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Marching to the Beet: The effect of dietary nitrate supplementation on high altitude exercise performance and adaptation during a military trekking expedition.
Marshall, AR, Rimmer, JE, Shah, N, Bye, K, Kipps, C, Woods, DR, O'Hara, J, Boos, CJ, Barlow, M
Nitric oxide : biology and chemistry. 2021;:70-77
Abstract
PURPOSE The aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia). METHODS This was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28 ± 12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70 ml dose per day of either BRJ (~12.5 mmol nitrate per day; n = 11) or non-nitrate calorie matched control (n = 11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800 m) reached on day 17 of the expedition. Data were collected at baseline (44 m altitude), at 2350 m (day 9), 3400 m (day 12) and 4800 m (day 17). RESULTS BRJ enhanced the salivary levels of nitrite (p = 0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=<0.001). Harvard Step Test fitness scores significantly declined at 4800 m in the control group (p = 0.003) compared with baseline. In contrast, there was no decline in fitness scores at 4800 m compared with baseline (p = 0.26) in the BRJ group. Heart rate recovery speed following exercise at 4800 m was significantly prolonged in the control group (p=<0.01) but was unchanged in the BRJ group (p = 0.61). BRJ did not affect the burden of HA illness (p = 1.00). CONCLUSIONS BRJ increases salivary nitrite levels and ameliorates the decline in fitness at altitude but does not affect the occurrence of HA illness.
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Independent and combined impact of hypoxia and acute inorganic nitrate ingestion on thermoregulatory responses to the cold.
Arnold, JT, Bailey, SJ, Hodder, SG, Fujii, N, Lloyd, AB
European journal of applied physiology. 2021;(4):1207-1218
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Abstract
PURPOSE This study assessed the impact of normobaric hypoxia and acute nitrate ingestion on shivering thermogenesis, cutaneous vascular control, and thermometrics in response to cold stress. METHOD Eleven male volunteers underwent passive cooling at 10 °C air temperature across four conditions: (1) normoxia with placebo ingestion, (2) hypoxia (0.130 FiO2) with placebo ingestion, (3) normoxia with 13 mmol nitrate ingestion, and (4) hypoxia with nitrate ingestion. Physiological metrics were assessed as a rate of change over 45 min to determine heat loss, and at the point of shivering onset to determine the thermogenic thermoeffector threshold. RESULT Independently, hypoxia expedited shivering onset time (p = 0.05) due to a faster cooling rate as opposed to a change in central thermoeffector thresholds. Specifically, compared to normoxia, hypoxia increased skin blood flow (p = 0.02), leading to an increased core-cooling rate (p = 0.04) and delta change in rectal temperature (p = 0.03) over 45 min, yet the same rectal temperature at shivering onset (p = 0.9). Independently, nitrate ingestion delayed shivering onset time (p = 0.01), mediated by a change in central thermoeffector thresholds, independent of changes in peripheral heat exchange. Specifically, compared to placebo ingestion, no difference was observed in skin blood flow (p = 0.5), core-cooling rate (p = 0.5), or delta change in rectal temperature (p = 0.7) over 45 min, while nitrate reduced rectal temperature at shivering onset (p = 0.04). No interaction was observed between hypoxia and nitrate ingestion. CONCLUSION These data improve our understanding of how hypoxia and nitric oxide modulate cold thermoregulation.
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Effect of hypoxic exercise on glucose tolerance in healthy and prediabetic adults.
De Groote, E, Britto, FA, Balan, E, Warnier, G, Thissen, JP, Nielens, H, Sylow, L, Deldicque, L
American journal of physiology. Endocrinology and metabolism. 2021;(1):E43-E54
Abstract
This study aimed to investigate the mechanisms known to regulate glucose homeostasis in human skeletal muscle of healthy and prediabetic subjects exercising in normobaric hypoxia. Seventeen healthy (H; 28.8 ± 2.4 yr; maximal oxygen consumption (V̇O2max): 45.1 ± 1.8 mL·kg-1·min-1) and 15 prediabetic (P; 44.6 ± 3.9 yr; V̇O2max: 30.8 ± 2.5 mL·kg-1·min-1) men were randomly assigned to two groups performing an acute exercise bout (heart rate corresponding to 55% V̇O2max) either in normoxic (NE) or in hypoxic (HE; fraction of inspired oxygen [Formula: see text] 14.0%) conditions. An oral glucose tolerance test (OGTT) was performed in a basal state and after an acute exercise bout. Muscle biopsies from m. vastus lateralis were taken before and after exercise. Venous blood samples were taken at regular intervals before, during, and after exercise. The two groups exercising in hypoxia had a larger area under the curve of blood glucose levels during the OGTT after exercise compared with baseline (H: +11%; P: +4%). Compared with pre-exercise, an increase in p-TBC1D1 Ser237 and in p-AMPK Thr172 was observed postexercise in P NE (+95%; +55%, respectively) and H HE (+91%; +43%, respectively). An increase in p-ACC Ser212 was measured after exercise in all groups (H NE: +228%; P NE +252%; H HE +252%; P HE +208%). Our results show that an acute bout of exercise in hypoxia reduces glucose tolerance in healthy and prediabetic subjects. At a molecular level, some adaptations regulating glucose transport in muscle were found in all groups without associations with glucose tolerance after exercise. The results suggest that hypoxia negatively affects glucose tolerance postexercise through unidentified mechanisms.NEW & NOTEWORTHY The molecular mechanisms involved in glucose tolerance after acute exercise in hypoxia have not yet been elucidated in human. Due to the reversible character of their status, prediabetic individuals are of particular interest for preventing the development of type 2 diabetes. The present study is the first to investigate muscle molecular mechanisms during exercise and glucose metabolism after exercise in prediabetic and healthy subjects exercising in normoxia and normobaric hypoxia.
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The effect of β-alanine supplementation on high intensity cycling capacity in normoxia and hypoxia.
Patel, KA, Farias de Oliveira, L, Sale, C, James, RM
Journal of sports sciences. 2021;(11):1295-1301
Abstract
The availability of dietary beta-alanine (BA) is the limiting factor in carnosine synthesis within human muscle due to its low intramuscular concentration and substrate affinity. Carnosine can accept hydrogen ions (H+), making it an important intramuscular buffer against exercise-induced acidosis. Metabolite accumulation rate increases when exercising in hypoxic conditions, thus an increased carnosine concentration could attenuate H+ build-up when exercising in hypoxic conditions. This study examined the effects of BA supplementation on high intensity cycling capacity in normoxia and hypoxia. In a double-blind design, nineteen males were matched into a BA group (n = 10; 6.4 g·d-1) or a placebo group (PLA; n = 9) and supplemented for 28 days, carrying out two pre- and two post-supplementation cycling capacity trials at 110% of powermax, one in normoxia and one in hypoxia (15.5% O2). Hypoxia led to a 9.1% reduction in exercise capacity, but BA supplementation had no significant effect on exercise capacity in normoxia or hypoxia (P > 0.05). Blood lactate accumulation showed a significant trial x time interaction post-supplementation (P = 0.016), although this was not significantly different between groups. BA supplementation did not increase high intensity cycling capacity in normoxia, nor did it improve cycling capacity in hypoxia even though exercise capacity was reduced under hypoxic conditions.
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Blood glucose concentration is unchanged during exposure to acute normobaric hypoxia in healthy humans.
Chan, JS, Chiew, AE, Rimke, AN, Chan, G, Rampuri, ZH, Kozak, MD, Boulé, NG, Steinback, CD, Davenport, MH, Day, TA
Physiological reports. 2021;(15):e14932
Abstract
Normal blood [glucose] regulation is critical to support metabolism, particularly in contexts of metabolic stressors (e.g., exercise, high altitude hypoxia). Data regarding blood [glucose] regulation in hypoxia are inconclusive. We aimed to characterize blood [glucose] over 80 min following glucose ingestion during both normoxia and acute normobaric hypoxia. In a randomized cross-over design, on two separate days, 28 healthy participants (16 females; 21.8 ± 1.6 years; BMI 22.8 ± 2.5 kg/m2 ) were randomly exposed to either NX (room air; fraction of inspired [FI ]O2 ~0.21) or HX (FI O2 ~0.148) in a normobaric hypoxia chamber. Measured FI O2 and peripheral oxygen saturation were both lower at baseline in hypoxia (p < 0.001), which was maintained over 80 min, confirming the hypoxic intervention. Following a 10-min baseline (BL) under both conditions, participants consumed a standardized glucose beverage (75 g, 296 ml) and blood [glucose] and physiological variables were measured at BL intermittently over 80 min. Blood [glucose] was measured from finger capillary samples via glucometer. Initial fasted blood [glucose] was not different between trials (NX:4.8 ± 0.4 vs. HX:4.9 ± 0.4 mmol/L; p = 0.47). Blood [glucose] was sampled every 10 min (absolute, delta, and percent change) following glucose ingestion over 80 min, and was not different between conditions (p > 0.77). In addition, mean, peak, and time-to-peak responses during the 80 min were not different between conditions (p > 0.14). There were also no sex differences in these blood [glucose] responses in hypoxia. We conclude that glucose regulation is unchanged in young, healthy participants with exposure to acute steady-state normobaric hypoxia, likely due to counterbalancing mechanisms underlying blood [glucose] regulation in hypoxia.
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Effects of carbohydrate and glutamine supplementation on cytokine production by monocytes after exercise in hypoxia: A crossover, randomized, double-blind pilot study.
Caris, AV, Tavares-Silva, E, Thomatieli-Santos, RV
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:110592
Abstract
OBJECTIVES The aim of this study was to evaluate the combined effects of carbohydrate (CHO) and glutamine (Gln) supplementation on cytokine production by monocytes after exercise until exhaustion performed in hypoxia. METHODS Fifteen physically active men underwent three exercises until exhaustion with an intensity of 70% maximal oxygen intake at a simulated height of 4500 m under the following supplementation: placebo, CHO (maltodextrin 8%/200 mL for 20 min), and CHO + Gln (Gln 20 g/d for 6 d and maltodextrin 8%/200 mL for 20 min) during exercise and for 2 h of recovery. Analysis of variance for repeated measures followed by the Tukey's post hoc test was realized and P < 0.05 was considered statistically significant. RESULTS Oxygen saturation of arterial blood (SaO2%) decreased in the three trials compared with baseline. Two hours post-exercise, the SaO2% was high in CHO + Gln condition compared with placebo. Two hours after exercise, interleukin (IL)-1β decreased compared with post-exercise in placebo and was lower compared with baseline in the CHO + Gln condition. Tumor necrosis factor-α decreased 2 h after exercise compared with baseline and pre-exercise in the CHO + Gln condition. No changes were observed in myeloperoxidase or IL-6 production. Two hours after exercise, Gln decreased compared with baseline and post-exercise in placebo and decreased 2 h after exercise in relation to post-exercise in the CHO condition. Gln increased post-exercise compared with pre-exercise in the CHO + Gln condition. Although erythropoietin did not change in this condition, it was high post-exercise and 2 h after exercise in the placebo condition compared with baseline and 2 h after exercise compared with baseline and pre-exercise in the CHO condition. CONCLUSIONS Gln supplementation for 6 d before exercise, associated with CHO supplementation during exercise, was able to revert Gln reduction after exercise and after 2 h of recovery and may have contributed to reducing tumor necrosis factor-α production, suggesting a possible anti-inflammatory effect of supplementation.
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Acute Effects of Interset Rest Duration on Physiological and Perceptual Responses to Resistance Exercise in Hypoxia.
Lockhart, C, Scott, BR, Thoseby, B, Dascombe, BJ
Journal of strength and conditioning research. 2020;(8):2241-2249
Abstract
Lockhart, C, Scott, BR, Thoseby, B, and Dascombe, BJ. Acute effects of interset rest duration on physiological and perceptual responses to resistance exercise in hypoxia. J Strength Cond Res 34(8): 2241-2249, 2020-This study aimed to determine whether manipulating interset rest periods during resistance training in hypoxia impacts on physiological and perceptual responses to exercise. Twelve healthy males completed 1 repetition maximum (1RM) testing for the bilateral leg extension, before completing 4 separate randomized trials comprising 5 × 10 repetitions of leg extensions at 70% 1RM. Experimental trials were completed in both moderate hypoxia (FIO2 = 15%) and normoxia (FIO2 = 21%), using interset rest periods of both 60 and 180 seconds for each environmental condition. Near-infrared spectroscopy was used to quantify muscle oxygenation of vastus lateralis , and surface electromyography assessed the activation of vastus lateralis and medialis. Blood lactate concentration ([BLa]) and midthigh circumference were assessed before and immediately after each trial. Heart rate (HR) responses, blood oxygen saturation, and rating of perceived exertion (RPE) were also assessed after each set and the whole session RPE (sRPE). Perceived quadriceps soreness was reported before, immediately after, and at 24 and 48 hours after each trial. Muscle activation (sets 4-5), RPE (sets 3-5), and sRPE were significantly (p < 0.05) higher in the 60-second trials of the resistance exercise protocol. Significant increases (p < 0.01) were observed for [BLa] and midthigh circumference across sets within each condition. No significant main effect was observed for interset rest duration or environmental condition for muscle oxygenation, HR, or perceived quadriceps soreness. These findings indicate that performing resistance exercise in hypoxia or normoxia with shortened interset rest periods increases muscle activation and perceived exertion, without exacerbating muscle soreness.
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Intermittent Hypoxic Exposure with High Dose of Arginine Impact on Circulating Mediators of Tissue Regeneration.
Zembron-Lacny, A, Gramacki, A, Wawrzyniak-Gramacka, E, Tylutka, A, Hertmanowska, N, Kasperska, A, Czuba, M
Nutrients. 2020;(7)
Abstract
Intermittent exposure to hypoxia (IHE) increases production of reactive oxygen and nitrogen species which, as signalling molecules, participate in tissue injury-repair-regeneration cascade. The process is also stimulated by arginine whose bioavailability is a limiting factor for NO synthesis. The effects of IHE in combination with arginine (Arg) intake on myogenesis and angiogenesis mediators were examined in a randomized and placebo-controlled trial. Blood samples were collected from 38 elite athletes on the 1st, 7th and 14th days during the training camp. The oral doses of arginine (2 × 6 g/day) and/or IHE using hypoxicator GO2Altitude (IHE and Arg/IHE) were applied. Serum NO and H2O2 concentrations increased significantly and were related to muscle damage (CK activity >900 IU/mL) in IHE and Arg/IHE compared to placebo. The changes in NO and H2O2 elevated the levels of circulating growth factors such as HGF, IHG-1, PDGFBB, BDNF, VEGF and EPO. Modification of the lipid profile, especially reduced non-HDL, was an additional beneficial effect of hypoxic exposure with arginine intake. Intermittent hypoxic exposure combined with high-dose arginine intake was demonstrated to affect circulating mediators of injury-repair-regeneration. Therefore, a combination of IHE and arginine seems to be a potential therapeutic and non-pharmacological method to modulate the myogenesis and angiogenesis in elite athletes.
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Investigating Effects of Cold Water Hand Immersion on Selective Attention in Normobaric Hypoxia.
Gerhart, HD, Seo, Y, Kim, JH, Followay, B, Vaughan, J, Quinn, T, Gunstad, J, Glickman, EL
International journal of environmental research and public health. 2019;(16)
Abstract
This study investigated the effect of cold-water hand immersion on selective attention as measured by the Stroop Color Word Test in nomorbaric normoxia and hypoxia. Ten healthy men rested for 60 min, after which they immersed their non-dominant hand into 5 °C water for 15 min. The interference score of the Stroop Color Word Test and thermal sensation were measured at baseline in the final 5 min of resting and in the final 5 min of cold water hand immersion. The interference score was not influenced by hypoxia but was found to be significantly improved compared to resting in both conditions during cold water hand immersion. Selective attention improved during 15 min of cold-water hand immersion, with increased thermal sensations rated as "very cool" of the immersed arm. Cold-water hand immersion may be helpful in improving cognitive function in normoxia and normobaric hypoxia.
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Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia.
Bailey, DM, Rasmussen, P, Overgaard, M, Evans, KA, Bohm, AM, Seifert, T, Brassard, P, Zaar, M, Nielsen, HB, Raven, PB, et al
Circulation. 2017;(2):166-176
Abstract
BACKGROUND The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish their relative contribution in vivo, we quantified arterial-venous concentration gradients across the human cerebral and femoral circulation at rest and during exercise, an ideal model system characterized by physiological extremes of O2 tension and blood flow. METHODS Ten healthy participants (5 men, 5 women) aged 24±4 (mean±SD) years old were randomly assigned to a normoxic (21% O2) and hypoxic (10% O2) trial with measurements performed at rest and after 30 minutes of cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled simultaneously from the brachial artery and internal jugular and femoral veins with plasma and RBC nitric oxide metabolites measured by tri-iodide reductive chemiluminescence. Blood flow was determined by transcranial Doppler ultrasound (cerebral blood flow) and constant infusion thermodilution (femoral blood flow) with net exchange calculated via the Fick principle. RESULTS Hypoxia was associated with a mild increase in both cerebral blood flow and femoral blood flow (P<0.05 versus normoxia) with further, more pronounced increases observed in femoral blood flow during exercise (P<0.05 versus rest) in proportion to the reduction in RBC oxygenation (r=0.680-0.769, P<0.001). Plasma gradients reflecting consumption (arterial>venous; P<0.05) were accompanied by RBC iron nitrosylhemoglobin formation (venous>arterial; P<0.05) at rest in normoxia, during hypoxia (P<0.05 versus normoxia), and especially during exercise (P<0.05 versus rest), with the most pronounced gradients observed across the bioenergetically more active, hypoxemic, and acidotic femoral circulation (P<0.05 versus cerebral). In contrast, we failed to observe any gradients consistent with RBC SNO-Hb consumption and corresponding delivery of plasma S-nitrosothiols (P>0.05). CONCLUSIONS These findings suggest that hypoxia and, to a far greater extent, exercise independently promote arterial-venous delivery gradients of intravascular nitric oxide, with deoxyhemoglobin-mediated reduction identified as the dominant mechanism underlying hypoxic vasodilation.