Ruud Van Thienen

[beta]-alanine improves sprint performance in endurance cycling.

PURPOSE Recent research has shown that chronic dietary beta-alanine (betaALA) supplementation increases muscle carnosine content, which is associated with better performance in short (1-2 min) maximal exercise. Success in endurance competitions often depends on a final sprint. However, whether betaALA can be ergogenic in sprint performance at the end of an endurance competition is at present unknown. Therefore, we investigated the effect of 8-wk betaALA administration in moderately to well-trained cyclists on sprint performance at the end of a simulated endurance cycling race. METHODS A double-blind study was performed, which consisted of two experimental test sessions interspersed by an 8-wk betaALA (2-4 g.d; n = 9) or matched placebo (PL; n = 8) supplementation period. In the pretesting and the posttesting, subjects performed a 10-min time trial and a 30-s isokinetic sprint (100 rpm) after a 110-min simulated cycling race. Capillary blood samples were collected for determination of blood lactate concentration and pH. RESULTS Mean power output during the time trial was approximately 300 W and was similar between PL and betaALA during either the pretesting or the posttesting. However, compared with PL, during the final sprint after the time trial, betaALA on average increased peak power output by 11.4% (95% confidence interval = +7.8 to +14.9%, P = 0.0001), whereas mean power output increased by 5.0% (95% confidence interval = +2.0 to +8.1%, P = 0.005). Blood lactate and pH values were similar between groups at any time. CONCLUSION Oral betaALA supplementation can significantly enhance sprint performance at the end of an exhaustive endurance exercise bout.

Dietary nitrate improves muscle but not cerebral oxygenation status during exercise in hypoxia

Exercise tolerance is impaired in hypoxia, and it has recently been shown that dietary nitrate supplementation can reduce the oxygen (O(2)) cost of muscle contractions. Therefore, we investigated the effect of dietary nitrate supplementation on arterial, muscle, and cerebral oxygenation status, symptoms of acute mountain sickness (AMS), and exercise tolerance at simulated 5,000 m altitude. Fifteen young, healthy volunteers participated in three experimental sessions according to a crossover study design. From 6 days prior to each session, subjects received either beetroot (BR) juice delivering 0.07 mmol nitrate/kg body wt/day or a control drink (CON). One session was in normoxia with CON (NOR(CON)); the two other sessions were in hypoxia (11% O(2)), with either CON (HYP(CON)) or BR (HYP(BR)). Subjects first cycled for 20 min at 45% of peak O(2) consumption (VO(2)peak; EX(45%)) and thereafter, performed a maximal incremental exercise test (EX(max)). Whole-body VO(2), arterial O(2) saturation (%SpO(2)) via pulsoximetry, and tissue oxygenation index of both muscle (TOI(M)) and cerebral (TOI(C)) tissue by near-infrared spectroscopy were measured. Hypoxia per se substantially reduced VO(2)peak, %SpO(2), TOI(M), and TOI(C) (NOR(CON) vs. HYP(CON), P < 0.05). Compared with HYP(CON), VO(2) at rest and during EX(45%) was lower in HYP(BR) (P < 0.05), whereas %SpO(2) was higher (P < 0.05). TOI(M) was ~4-5% higher in HYP(BR) than in HYP(CON) both at rest and during EX(45%) and EX(max) (P < 0.05). TOI(C) as well as the incidence of AMS symptoms were similar between HYP(CON) and HYP(BR) at any time. Hypoxia reduced time to exhaustion in EX(max) by 36% (P < 0.05), but this ergolytic effect was partly negated by BR (+5%, P < 0.05). Short-term dietary nitrate supplementation improves arterial and muscle oxygenation status but not cerebral oxygenation status during exercise in severe hypoxia. This is associated with improved exercise tolerance against the background of a similar incidence of AMS.

Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation

In humans, nutrient deprivation and extreme endurance exercise both activate autophagy. We hypothesized that cumulating fasting and cycling exercise would potentiate activation of autophagy in skeletal muscle. Well‐trained athletes were divided into control (n = 8), low‐intensity (LI, n = 8), and high‐intensity (HI, n = 7) exercise groups and submitted to fed and fasting sessions. Muscle biopsy samples were obtained from the vastus lateralis before, at the end, and 1 h after a 2 h LI or HI bout of exercise. Phosphorylation of ULK1Ser317 was higher after exercise (P< 0.001). In both the fed and the fasted states, LC3bII protein level and LC3bII/I were decreased after LI and HI (P < 0.05), while p62/ SQSTM1 was decreased only 1 h after HI (P < 0.05), indicating an increased autophagic flux after HI. The autophagic transcriptional program was also activated, as evidenced by the increased level of LC3b, p62/ SQSTM1, GabarapL1, and Cathepsin L mRNAs observed after HI but not after LI. The increased autophagic flux after HI exercise could be due to increased AMP‐activated protein kinase α (AMPKα) activity, as both AMPKαThr72 and ACCSer79 had a higher phosphorylation state after HI (P < 0.001). In summary, the most effective strategy to activate autophagy in human skeletal muscle seems to rely on exercise intensity more than diet.— Schwalm, C., Jamart, C., Benoit, N., Naslain, D., Prémont, C., Prévet, J., Van Thienen, R., Deldicque, L., Francaux, M. Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation. FASEB J. 29, 3515‐3526 (2015). www.fasebj.org

Effect of acute environmental hypoxia on protein metabolism in human skeletal muscle

Hypoxia‐induced muscle wasting has been observed in several environmental and pathological conditions. However, the molecular mechanisms behind this loss of muscle mass are far from being completely elucidated, certainly in vivo. When studying the regulation of muscle mass by environmental hypoxia, many confounding factors have to be taken into account, such as decreased protein ingestion, sleep deprivation or reduced physical activity, which make difficult to know whether hypoxia per se causes a reduction in muscle mass.

Biochemical artifacts in experiments involving repeated biopsies in the same muscle

Needle biopsies are being extensively used in clinical trials addressing muscular adaptation to exercise and diet. Still, the potential artifacts due to biopsy sampling are often overlooked. Healthy volunteers (n = 9) underwent two biopsies through a single skin incision in a pretest. Two days later (posttest) another biopsy was taken 3 cm proximally and 3 cm distally to the pretest incision. Muscle oxygenation status (tissue oxygenation index [TOI]) was measured by near‐infrared spectroscopy. Biopsy samples were analyzed for 40 key markers (mRNA and protein contents) of myocellular O2 sensing, inflammation, cell proliferation, mitochondrial biogenesis, protein synthesis and breakdown, oxidative stress, and energy metabolism. In the pretest, all measurements were identical between proximal and distal biopsies. However, compared with the pretest, TOI in the posttest was reduced in the proximal (−10%, P < 0.05), but not in the distal area. Conversely, most inflammatory markers were upregulated at the distal (100–500%, P < 0.05), but not at the proximal site. Overall, 29 of the 40 markers measured, equally distributed over all pathways studied, were either up‐ or downregulated by 50–500% (P < 0.05). In addition, 19 markers yielded conflicting results between the proximal and distal measurements (P < 0.05). This study clearly documents that prior muscle biopsies can cause major disturbances in myocellular signaling pathways in needle biopsies specimens sampled 48 h later. In addition, different biopsy sites within identical experimental conditions yielded conflicting results.

Effects of high altitude and cold air exposure on airway inflammation in patients with asthma

Aims Eighteen patients with asthma were evaluated during preparation to climb to extreme altitude in order to study the effects of low fractional inspired oxygen (FiO2), prolonged exposure to cold air and high altitude on lung function, asthma control and airway inflammation. Methods Spirometry and airway inflammation (fractional exhaled nitric oxide (FeNO) and induced sputum) were studied under different test conditions: hypoxic (FiO2=11%) exercise test, 24-hour cold exposure (−5°C) and before, during and after an expedition that involved climbing the Aconcagua mountain (6965 m). Results Forced expiratory volume in 1 s (FEV1) and FeNO values were slightly lower (p<0.04) after 1 h of normobaric hypoxia. FEV1 decreased (p=0.009) after 24-hour cold exposure, accompanied by increased sputum neutrophilia (p<0.01). During the expedition FEV1 and forced vital capacity decreased (maximum FEV1 decrease of 12.3% at 4300 m) and asthma symptoms slightly increased. After the expedition the Asthma Control Test score and prebronchodilator FEV1 were reduced (p<0.02), sputum neutrophil count was increased (p=0.04) and sputum myeloperoxidase levels, sputum interleukin 17 mRNA, serum and sputum vascular endothelial growth factor A levels were significantly higher compared with baseline. Patients with asthma with the lowest oxygen saturation during the hypoxic exercise test were more prone to develop acute mountain sickness. Conclusions Exposure to environmental conditions at high altitude (hypoxia, exercise, cold) was associated with a moderate loss of asthma control, increased airway obstruction and neutrophilic airway inflammation. The cold temperature is probably the most important contributing factor as 24-hour cold exposure by itself induced similar effects.

No effect of dietary nitrate supplementation on endurance training in hypoxia

We investigated whether dietary nitrate (NO3−) supplementation enhances the effect of training in hypoxia on endurance performance at sea level. Twenty‐two healthy male volunteers performed high‐intensity endurance training on a cycle ergometer (6 weeks, 5×30 min/week at 4–6 mmol/L blood lactate) in normobaric hypoxia (12.5% FiO2), while ingesting either beetroot juice [0.07 mmol NO3−/kg body weight (bw)/day; BR, n = 11] or a control drink (CON, n = 11). During the pretest and the posttest, the subjects performed a 30‐min simulated time trial (TT) and an incremental VO2max test. Furthermore, a biopsy was taken from m. vastus lateralis before and after the TT. Power output during the training sessions in both groups increased by ∼6% from week 1 to week 6 (P < 0.05). Compared with the pretest, VO2max in the posttest was increased (P < 0.05) in CON (5%) and BR (9%). Power output corresponding with the 4 mmol/L blood lactate threshold, as well as mean power output during TT increased by ∼16% in both groups (P < 0.05). Muscle phospho‐AMP‐activated protein kinase, hypoxia inducible factor‐1α mRNA content, and glycogen breakdown during the TT were similar between the groups in both the pretest and the posttest. In conclusion, low‐dose dietary NO3− supplementation does not enhance the effects of intermittent hypoxic training on endurance exercise performance at sea level.

Nitrate intake promotes shift in muscle fiber type composition during sprint interval training in hypoxia

Purpose: We investigated the effect of sprint interval training (SIT) in normoxia, vs. SIT in hypoxia alone or in conjunction with oral nitrate intake, on buffering capacity of homogenized muscle (βhm) and fiber type distribution, as well as on sprint and endurance performance. Methods: Twenty-seven moderately-trained participants were allocated to one of three experimental groups: SIT in normoxia (20.9% FiO2) + placebo (N), SIT in hypoxia (15% FiO2) + placebo (H), or SIT in hypoxia + nitrate supplementation (HN). All participated in 5 weeks of SIT on a cycle ergometer (30-s sprints interspersed by 4.5 min recovery-intervals, 3 weekly sessions, 4–6 sprints per session). Nitrate (6.45 mmol NaNO3) or placebo capsules were administered 3 h before each session. Before and after SIT participants performed an incremental VO2max-test, a 30-min simulated cycling time-trial, as well as a 30-s cycling sprint test. Muscle biopsies were taken from m. vastus lateralis. Results: SIT decreased the proportion of type IIx muscle fibers in all groups (P < 0.05). The relative number of type IIa fibers increased (P < 0.05) in HN (P < 0.05 vs. H), but not in the other groups. SIT had no significant effect on βhm. Compared with H, SIT tended to enhance 30-s sprint performance more in HN than in H (P = 0.085). VO2max and 30-min time-trial performance increased in all groups to a similar extent. Conclusion: SIT in hypoxia combined with nitrate supplementation increases the proportion of type IIa fibers in muscle, which may be associated with enhanced performance in short maximal exercise. Compared with normoxic training, hypoxic SIT does not alter βhm or endurance and sprinting exercise performance.

Repeated maximal-intensity hypoxic exercise superimposed to hypoxic residence boosts skeletal muscle transcriptional responses in elite team-sport athletes

To determine whether repeated maximal‐intensity hypoxic exercise induces larger beneficial adaptations on the hypoxia‐inducible factor‐1α pathway and its target genes than similar normoxic exercise, when combined with chronic hypoxic exposure.

Enhanced muscular oxygen extraction in athletes exaggerates hypoxemia during exercise in hypoxia

High rate of muscular oxygen utilization facilitates the development of hypoxemia during exercise at altitude. Because endurance training stimulates oxygen extraction capacity, we investigated whether endurance athletes are at higher risk to developing hypoxemia and thereby acute mountain sickness symptoms during exercise at simulated high altitude. Elite athletes (ATL; n = 8) and fit controls (CON; n = 7) cycled for 20 min at 100 W (EX100W), as well as performed an incremental maximal oxygen consumption test (EXMAX) in normobaric hypoxia (0.107 inspired O2 fraction) or normoxia (0.209 inspired O2 fraction). Cardiorespiratory responses, arterial Po2 (PaO2), and oxygenation status in m. vastus lateralis [tissue oxygenation index (TOIM)] and frontal cortex (TOIC) by near-infrared spectroscopy, were measured. Muscle O2 uptake rate was estimated from change in oxyhemoglobin concentration during a 10-min arterial occlusion in m. gastrocnemius. Maximal oxygen consumption in normoxia was 70 ± 2 ml·min(-1·)kg(-1) in ATL vs. 43 ± 2 ml·min(-1·)kg(-1) in CON, and in hypoxia decreased more in ATL (-41%) than in CON (-25%, P < 0.05). Both in normoxia at PaO2 of ∼95 Torr, and in hypoxia at PaO2 of ∼35 Torr, muscle O2 uptake was twofold higher in ATL than in CON (0.12 vs. 0.06 ml·min(-1)·100 g(-1); P < 0.05). During EX100W in hypoxia, PaO2 dropped to lower (P < 0.05) values in ATL (27.6 ± 0.7 Torr) than in CON (33.5 ± 1.0 Torr). During EXMAX, but not during EX100W, TOIM was ∼15% lower in ATL than in CON (P < 0.05). TOIC was similar between the groups at any time. This study shows that maintenance of high muscular oxygen extraction rate at very low circulating PaO2 stimulates the development of hypoxemia during submaximal exercise in hypoxia in endurance-trained individuals. This effect may predispose to premature development of acute mountain sickness symptoms during exercise at altitude.