Chiel Poffé

Ketone ester (KE) intake attenuates the ventilatory response to O ₂ and CO ₂ after 20 h at 3,375 m, and this most likely results from hyperventilation induced by KE intake, rather than reflecting altered ventilatory reactivity to O ₂ and/or CO ₂ per se. Conversely, despite accentuated acid-base disruptions, ketosis did not affect cerebrovascular parameters.

In hypoxia, endurance performance, sleep, and cognitive function are impaired. Ketone ester (KE) intake can elevate blood, brain, and skeletal muscle oxygenation, making it an interesting strategy to attenuate hypoxia‐induced impairments. Given that acute mountain sickness (AMS) influences these parameters, we evaluated the effects of KE intake in non‐AMS developing individuals. In a larger project, 14 young, healthy, male participants performed a 29‐h protocol at a simulated altitude of 4000–4500 m, involving regular KE or placebo intake. Five participants completed both sessions without developing severe AMS. They completed two maximal incremental cycling tests after 1.5 and 25 h (EX _MAX1 and EX _MAX2 , resp.) and a combined maximal‐submaximal test after 26.5 h (EX _COMBO ), while resting blood, brain, and skeletal muscle oxygenation and cognitive function were regularly (5‐6x) evaluated, and sleep was analyzed. KE did not alter peak power output (PPO) during EX _MAX1 or EX _MAX2 , but increased PPO by 36 W during EX _COMBO . KE increased blood oxygenation before EX _MAX1 , EX _MAX2 , and EX _COMBO and increased muscle oxygenation only before EX _COMBO . Sleep and cognitive function were not affected by KE intake. In a non‐AMS developing subgroup, KE appears effective to attenuate high‐intensity endurance performance decline during subacute hypoxic exposure accompanied by repeated exercise until exhaustion.

Evidence suggests that exogenous ketosis (EK) induced by ketone monoester (KME) supports recovery and attenuates physiological stress during endurance exercise. However, the potential benefits of the ketone precursor R‐1,3‐butanediol (BDO) during real‐world multi‐stage cycling remain unknown. We investigated the effects of post‐exercise BDO supplementation on physiological strain, dietary intake, hydration, cognitive function, sleep, and subjective recovery during the 2025 Absa Cape Epic mountain bike race. In this double‐blind, placebo‐controlled study, 18 trained mountain bikers (10 teams) completed an 8‐day multi‐stage race. Participants received either 87.5 mL ketone IQ (BDO) or a placebo (CON) twice daily (post‐stage and pre‐sleep). Heart rate, energy intake, sleep metrics, cognitive performance, and subjective stress‐recovery were monitored throughout the race. BDO induced mild post‐stage ketosis (∼1.0 mM β ‐hydroxybutyrate) from stage 1 onwards. Across the race, both groups demonstrated lower exercise heart rate, increased resting heart rate, increased energy and carbohydrate intake, and slower reaction time by stage 6, indicating accumulating physiological strain. BDO did not alter any of these effects compared with placebo. These findings suggest that the modest ketosis achieved with BDO was not effective under real‐world racing conditions, highlighting the importance of formulation‐specific and ecologically valid evaluations of exogenous ketosis strategies in future studies.

Purpose: Intermittent exogenous ketosis via ketone monoester (KE) ingestion has been shown to enhance physiological responses and reduce acute mountain sickness (AMS) symptoms during acute normobaric hypoxia. Its effects during early acclimatization to terrestrial high-altitude, however, remain unclear. Methods: Thirty-four participants were randomised to an intermittent exogenous ketosis (IEK, n =17) or placebo (PLA, n =17) group and underwent a near sea level trial (295 m) without supplementation, followed by a four-day sojourn at 3375 m during which they received regular KE (IEK) or placebo (PLA) supplements. AMS symptoms, hematological markers, and resting ventilatory, cardiovascular, and cerebral tissue oxygenation responses were assessed each day upon waking, at midday, and before sleep throughout the exposure. Results: KE consistently elevated circulating β-hydroxybutyrate post-ingestion ( P vs . PLA across the altitude exposure ( P ≥0.822). KE ingestion induced (keto)acidosis, resulting in augmented ventilatory response in IEK ( P ≤0.037), but failed to mitigate hypoxia-induced blood and cerebral deoxygenation relative to PLA ( P ≥0.234). KE ingestion increased daytime cardiac output and lowered morning blood pressure in IEK ( P ≤0.031), while it did not affect autonomic, eryrthropoietic, or redox responses compared to PLA ( P ≥0.099). Conclusion: Although KE alters some physiological responses, it does not seem to importantly modulate AMS incidence and severity during early terrestrial altitude acclimatization.

Regular physical activity improves vascular function and promotes angiogenesis and erythropoiesis, which are further augmented by hypoxia. Early evidence suggests that long‐term exogenous ketosis (EK) can enhance vascular function and angiogenesis. However, the acute responses and underlying mechanisms remain unknown. Moreover, acute and prolonged EK may increase blood erythropoietin (EPO) concentrations in normoxia. Nonetheless, whether this effect is additive to hypoxia is unclear, as an EK‐mediated attenuation of blood deoxygenation may counteract the [EPO] increase. In a randomized, placebo‐controlled, crossover design, 13 male and two female participants completed four experimental sessions. Each included a high‐intensity interval training session, followed by recovery either in normoxia or normobaric hypoxia (3000 m simulated altitude, : 14.5%), supplemented with placebo or the commercial ketone precursor Ketone‐IQ®. Macro‐ and microvascular function were assessed throughout a vascular occlusion protocol, using femoral artery blood flow and muscle oxygenation, respectively, after 2.5 and 5.5 h recovery. Additionally, serum EPO and endothelin‐1 (ET‐1) concentrations, and skeletal muscle expression of pro‐angiogenic and vascular integrity markers were evaluated. In normoxia and hypoxia, EK increased post‐occlusion blood velocity (+15%) and muscle reoxygenation rate (+9%). Furthermore, muscle expression of pro‐angiogenic and vascular integrity markers (including vascular endothelial growth factor, peroxisome proliferator‐activated receptor γ coactivator 1α, and angiopoietin‐1) as well as serum [EPO] (+15%) increased with EK, while serum [ET‐1] was reduced (−13%). EK appears as a promising strategy to enhance vascular function and integrity, angiogenic signalling, and circulating [EPO] in response to exercise and hypoxia, thereby facilitating beneficial adaptive responses. image Key points: Exogenous ketosis (EK) enhances macro‐ and microvascular function during post‐exercise recovery, in both normoxia and hypoxia, likely through reducing serum [ET‐1]. Moreover, EK upregulates markers of exercise‐induced angiogenesis and vascular integrity. Finally, an EK‐related, post‐exercise increase in serum [EPO] is additive to hypoxic exposure alone.

This study demonstrates that intermittent exogenous ketosis does not alter the high-altitude slowing of the primary phase of V̇o ₂ kinetics during the transition to heavy-intensity exercise, nor does it change ventilatory, gas exchange, blood or tissue oxygenation responses, or whole-body efficiency across 3 days at 3,375 m. However, preexercise ketone monoester ingestion increased cardiac output during moderate-intensity exercise on arrival to 3,375 m and after 24 h, but this did not translate to broader physiological benefits.

This study is the first to demonstrate the effects of ketone ester ingestion on hypoxia-induced neural alterations. Moreover, it uniquely combines measurements of cerebral oxygenation, cognitive performance, and electroencephalography (EEG) across low-, high-, and all-out exercise intensities, as well as during rest. Potentially highlighting EEG as a valuable tool for monitoring fatigue and optimizing training strategies.

Post‐exercise ketone supplementation (PEKS) previously improved endurance performance and muscular adaptations during overload training. However, whether and how PEKS improves endurance performance during a periodised endurance training period remains unclear. Twenty‐eight trained males completed 8 weeks of supervised cycling, receiving either 25 g of the ketone monoester ( R )‐hydroxybutyl ( R )‐hydroxybutyrate (KE, n = 14) or isocaloric placebo (CON, n = 14) post‐exercise and before sleep. Outcomes included exercise performance and muscular/cardiac adaptations assessed at baseline (PRE), week 3 (MID) and 7 (POST), and following a taper week (POST _+1week ). The training intervention improved 30 min time trial performance (TT _30min ), absolute and relative , peak power output during the test (PPO ), citrate synthase (CS) activity, and peak cardiac output (all P < 0.05 PRE vs . POST). Notably, TT _30min (CON: 291 ± 27 W vs . KE: 302 ± 28 W, P < 0.001, Hedges’ g = 0.40) was 4% higher in KE compared to CON at POST. Although peak cardiac output was similar, relative increased more in KE (+12%) than CON (+6%, Δ P < 0.001), suggesting enhanced peripheral oxygen utilisation. Accordingly, CS activity was at POST 14% higher in KE (9.37 ± 1.36 mol h ⁻¹ kg protein ⁻¹ ) compared to CON (8.21 ± 0.97 mol h ⁻¹ kg protein ⁻¹ , P = 0.035, Hedges’ g = 0.98) and OXPHOS complex II muscle protein content remained unaltered in CON while increasing by 25% in KE ( P = 0.030 vs . PRE). In conclusion, these findings establish PEKS as a nutritional strategy to enhance endurance performance and mitochondrial adaptations during periodised endurance training. image Key points: Previous research showed that post‐exercise ketone ester (KE) supplementation improves endurance performance and muscle adaptations during 3 weeks of excessive endurance exercise. Whether KE ingestion enhances performance, muscular and cardiac adaptations during a periodised endurance training intervention remained unknown. We demonstrate that KE supplementation post‐exercise and before sleep during an 8 week periodised endurance training period enhances endurance performance and peak oxygen uptake rate in trained male participants. These performance improvements were mediated by muscular adaptations (e.g. increased mitochondrial content), while cardiac adaptations were not affected by KE. Our findings show that KE enhances endurance performance primarily by muscular adaptations, indicating that post‐exercise KE supplementation is effective to amplify endurance exercise training adaptations.