is a geriatric syndrome characterized by chronic inflammation and metabolic insufficiency that creates vulnerability to poor outcomes with aging. We hypothesize that interventions which target common underlying mechanism of aging could ameliorate frailty. Ketone bodies are metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on inflammatory and metabolic aging pathways in laboratory animal models. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. Our long-term goal is to examine if KEs modulate aging biology mechanisms and clinical outcomes relevant to frailty in older adults.
Objectives
The primary objective of this randomized, placebo-controlled, double-blinded, parallel-group, pilot trial is to determine tolerability of 12-weeks of KE ingestion in a broad population of older adults (≥ 65 years). Secondary outcomes include safety and acute blood ketone kinetics. Exploratory outcomes include physical function, cognitive function, quality of life, aging biomarkers and inflammatory measures.
Methods
Community-dwelling adults who are independent in activities of daily living, with no unstable acute medical conditions (n = 30) will be recruited. The study intervention is a KE or a taste, appearance, and calorie matched placebo beverage. Initially, acute 4-hour ketone kinetics after 12.5g or 25g of KE consumption will be assessed. After collection of baseline safety, functional, and biological measurements, subjects will randomly be allocated to consume KE 25g or placebo once daily for 12-weeks. Questionnaires will assess tolerability daily for 2-weeks, and then via phone interview at bi-monthly intervals. Safety assessments will be repeated at week 4. All measures will be repeated at week 12.
Conclusion
This study will evaluate feasibility, tolerability, and safety of KE consumption in older adults and provide exploratory data across a range of aging-related endpoints. This data will inform design of larger trials to rigorously test KE effects on aging mechanisms and clinical outcomes relevant to frailty.
... 44 Alternatively, it was suspected that a transient decrease in blood pH caused by acute ketone supplementation may cancel out the potential advantages of ketone supplements. 40,41 However, change in plasma pH was not measured in the studies giving acute supplementation. 20,[42][43][44]50 Aerobic performance could also be affected negatively by GI discomfort after consuming ketone supplements. ...
Context:
Ketogenic diets and ketone supplements have gained popularity among endurance runners given their purported effects: potentially delaying the onset of fatigue by enabling the increased utilization of the body's fat reserve or external ketone bodies during prolonged running.
Objective:
This systematic review was conducted to evaluate the effects of ketogenic diets (>60% fat and <10% carbohydrates/<50 g carbohydrates per day) or ketone supplements (ketone esters or ketone salts, medium-chain triglycerides or 1,3-butadiol) on the aerobic performance of endurance runners.
Data sources:
A systematic search was conducted in PubMed, Web of Science, Pro Quest, and Science Direct for publications up to October 2023.
Study selection:
Human studies on the effects of ketogenic diets or ketone supplements on the aerobic performance of adult endurance runners were included after independent screening by 2 reviewers.
Study design:
Systematic review.
Level of evidence:
Level 3.
Data extraction:
Primary outcomes were markers of aerobic performance (maximal oxygen uptake [VO2max], race time, time to exhaustion and rate of perceived exertion).
Results:
VO2max was assessed by incremental test to exhaustion. Endurance performance was assessed by time trials, 180-minute running trials, or run-to-exhaustion trials; 5 studies on ketogenic diets and 7 studies on ketone supplements involving a total of 132 endurance runners were included. Despite the heterogeneity in study design and protocol, none reported benefits of ketogenic diets or ketone supplements on selected markers of aerobic performance compared with controls. Reduction in bodyweight and fat while preserving lean mass and improved glycemic control were reported in some included studies on ketogenic diets.
Conclusion:
This review did not identify any significant advantages or disadvantages of ketogenic diets or ketone supplements for the aerobic performance of endurance runners. Further trials with larger sample sizes, more gender-balanced participants, longer ketogenic diet interventions, and follow-up on metabolic health are warranted.
Sporcu performansını artırmak amacıyla kullanılan besin takviyeleri teknolojinin ilerlemesiyle birlikte bu takviyelerin çeşitliliğinin ve erişilebilirliğinin artması nedeniyle geçmişe kıyasla daha fazla ön plana çıkmıştır. Bu bağlamda çalışmada besin takviyelerinin sporcu performansını hangi yönlerden etkilediği ve sağlıklı kullanım dozajlarının nasıl olması gerektiği güncel literatür yardımıyla açıklanmaya çalışılmıştır. Araştırmada öncelikle besin takviyeleri hakkında genel bir bilgi verilerek besin takviyeleri tanıtılmış sonrasında her bir besin takviyesinin özelliklerine uygun olarak sporcu performansı üzerindeki olası etkilerinden bahsedilmiştir. Ayrıca besin takviyelerinin kullanım dozajları konusunda son dokuz yıldaki literatürde var olan öneriler çalışma içinde sunulmuştur. Bir beslenme uzmanı yardımı alınarak doğru bir şekilde tüketilen besin takviyeleri sporcu performansını farklı etki mekanizmaları yoluyla olumlu etkilemektedir. Sporcuların bir kısmı için diyetlerini yeniden planlayarak besin takviyelerine olan ihtiyaç karşılanabilirken, diğer bir kısmı için performans gösterdikleri spor dalı nedeniyle diyetle alınan miktar yeterli olmayıp uzman kontrolünde besin takviyelerini diyetlerine ek olarak almaları gerekmektedir. Bu nedenle sporcuların besin takviyelerinin yan etkilerinden dolayı sağlık açısından zarar görmemeleri ve en üst düzeyde fayda elde edebilmeleri için sporcunun fiziksel durumuna, spor dalına ve diyetine uygun olacak şekilde besin takviyesi alımının bilimsel çalışmalardaki öneriler doğrultusunda bireye özgü olarak planlanması büyük önem taşımaktadır.
Background Sleeping at (simulated) altitude is highly common in athletes as an integral part of altitude training camps or sport competitions. However, it is also often feared due to proclaimed negative effects on sleep quality, thereby potentially hampering exercise recovery and next-day exercise performance. We recently showed that ketone ester (KE) ingestion beneficially impacted sleep following strenuous, late evening exercise in normoxia, and alleviated hypoxemia. Therefore, we hypothesized that KE ingestion may be an effective strategy to attenuate hypox(em)ia-induced sleep dysregulations.Methods Eleven healthy, male participants completed three experimental sessions including normoxic training and subsequent sleep in normoxia or at a simulated altitude of 3,000m while receiving either KE or placebo post-exercise and pre-sleep. Sleep was evaluated using polysomnography, while next-day exercise performance was assessed through a 30-min all-out time trial (TT30’). Physiological measurements included oxygen status, heart rate variability, ventilatory parameters, blood acid-base balance and capillary blood gases.Results Hypoxia caused a ∼3% drop in sleep efficiency, established through a doubled wakefulness after sleep onset and a ∼22% reduction in slow wave sleep. KE ingestion alleviated the gradual drop in SpO2 throughout the first part of the night, but did not alter hypoxia-induced sleep dysregulations. Neither KE, nor nocturnal hypoxia affected TT30’ performance, but nocturnal hypoxia hampered heart rate recovery following TT30’.Conclusion We observed that sleeping at 3,000m altitude already impairs sleep efficiency. Although this hypoxia-induced sleep disruption was too subtle to limit exercise performance, we for the first time indicate that sleeping at altitude impairs next-day exercise recovery. KE alleviated nocturnal hypoxemia whenever SpO2 values dropped below ∼85%, but this did not translate into improved sleep or next-day exercise performance.
Recent evidence suggests that ketone bodies have therapeutic potential in many cardiovascular diseases including heart failure (HF). Accordingly, this has led to multiple clinical trials that use ketone esters (KEs) to treat HF patients highlighting the importance of this ketone therapy. KEs, specifically ketone monoesters, are synthetic compounds which, when consumed, are de-esterified into two β-hydroxybutyrate (βOHB) molecules and increase the circulating βOHB concentration. While many studies have primarily focused on the cardiac benefits of ketone therapy in HF, ketones can have numerous favourable effects in other organs such as the vasculature and skeletal muscle. Importantly, vascular and skeletal muscle dysfunction are also heavily implicated in the reduced exercise tolerance, the hallmark feature in HF with reduced ejection fraction and preserved ejection fraction, suggesting that some of the benefits observed in HF in response to ketone therapy may involve these non-cardiac pathways. Thus, we review the evidence suggesting how ketone therapy may be beneficial in improving cardiovascular and skeletal muscle function in HF and identify various potential mechanisms that may be important in the beneficial non-cardiac effects of ketones in HF.
Disruptions to acid-base are observed in extreme environments as well as respiratory and metabolic diseases. Exogenous ketone supplements (EKS) have been proposed to mitigate these processes and provide therapeutic benefits by altering acid-base balance and metabolism, but direct comparisons of various forms of EKS is lacking. Twenty healthy participants (M/F: 10/10; age: 20.6±2.0 y, height: 1.72±0.08 m, body mass: 67.9±10.2 kg) participated in a single-blind, randomized crossover design comparing ingestion of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME), KME+sodium bicarbonate (KME+BIC), an R-βHB ketone salt (KS), and a flavor-matched placebo. Acid-base balance, blood R-βHB, glucose and lactate concentrations, blood gases, respiratory gas exchange, autonomic function, and cognitive performance were assessed at baseline, and various time points for up to 120 min after ingestion. Compared to PLA, blood R-βHB concentration were elevated in each EKS condition (~2 to 4 mM; P<0.01) and blood glucose concentration were lower. Blood pH was lower in KME (-0.07 units), and higher in KS and KME+BIC (+0.05 units), compared to PLA (all P<0.05). Heart rate was elevated, and autonomic function was altered in KME+BIC. There were no differences between conditions for blood gases, respiratory gas exchange, blood pressure or cognitive performance. Exploratory analyses of between-sex differences demonstrated males and females responded similarly across all outcome measures. Altering the acid load of EKS modulated the response of blood R-βHB and glucose concentrations, but had only modest effects on other outcomes measures at rest in young healthy adults, with no differences observed between sexes.
A high-fat, low-carbohydrate, ketogenic diet has already appealed to athletes for a long time due to its purported ability to improve exercise performance and post-exercise recovery. The availability of ketone supplements has further sparked such interest. The review therefore focuses on the potential beneficial impact of exogenous and endogenous ketosis in the context of ultra-endurance exercise.
Background: Acute mountain sickness (AMS) represents a considerable issue for individuals sojourning to high altitudes with systemic hypoxemia known to be intimately involved in its development. Based on recent evidence that ketone ester (KE) intake attenuates hypoxemia, we investigated whether exogenous ketosis might mitigate AMS development and to identify underlying physiological mechanisms. Methods: Fourteen healthy, male participants were enrolled in two 29h protocols (simulated altitude of 4,000-4,500m) receiving either KE or a placebo (CON) at regular timepoints throughout the protocol in a randomized, crossover manner. Physiological responses were characterized after 15min and 4h in hypoxia, and the protocol was terminated prematurely upon development of severe AMS (Lake Louise Score ≥ 10). Results: KE ingestion induced a consistent diurnal ketosis ([ßHB] of ~3 mM), whereas blood [ßHB] remained low (<0.6 mM) in CON. Each participant tolerated the protocol equally long or longer (n=6 or n=8, resp.) in KE. Protocol duration increased by 32% on average with KE, and doubled upon KE for severe AMS-developing participants (n=9). Relative to CON, KE induced a mild metabolic acidosis, hyperventilation, and relative sympathetic dominance. KE also inhibited the progressive hypoxemia that was observed between 15min and 4h in hypoxia in CON, while concomitantly increasing cerebral oxygenation and capillary pO 2 within this timeframe despite a KE-induced reduction in cerebral oxygen supply. Conclusions: These data indicate that exogenous ketosis attenuates AMS development. The key underlying mechanisms include improved arterial and cerebral oxygenation, in combination with lowered cerebral blood flow and oxygen delivery, and increased sympathetic dominance.
Acute ingestion of exogenous ketone supplements in the form of a (R)‐3‐hydroxybutyl (R)‐3‐hydroxybutyrate (R‐BD R‐βHB) ketone monoester (KME) can attenuate declines in oxygen availability during hypoxic exposure and might impact cognitive performance at rest and in response to moderate‐intensity exercise. In a single‐blind randomized crossover design, 16 males performed assessments of cognitive performance before and during hypoxic exposure with moderate exercise [2 × 20 min weighted ruck (∼22 kg) at 3.2 km/h at 10% incline] in a normobaric altitude chamber (4572 m, 11.8% O2). The R‐BD R‐βHB KME (573 mg/kg) or a calorie‐ and taste‐matched placebo (∼50 g maltodextrin) were co‐ingested with 40 g of dextrose before exposure to hypoxia. The R‐βHB concentrations were rapidly elevated and sustained (>3 mM; P < 0.001) by KME. The decline in oxygen saturation during hypoxic exposure was attenuated in KME conditions by 2.4%–4.2% (P < 0.05) compared with placebo. Outcomes of cognitive performance tasks, in the form of the Defense Automated Neurobehavioral Assessment (DANA) code substitution task, the Stroop color and word task, and a shooting simulation, did not differ between trials before and during hypoxic exposure. These data suggest that the acute exogenous ketosis induced by KME ingestion can attenuate declining blood oxygen saturation during acute hypoxic exposure both at rest and during moderate‐intensity exercise, but this did not translate into differences in cognitive performance before or after exercise in the conditions investigated.
Available evidence indicates that ketone bodies inhibit glycolysis in contracting muscles. Therefore, we investigated whether acute exogenous ketosis by oral ketone ester (KE) intake early in a simulated cycling race, can induce transient glycogen sparing by glycolytic inhibition thereby increasing glycogen availability in the final phase of the event. In a randomized cross-over design, 12 highly-trained male cyclists completed a simulated cycling race (RACE), which consisted of 3h intermittent cycling (IMT 180' ), a 15-min time-trial (TT 15' ) and a maximal sprint (SPRINT). During RACE subjects received 60g carbohydrates per h combined with three boluses (25-20-20g) (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) or a control drink (CON) at 60 and 20 min before, and at 30 min during RACE. KE intake transiently increased blood D-ß-hydroxybutyrate to ~3 mM (range: 2.6-5.2 mM) during the first half of RACE (p<0.001 vs. CON). Blood pH concomitantly decreased from ~7.42 to 7.36 (range: 7.29-7.40), whilst bicarbonate dropped from 26.0 to 21.6 mM (range: 20.1-23.7) (both p<0.001 vs. CON) . Net muscle glycogen breakdown during IMT 180' (KE: -78±30 (SD); CON: -60±22 mmol/kg ww, p=0.08) and TT 15' (KE: -9±18; CON: -18±18 mmol/kg ww, p=0.35) was similar between KE and CON. Accordingly, mean power output during TT 15' (KE: 273±38; CON: 272±37 W, p=0.83) and time-to-exhaustion in the SPRINT (KE: 59±16; CON: 58±17 s, p=0.66) were similar between conditions. In conclusion, KE intake during a simulated cycling race does not cause glycogen sparing, neither does it affect all-out performance in the final stage of a simulated race.
Ingesting exogenous ketone bodies has been touted as producing ergogenic effects by altering substrate metabolism; however, research findings from recent studies appear inconsistent. This systematic review aimed to aggregate data from the current literature to examine the impact of consuming ketone supplements on enhancing physical performance. A systematic search was performed for randomized controlled trials that measured physical performance outcomes in response to ingesting exogenous ketone supplements compared with a control (nutritive or non-nutritive) in humans. A total of 161 articles were screened. Data were extracted from 10 eligible studies (112 participants; 109 men, 3 women ) containing 16 performance outcomes [lower-body power (n = 8) and endurance performance (n = 8)]. Ketone supplements were grouped as ketone esters (n = 8) or ketone salts/precursors (n = 8). Of the 16 performance outcomes identified by the systematic review, 3 reported positive, 10 reported null, and 3 reported negative effects of ketone supplementation on physical performance compared with controls. Heterogeneity was detected for lower-body power ( Q = 40, I2 = 83%, P < 0.01) and endurance performance (Q = 95, I2 = 93%, P < 0.01) between studies. Similarly high levels of heterogeneity were detected in studies providing ketone esters (Q = 111, I2 = 93%, P < 0.01), and to a lesser extent studies with ketone salts/precursors (Q = 25, I2 = 72%, P < 0.01). Heterogeneity across studies makes it difficult to conclude any benefit or detriment to consuming ketone supplements on physical performance. This systematic review discusses factors within individual studies that may contribute to discordant outcomes across investigations to elucidate if there is sufficient evidence to warrant recommendation of consuming exogenous ketone supplements to enhance physical performance.
Purpose Pre-exercise 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 ~65% VO2max immediately followed by a 10-km self-paced 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-1 of a ketone monoester supplement (CHO+KME). Expired air, heart rate (HR), and rating of perceived exertion (RPE) were monitored during submaximal exercise. Serial venous blood samples were assayed for plasma glucose, lactate and β-hydroxybutyrate concentrations.
Results CHO+KME produced plasma β-hydroxybutyrate concentrations of ~1.0 to 1.3 mM during exercise (P < 0.001), but plasma glucose and lactate concentrations were similar during exercise in both trials. VO2, 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 [CI] = 2204, 2600 s) and CHO+PLA (mean = 2422 s; 95% CI = 2217, 2628 s). Cognitive performance, measured by reaction time and a multi-tasking test, did not differ between trials.
Conclusion Compared with carbohydrate alone, co-ingestion of KME by endurance-trained athletes elevated plasma β-hydroxybutyrate concentrations, but did not improve 10-km running TT or cognitive performance.
Key points
Overload training is required for sustained performance gain in athletes (functional overreaching). However, excess overload may result in a catabolic state which causes performance decrements for weeks (non‐functional overreaching) up to months (overtraining).
Blood ketone bodies can attenuate training‐ or fasting‐induced catabolic events. Therefore, we investigated whether increasing blood ketone levels by oral ketone ester (KE) intake can protect against endurance training‐induced overreaching.
We show for the first time that KE intake following exercise markedly blunts the development of physiological symptoms indicating overreaching, and at the same time significantly enhances endurance exercise performance.
We provide preliminary data to indicate that growth differentiation factor 15 (GDF15) may be a relevant hormonal marker to diagnose the development of overtraining.
Collectively, our data indicate that ketone ester intake is a potent nutritional strategy to prevent the development of non‐functional overreaching and to stimulate endurance exercise performance.
Abstract
It is well known that elevated blood ketones attenuate net muscle protein breakdown, as well as negate catabolic events, during energy deficit. Therefore, we hypothesized that oral ketones can blunt endurance training‐induced overreaching. Fit male subjects participated in two daily training sessions (3 weeks, 6 days/week) while receiving either a ketone ester (KE, n = 9) or a control drink (CON, n = 9) following each session. Sustainable training load in week 3 as well as power output in the final 30 min of a 2‐h standardized endurance session were 15% higher in KE than in CON (both P < 0.05). KE inhibited the training‐induced increase in nocturnal adrenaline (P < 0.01) and noradrenaline (P < 0.01) excretion, as well as blunted the decrease in resting (CON: −6 ± 2 bpm; KE: +2 ± 3 bpm, P < 0.05), submaximal (CON: −15 ± 3 bpm; KE: −7 ± 2 bpm, P < 0.05) and maximal (CON: −17 ± 2 bpm; KE: −10 ± 2 bpm, P < 0.01) heart rate. Energy balance during the training period spontaneously turned negative in CON (−2135 kJ/day), but not in KE (+198 kJ/day). The training consistently increased growth differentiation factor 15 (GDF15), but ∼2‐fold more in CON than in KE (P < 0.05). In addition, delta GDF15 correlated with the training‐induced drop in maximal heart rate (r = 0.60, P < 0.001) and decrease in osteocalcin (r = 0.61, P < 0.01). Other measurements such as blood ACTH, cortisol, IL‐6, leptin, ghrelin and lymphocyte count, and muscle glycogen content did not differentiate KE from CON. In conclusion, KE during strenuous endurance training attenuates the development of overreaching. We also identify GDF15 as a possible marker of overtraining.
Purpose: Ketosis, achieved through ingestion of ketone esters, may influence endurance exercise capacity by altering substrate metabolism. However, the effects of ketone consumption on acid-base status and subsequent metabolic and respiratory compensations are poorly described.
Methods: Twelve athletically trained individuals completed an incremental bicycle ergometer exercise test to exhaustion following the consumption of either a ketone ester [(R)-3-hydroxybutyrate-(R)-1,3-butanediol] or a taste-matched control drink (bitter flavoured water) in a blinded, cross-over study. Respiratory gases and arterialised blood gas samples were taken at rest and at regular intervals during exercise.
Results: Ketone ester consumption increased blood D-β-hydroxybutyrate concentration from 0.2 to 3.7 mM/L (p < 0.01), causing significant falls versus control in blood pH to 7.37 and bicarbonate to 18.5 mM/L before exercise. To compensate for ketoacidosis, minute ventilation was modestly increased (p < 0.05) with non-linearity in the ventilatory response to exercise (ventilatory threshold) occurring at a 22 W lower workload (p < 0.05). Blood pH and bicarbonate concentrations were the same at maximal exercise intensities. There was no difference in exercise performance having consumed the ketone ester or control drink.
Conclusion: Athletes compensated for the greater acid load caused by ketone ester ingestion by elevating minute ventilation and earlier hyperventilation during incremental exercise.
Purpose
Ingestion of exogenous ketones alters the metabolic response to exercise and may improve exercise performance, but has not been explored in variable intensity team sport activity, or for effects on cognitive function.
Methods
On two occasions in a double-blind, randomised crossover design, eleven male team sport athletes performed the Loughborough Intermittent Shuttle Test (Part A, 5x15 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−1 of a ketone ester supplement (KE). Heart rate (HR), rating of perceived exertion (RPE), and 15 m sprint times were recorded throughout, and serial venous blood samples were assayed for plasma glucose, lactate and β-hydroxybutyrate (βHB).
Results
KE resulted in plasma βHB concentrations of ~1.5 to 2.6 mM during exercise (P < 0.001). Plasma glucose and lactate concentrations were lower during KE compared to PLA (moderate-to-large effect sizes). HR, 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 (95% CI); 268, (199, 336) sec] and KE (229, (178, 280) sec]. Incorrect responses in a multi-tasking test increased from pre- to post-exercise in PLA [1.8 (−0.6, 4.1)] but not KE [0.0 (−1.8, 1.8)] (P = 0.017; d = 0.70).
Conclusion
Compared to carbohydrate alone, co-ingestion of a ketone ester 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.
The purpose of this study was to evaluate whether NaHCO3, administered via a 9-h stacked loading protocol (i.e. repeated supplementation with small doses in order to obtain a gradual increase in blood [HCO3-]), has an ergogenic effect on repeated
all-out exercise. Twelve physically active males were randomly assigned to receive either NaHCO3 (BIC) or placebo (PL) in a double-blind cross-over design. NaHCO3 supplementation was divided in three identical 3-h cycles: a 6.3 g bolus at the start, followed by 2.1 g doses at + 1-h and + 2-h, yielding a total NaHCO3 intake of 0.4 g·kg−1 BM over 9-h. At the end of each cycle, participants performed 2-min all-out cycling. Capillary blood samples were analyzed for [HCO3-], pH and [La-]. Pre-exercise blood [HCO3-] in PL decreased from 25.6 ± 0.2 mmol·L-1 in bout 1 to 23.6 ± 0.2 mmol·L−1 in bout 4, while increasing from 25.5 ± 0.2 to 31.2 ± 0.4 mmol·L−1 in BIC (P < 0.05). Concomitantly, pre- exercise pH values gradually decreased in PL (from 7.41 ± 0.00 to 7.39 ± 0.01) and increased in BIC (from 7.41 ± 0.01 to 7.47 ± 0.01; P < 0.05). Mean power output of the four bouts was higher in BIC (428 ± 20 W) than in PL (420 ± 20 W; P < 0.05). The ergogenic effect on repeated all-out exercise occurred in the absence of gastrointestinal distress.
Exogenous ketone drinks may improve athletic performance and recovery, but information on their gastrointestinal tolerability is limited. Studies to date have used a simplistic reporting methodology that inadequately represents symptom type, frequency, and severity. Herein, gastrointestinal symptoms were recorded during three studies of exogenous ketone monoester (KME) and salt (KS) drinks. Study 1 compared low- and high-dose KME and KS drinks consumed at rest. Study 2 compared KME with isocaloric carbohydrate (CHO) consumed at rest either when fasted or after a standard meal. Study 3 compared KME+CHO with isocaloric CHO consumed before and during 3.25 hr of bicycle exercise. Participants reported symptom type and rated severity between 0 and 8 using a Likert scale at regular intervals. The number of visits with no symptoms reported after ketone drinks was n = 32/60 in Study 1, n = 9/32 in Study 2, and n = 20/42 in Study 3. Following KME and KS drinks, symptoms were acute but mild and were fully resolved by the end of the study. High-dose KS drinks caused greater total-visit symptom load than low-dose KS drinks (13.8 ± 4.3 vs. 2.0 ± 1.0; p < .05) and significantly greater time-point symptom load than KME drinks 1–2 hr postdrink. At rest, KME drinks caused greater total-visit symptom load than CHO drinks (5.0 ± 1.6 vs. 0.6 ± 0.4; p < .05). However, during exercise, there was no significant difference in total-visit symptom load between KME+CHO (4.2 ± 1.0) and CHO (7.2 ± 1.9) drinks. In summary, exogenous ketone drinks cause mild gastrointestinal symptoms that depend on time, the type and amount of compound consumed, and exercise.
This study investigated the effect of the racemic β-hydroxybutyrate (βHB) precursor, R,S-1,3-butanediol (BD), on time-trial (TT) performance and tolerability. A repeated-measures, randomized, crossover study was conducted in nine trained male cyclists (age, 26.7 ± 5.2 years; body mass, 69.6 ± 8.4 kg; height, 1.82 ± 0.09 m; body mass index, 21.2 ± 1.5 kg/m2; VO2peak,63.9 ± 2.5 ml·kg-1·min-1; Wmax, 389.3 ± 50.4 W). Participants ingested 0.35 g/kg of BD or placebo 30 min before and 60 min during 85 min of steady-state exercise, which preceded a ∼25- to 35-min TT (i.e., 7 kJ/kg). The ingestion of BD increased blood D-βHB concentration throughout exercise (0.44-0.79 mmol/L) compared with placebo (0.11-0.16 mmol/L; all p < .001), which peaked 1 hr following the TT (1.38 ± 0.35 vs. 0.34 ± 0.24 mmol/L; p < .001). Serum glucose and blood lactate concentrations were not different between trials (all p > .05). BD ingestion increased oxygen consumption and carbon dioxide production after 20 min of steady-state exercise (p = .002 and p = .032, respectively); however, no further effects on cardiorespiratory parameters were observed. Within the BD trial, moderate to severe gastrointestinal symptoms were reported in five participants, and low levels of dizziness, nausea, and euphoria were reported in two participants. However, this had no effect on TT duration (placebo, 28.5 ± 3.6 min; BD, 28.7 ± 3.2 min; p = .62) and average power output (placebo, 290.1 ± 53.7 W; BD, 286.4 ± 45.9 W; p = .50). These results suggest that BD has no benefit for endurance performance.
Objectives
Ingested ketogenic agents offer the potential to enhance endurance performance via the provision of an alternative exogenous, metabolically efficient, glycogen-sparing fuel (i.e. ketone bodies). This study aimed to assess the impact of combined carbohydrate and 1,3-butanediol (CHO-BD) supplementation on endurance performance, blood beta-hydroxybutyrate (βHB) concentration and glycolytic activity, in comparison to carbohydrate supplementation alone (CHO).
Design
Eleven male runners (age 38 ± 12 years, mass 67.3 ± 6.5 kg, height 174.5 ± 5.0 cm, V˙O2peak 64.2 ± 5.0 ml⋅kg⁻¹⋅min⁻¹) performed two experimental trials in a randomised crossover design.
Methods
Each trial consisted of 60 min of submaximal running, followed by a 5 km running time-trial (TT), and was performed following the ingestion of an energy matched ∼650 ml drink (CHO-BD or CHO).
Results
There was no difference in TT completion time between the trials (CHO: 1265 ± 93, CHO-BD: 1261 ± 96 s; p = 0.723). However, blood βHB concentration in the CHO-BD trial was at least double that of the CHO trial at all time points following supplementation (p < 0.05). While blood lactate concentration was lower in the CHO-BD versus CHO trial after 30 min submaximal exercise (CHO-BD: 1.46 ± 0.67 mmol⋅L⁻¹, CHO: 1.77 ± 0.46 mmol⋅L⁻¹, p = 0.040), it was similar at other time points. Blood glucose concentrations were higher post-TT in the CHO-BD trial (CHO-BD: 5.83 ± 1.02 mmol⋅L⁻¹, CHO: 5.26 ± 0.95 mmol⋅L⁻¹, p = 0.015).
Conclusions
An energy matched CHO-BD supplementation drink raised βHB concentration and acutely lowered blood lactate concentration, without enhancing 5 km TT running performance.