Exogenous ketosis increases blood and muscle oxygenation but not performance during exercise in hypoxia

Author(s):  
Chiel Poffe ◽  
Ruben Robberechts ◽  
Tim Podlogar ◽  
Martijn Kusters ◽  
Tadej Debevec ◽  
...  

Available evidence indicates that elevated blood ketones are associated with improved hypoxic tolerance in rodents. From this perspective, we hypothesized that exogenous ketosis by oral intake of the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) may induce beneficial physiological effects during prolonged exercise in acute hypoxia. As we recently demonstrated KE to deplete blood bicarbonate, which per se may alter the physiological response to hypoxia, we evaluated the effect of KE both in the presence and absence of bicarbonate intake (BIC). Fourteen highly trained male cyclists performed a simulated cycling race (RACE) consisting of 3h intermittent cycling (IMT180') followed by a 15-min time-trial (TT15') and an all-out sprint at 175% of lactate threshold (SPRINT). During RACE, fraction of inspired oxygen (FiO2) was gradually decreased from 18.6 to 14.5%. Before and during RACE, participants received either i) 75g ketone ester (KE), ii) 300 mg/kg body mass bicarbonate (BIC), iii) KE+BIC or iv) a control drink in addition to 60g carbohydrates per h in a randomized, crossover design. KE counteracted the hypoxia-induced drop in blood (SpO2) and muscle oxygenation by ~3%. In contrast, BIC decreased SpO2 by ~2% without impacting muscle oxygenation. Performance during TT15' and SPRINT were similar between all conditions. In conclusion, KE slightly elevated the degree of blood and muscle oxygenation during prolonged exercise in moderate hypoxia without impacting exercise performance. Our data warrant to further investigate the potential of exogenous ketosis to improve muscular and cerebral oxygenation status, and exercise tolerance in extreme hypoxia.

2007 ◽  
Vol 103 (1) ◽  
pp. 177-183 ◽  
Author(s):  
Andrew W. Subudhi ◽  
Andrew C. Dimmen ◽  
Robert C. Roach

To determine if fatigue at maximal aerobic power output was associated with a critical decrease in cerebral oxygenation, 13 male cyclists performed incremental maximal exercise tests (25 W/min ramp) under normoxic (Norm: 21% FiO2) and acute hypoxic (Hypox: 12% FiO2) conditions. Near-infrared spectroscopy (NIRS) was used to monitor concentration (μM) changes of oxy- and deoxyhemoglobin (Δ[O2Hb], Δ[HHb]) in the left vastus lateralis muscle and frontal cerebral cortex. Changes in total Hb were calculated (Δ[THb] = Δ[O2Hb] + Δ[HHb]) and used as an index of change in regional blood volume. Repeated-measures ANOVA were performed across treatments and work rates (α = 0.05). During Norm, cerebral oxygenation rose between 25 and 75% peak power output {Powerpeak; increased (inc) Δ[O2Hb], inc. Δ[HHb], inc. Δ[THb]}, but fell from 75 to 100% Powerpeak {decreased (dec) Δ[O2Hb], inc. Δ[HHb], no change Δ[THb]}. In contrast, during Hypox, cerebral oxygenation dropped progressively across all work rates (dec. Δ[O2Hb], inc. Δ[HHb]), whereas Δ[THb] again rose up to 75% Powerpeak and remained constant thereafter. Changes in cerebral oxygenation during Hypox were larger than Norm. In muscle, oxygenation decreased progressively throughout exercise in both Norm and Hypox (dec. Δ[O2Hb], inc. Δ [HHb], inc. Δ[THb]), although Δ[O2Hb] was unchanged between 75 and 100% Powerpeak. Changes in muscle oxygenation were also greater in Hypox compared with Norm. On the basis of these findings, it is unlikely that changes in cerebral oxygenation limit incremental exercise performance in normoxia, yet it is possible that such changes play a more pivotal role in hypoxia.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Georgia G. Tsaousi ◽  
Ioakeim Pezikoglou ◽  
Anastasia Nikopoulou ◽  
Nicolaos G. Foroglou ◽  
Aikaterina Poulopoulou ◽  
...  

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Ruzhou Zhao ◽  
Xingcheng Zhao ◽  
Xiaobo Wang ◽  
Yanqi Liu ◽  
Jie Yang ◽  
...  

AbstractRapid adaptation to a hypoxic environment is an unanswered question that we are committed to exploring. At present, there is no suitable strategy to achieve rapid hypoxic adaptation. Here, we demonstrate that fasting preconditioning for 72 h reduces tissue injuries and maintains cardiac function, consequently significantly improving the survival rates of rats under extreme hypoxia, and this strategy can be used for rapid hypoxic adaptation. Mechanistically, fasting reduces blood glucose and further suppresses tissue mTOR activity. On the one hand, fasting-induced mTOR inhibition reduces unnecessary ATP consumption and increases ATP reserves under acute hypoxia as a result of decreased protein synthesis and lipogenesis; on the other hand, fasting-induced mTOR inhibition improves mitochondrial oxygen utilization efficiency to ensure ATP production under acute hypoxia, which is due to the significant decrease in ROS generation induced by enhanced mitophagy. Our findings highlight the important role of mTOR in acute hypoxic adaptation, and targeted regulation of mTOR could be a new strategy to improve acute hypoxic tolerance in the body.


1977 ◽  
Vol 43 (2) ◽  
pp. 258-261 ◽  
Author(s):  
F. Pirnay ◽  
M. Lacroix ◽  
F. Mosora ◽  
A. Luyckx ◽  
P. Lefebvre

By use of naturally enriched [13C]glucose as metabolic tracer, the utilization of exogenous glucose ingested during muscular exercise was investigated. Four subjects walked on an uphill treadmill for 2 h, and three other for 4 h. The energy expenditure, close to 50% of the individual maximum Vo2,, varied from 1.9 to 2.1 liters of O2/min, while the heart rate ranged between 142 and 165 beats/mm. The subjects who were on a mixed diet and had fasted overnight, were given 100 g of naturally labeled [13C]glucose. Following this intake? the expired CO2 became rapidly enriched in carbon-13. The increase was observed as early as 15 min after the oral intake, and reached a maximum within 1–2 h, when utilization of exogenous glucose varied between 500 and 650 mg/min, representing as much as 55% of the carbohydrate metabolism and 24% of the total energy expenditure. glucose metabolism; man; mass spectrometry; stable isotopes


2007 ◽  
Vol 102 (1) ◽  
pp. 286-293 ◽  
Author(s):  
Charles F. Zwemer ◽  
Michael Y. Song ◽  
Katari A. Carello ◽  
Louis G. D'Alecy

Some mammals respond to hypoxia by lowering metabolic demand for oxygen and others by maximizing efficiency of oxygen usage: the former strategy is generally held to be the more effective. We describe within the same species one outbred strain (CD-1) that lowers demand and another inbred strain (C57BL/6J) that maximizes oxygen efficiency to markedly extend hypoxic tolerance. Unanesthetized adult male mice ( Mus musculus, CD-1 and C57BL/6J) between 20 and 35 g were used. Sham-conditioned (SC) C57BL/6J mice survived severe hypoxia (4.5% O2, balance N2) roughly twice as long as SC CD-1 mice (median 211 and 93.5 s, respectively; P < 0.0001). Following acute hypoxic conditioning (HC), C57BL/6J mice survived subsequent hypoxia 10 times longer than HC CD-1 mice (median 2,198 and 238 s respectively; P < 0.0001). Therefore, C57BL/6J mice are both naturally more tolerant to hypoxia and show a greater increase in hypoxic tolerance in response to hypoxic conditioning. Indirect calorimetry indicates that CD-1 mice lower mass-specific oxygen consumption (V̇′o2 in ml O2·kg−1·min−1) and carbon dioxide production (V̇′co2 in ml CO2·kg−1·min−1) in response to HC ( P = 0.002 and P < 0.0001, respectively), but C57BL/6J mice maintain V̇′o2 and V̇′co2 after HC. Respiratory exchange ratio and fluorometric assay of plasma ketones suggest that C57BL/6J mice rapidly switch to ketone metabolism, a more efficient substrate, while CD-1 mice reduce overall metabolic activity. We conclude that under severe hypoxia in mice, switching fuel, possibly to ketones, while maintaining V̇′o2, may confer a greater survival advantage than simply lowering demand.


1992 ◽  
Vol 73 (6) ◽  
pp. 2701-2708 ◽  
Author(s):  
H. J. Green ◽  
J. R. Sutton ◽  
E. E. Wolfel ◽  
J. T. Reeves ◽  
G. E. Butterfield ◽  
...  

To determine whether the working muscle is able to sustain ATP homeostasis during a hypoxic insult and the mechanisms associated with energy metabolic adaptations during the acclimatization process, seven male subjects [23 +/- 2 (SE) yr, 72.2 +/- 1.6 kg] were given a prolonged exercise challenge (45 min) at sea level (SL), within 4 h after ascent to an altitude of 4,300 m (acute hypoxia, AH), and after 3 wk of sustained residence at 4,300 m (chronic hypoxia, CH). The prolonged cycle test conducted at the same absolute intensity and representing 51 +/- 1% of SL maximal aerobic power (VO2 max) and between 64 +/- 2 (AH) and 66 +/- 1% (CH) at altitude was performed without a reduction in ATP concentration in the working vastus lateralis regardless of condition. Compared with rest, exercise performed during AH resulted in a greater increase (P < 0.05) in muscle lactate concentration (5.11 +/- 0.68 to 22.3 +/- 6.1 mmol/kg dry wt) than exercise performed either at SL (5.88 +/- 0.85 to 11.5 +/- 3.1) or CH (5.99 +/- 0.88 to 12.4 +/- 2.1). These differences in lactate concentration have been shown to reflect differences in arterial lactate concentration and glycolysis (Brooks et al. J. Appl. Physiol. 71: 333–341, 1991). The reduction in glycolysis at least between AH and CH appears to be accompanied by a tighter metabolic control. During CH, free ADP was lower and the ATP-to-free ADP ratio was increased (P < 0.05) compared with AH.(ABSTRACT TRUNCATED AT 250 WORDS)


2015 ◽  
Author(s):  
Ben J Lee ◽  
Charles D Thake

Background. The purpose of this study was to assess the reproducibility of cardiorespiratory and cellular (monocyte heat shock protein 70; mHSP70) responses to a fixed load hypoxic stress test (HST) and the reliability of a pre-loaded 16.1km cycling time trial (pTT) conducted under both normoxic and hypoxic conditions. Methods. Eighteen participants (age, 22 ± 4 years; height, 1.77 ± 0.04 meters; body mass, 76.8 kg; estimated body fat and VO2peak = 3.50 ± 0.60 L.min-1) were divided into three groups. Reliability of responses (HR, SPO2, VO2, VCO2, VE and RER) to the HST (FIO2 0.14; 15 minutes rest, 60 minutes cycling at 50% normoxic VO2peak) was assessed across 3 repeat trials (HST 1, 2 and 3, n = 6); mHSP70 was measured via flow cytometry before and after each HST (n = 5); resting HSP was also quantified on 4 separate occasions (n=5). Reliability of the pTT (15 min rest, 40 minutes cycling at 50% normoxic VO2peak) was assessed across 3 repeat normoxic (N; FIO2 ≈ 0.21; n=6) and 3 repeat hypoxic (FIO2 ≈ 0.14; n = 6) trials. All exercise trials were undertaken at the same time of day, following exercise and dietary controls, 7 days apart. Results. Intra-class correlation coefficients (ICC’s) for mean and peak HR, SpO2, VE , VO2 , VCO2 and BLa within each trial were improved from HST1 to HST2 (mean data: 0.99, 0.95, 0.75, 0.62, 0.70, 0.90; peak data: 0.98, 0.96, 0.64, 0.69, 0.74, 0.75) to HST2 and HST3 (ICC = 0.99, 0.97, 0.82, 0.85, 0.87 and 0.96 respectively). mHSP70 was a reproducible at rest without (ICC > 0.95) and with HSTs conducted in the previous 7 days (ICC > 0.95), with no difference in pre to post increases in mHSP70 observed between tests. The reliability for time to pTT completion was improved following one trial, and the CV (test 2 vs. 3) was similar under normoxic (CV = 0.62) and hypoxic conditions (CV = 0.63). Conclusion. Cardiorespiratory and cellular responses to the HST were reproducible and the pTT performance time reliable in both N and H. Since the reproducibility of the measurements in HST trials and reliability of pTT improved between the second and third trials one familiarization visit is recommended prior to employing these protocols in future studies.


2001 ◽  
Vol 33 (5) ◽  
pp. S263
Author(s):  
T Mimura ◽  
S Tanaka ◽  
K Ishihara ◽  
T Wadazumi ◽  
T Miyamoto ◽  
...  

2009 ◽  
Vol 19 (3) ◽  
pp. 275-284 ◽  
Author(s):  
Carl J. Hulston ◽  
Asker E. Jeukendrup

The purpose of this study was to investigate the possibility of a placebo effect from carbohydrate (CHO) intake during prolonged exercise. Ten endurance-trained male cyclists performed 3 experimental trials consisting of 120 min of steady-state cycling at 61% VO2max followed by a time trial (TT) lasting approximately 60 min. During exercise participants ingested either plain water (WAT), artificially colored and flavored water (PLA), or a 6% carbohydrate-electrolyte solution (CES). PLA and CES were produced with identical color and taste. To investigate the possibility of a placebo effect from CHO intake, participants were told that both flavored solutions contained CHO and that the purpose of the study was to compare CHO drinks with water. Mean power output during TT was 218 ± 22 W in WAT, 219 ± 17 W in PLA, and 242 ± 27 W in CES. Performance times were 66.35 ± 6.15, 65.94 ± 5.56, and 59.69 ± 2.87 min for WAT, PLA, and CES, respectively. Therefore, CES ingestion enhanced TT performance by 11.3% compared with WAT (p < .05) and 10.6% compared with PLA (p < .05), with no difference between PLA and WAT. In conclusion, during a prolonged test of cycling performance, in which participants were not fully informed of the test conditions, there was no placebo effect when participants believed they had ingested CHO. In contrast, the real effect of CHO intake was a 10.6% improvement in TT cycling performance.


2015 ◽  
Vol 118 (2) ◽  
pp. 156-162 ◽  
Author(s):  
J. Santos-Concejero ◽  
F. Billaut ◽  
L. Grobler ◽  
J. Oliván ◽  
T. D. Noakes ◽  
...  

The purpose of this study was to analyze the cerebral oxygenation response to maximal self-paced and incremental exercise in elite Kenyan runners from the Kalenjin tribe. On two separate occasions, 15 elite Kenyan distance runners completed a 5-km time trial (TT) and a peak treadmill speed test (PTS). Changes in cerebral oxygenation were monitored via near-infrared spectroscopy through concentration changes in oxy- and deoxyhemoglobin (Δ[O2Hb] and Δ[HHb]), tissue oxygenation index (TOI), and total hemoglobin index (nTHI). During the 5-km TT (15.2 ± 0.2 min), cerebral oxygenation increased over the first half (increased Δ[O2Hb] and Δ[HHb]) and, thereafter, Δ[O2Hb] remained constant (effect size, ES = 0.33, small effect), whereas Δ[HHb] increased until the end of the trial ( P < 0.05, ES = 3.13, large effect). In contrast, during the PTS, from the speed corresponding to the second ventilatory threshold, Δ[O2Hb] decreased ( P < 0.05, ES = 1.51, large effect), whereas Δ[HHb] continued to increase progressively until exhaustion ( P < 0.05, ES = 1.22, large effect). Last, the TOI was higher during the PTS than during the 5-km TT ( P < 0.001, ES = 3.08; very large effect), whereas nTHI values were lower ( P < 0.001, ES = 2.36, large effect). This study shows that Kenyan runners from the Kalenjin tribe are able to maintain their cerebral oxygenation within a stable range during a self-paced maximal 5-km time trial, but not during an incremental maximal test. This may contribute to their long-distance running success.


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