High-Throughput Griess Assay of Nitrite and Nitrate in Plasma and Red Blood Cells for Human Physiology Studies under Extreme Conditions.

The metabolism of nitric oxide plays an increasingly interesting role in the physiological response of the human body to extreme environmental conditions, such as underwater, in an extremely cold climate, and at low oxygen concentrations. Field studies need the development of analytical methods to measure nitrite and nitrate in plasma and red blood cells with high requirements of accuracy, precision, and sensitivity. An optimized spectrophotometric Griess method for nitrite-nitrate affords sensitivity in the low millimolar range and precision within ±2 µM for both nitrite and nitrate, requiring 100 µL of scarcely available plasma sample or less than 50 µL of red blood cells. A scheduled time-efficient procedure affords measurement of as many as 80 blood samples, with combined nitrite and nitrate measurement in plasma and red blood cells. Performance and usefulness were tested in pilot studies that use blood fractions deriving from subjects who dwelt in an Antarctica scientific station and on breath-holding and scuba divers who performed training at sea and in a land-based deep pool facility. The method demonstrated adequate to measure low basal concentrations of nitrite and high production of nitrate as a consequence of water column pressure-triggered vasodilatation in deep-water divers.

Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.

Marching to the Beet: The effect of dietary nitrate supplementation on high altitude exercise performance and adaptation during a military trekking expedition.

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.

Impact of baseline serum ferritin and supplemental iron on altitude-induced hemoglobin mass response in elite athletes.

The present study explored the impact of pre-altitude serum (s)-ferritin and iron supplementation on changes in hemoglobin mass (ΔHbmass) following altitude training. Measures of Hbmass and s-ferritin from 107 altitude sojourns (9-28 days at 1800-2500 m) with world-class endurance athletes (males n = 41, females n = 25) were analyzed together with iron supplementation and self-reported illness. Altitude sojourns with a hypoxic dose [median (range)] of 1169 (912) km·h increased Hbmass (mean ± SD) 36 ± 38 g (3.7 ± 3.7%, p < 0.001) and decreased s-ferritin -11 (190) µg·L-1 (p = 0.001). Iron supplements [27 (191) mg·day-1 ] were used at 45 sojourns (42%), while only 11 sojourns (10%) were commenced with s-ferritin <35 µg/L. Hbmass increased by 4.6 ± 3.7%, 3.4 ± 3.3%, 4.2 ± 4.3%, and 2.9 ± 3.4% with pre-altitude s-ferritin ≤35 µg·L-1 , 36-50 µg·L-1 , 51-100 µg·L-1 , and >100 µg·L-1 , respectively, with no group difference (p = 0.400). Hbmass increased by 4.1 ± 3.9%, 3.0 ± 3.0% and 3.7 ± 4.7% without, ≤50 mg·day-1 or >50 mg·day-1 supplemental iron, respectively (p = 0.399). Linear mixed model analysis revealed no interaction between pre-altitude s-ferritin and iron supplementation on ΔHbmass (p = 0.906). However, each 100 km·h increase in hypoxic dose augmented ΔHbmass by an additional 0.4% (95% CI: 0.1-0.7%; p = 0.012), while each 1 g·kg-1 higher pre-altitude Hbmass reduced ΔHbmass by -1% (-1.6 to -0.5; p < 0.001), and illness lowered ΔHbmass by -5.7% (-8.3 to -3.1%; p < 0.001). In conclusion, pre-altitude s-ferritin or iron supplementation were not related to the altitude-induced increase in Hbmass (3.7%) in world-class endurance athletes with clinically normal iron stores.

D4F prophylaxis enables redox and energy homeostasis while preventing inflammation during hypoxia exposure.

Apo-A1 is correlated with conditions like hyperlipidemia, cardiovascular diseases, high altitude pulmonary edema and etc. where hypoxia constitutes an important facet.Hypoxia causes oxidative stress, vaso-destructive and inflammatory outcomes.Apo-A1 is reported to have vasoprotective, anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, effects of Apo-A1 augmentation during hypoxia exposure are unknown.In this study, we investigated the effects of exogenously supplementing Apo-A1-mimetic peptide on SD rats during hypoxia exposure. For easing the processes of delivery, absorption and bio-availability, Apo-A1 mimetic peptide D4F was used. The rats were given 10 mg/kg BW dose (i.p.) of D4F for 7 days and then exposed to hypoxia. D4F was observed to attenuate both oxidative stress and inflammation during hypoxic exposure. D4F improved energy homeostasis during hypoxic exposure. D4F did not affect HIF-1a levels during hypoxia but increased MnSOD levels while decreasing CRP and Apo-B levels. D4F showed promise as a prophylactic against hypoxia exposure.

Carbohydrate Supplementation and the Influence of Breakfast on Fuel Use in Hypoxia.

PURPOSE: This study investigated the effect of carbohydrate supplementation on substrate oxidation during exercise in hypoxia after preexercise breakfast consumption and omission. METHODS: Eleven men walked in normobaric hypoxia (FiO2 ~11.7%) for 90 min at 50% of hypoxic V˙O2max. Participants were supplemented with a carbohydrate beverage (1.2 g·min-1 glucose) and a placebo beverage (both enriched with U-13C6 D-glucose) after breakfast consumption and after omission. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate carbohydrate (exogenous and endogenous [muscle and liver]) and fat oxidation. RESULTS: In the first 60 min of exercise, there was no significant change in relative substrate oxidation in the carbohydrate compared with placebo trial after breakfast consumption or omission (both P = 0.99). In the last 30 min of exercise, increased relative carbohydrate oxidation occurred in the carbohydrate compared with placebo trial after breakfast omission (44.0 ± 8.8 vs 28.0 ± 12.3, P < 0.01) but not consumption (51.7 ± 12.3 vs 44.2 ± 10.4, P = 0.38). In the same period, a reduction in relative liver (but not muscle) glucose oxidation was observed in the carbohydrate compared with placebo trials after breakfast consumption (liver, 7.7% ± 1.6% vs 14.8% ± 2.3%, P < 0.01; muscle, 25.4% ± 9.4% vs 29.4% ± 11.1%, P = 0.99) and omission (liver, 3.8% ± 0.8% vs 8.7% ± 2.8%, P < 0.01; muscle, 19.4% ± 7.5% vs 19.2% ± 12.2%, P = 0.99). No significant difference in relative exogenous carbohydrate oxidation was observed between breakfast consumption and omission trials (P = 0.14). CONCLUSION: In acute normobaric hypoxia, carbohydrate supplementation increased relative carbohydrate oxidation during exercise (>60 min) after breakfast omission, but not consumption.

Improving Nocturnal Hypoxemic Burden with Transvenous Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea.

Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep apnea (CSA). The remede System Pivotal Trial population was examined for nocturnal hypoxemic burden. The minutes of sleep with oxygen saturation < 90% significantly improved in Treatment compared with control (p < .001), with the median improving from 33 min at baseline to 14 min at 6 months. Statistically significant improvements were also observed for average oxygen saturation and lowest oxygen saturation. Hypoxemic burden has been demonstrated to be more predictive for mortality than apnea-hypopnea index (AHI) and should be considered a key metric for therapies used to treat CSA. Transvenous phrenic nerve stimulation is capable of delivering meaningful improvements in nocturnal hypoxemic burden. There is increasing interest in endpoints other than apnea-hypopnea index in sleep-disordered breathing. Nocturnal hypoxemia burden may be more predictive for mortality than apnea-hypopnea index in patients with poor cardiac function. Transvenous phrenic nerve stimulation is capable of improving nocturnal hypoxemic burden. Graphical Abstract.

Ascorbate maintains a low plasma oxygen level.

In human blood, oxygen is mainly transported by red blood cells. Accordingly, the dissolved oxygen level in plasma is expected to be limited, although it has not been quantified yet. Here, by developing dedicated methods and tools, we determined that human plasma pO2 = 8.4 mmHg (1.1% O2). Oxygen solubility in plasma was believed to be similar to water. Here we reveal that plasma has an additional ascorbate-dependent oxygen-reduction activity. Plasma experimental oxygenation oxidizes ascorbate (49.5 µM in fresh plasma vs < 2 µM in oxidized plasma) and abolishes this capacity, which is restored by ascorbate supplementation. We confirmed these results in vivo, showing that the plasma pO2 is significantly higher in ascorbate-deficient guinea pigs (Ascorbateplasma < 2 µM), compared to control (Ascorbateplasma > 15 µM). Plasma low oxygen level preserves the integrity of oxidation-sensitive components such as ubiquinol. Circulating leucocytes are well adapted to these conditions, since the abundance of their mitochondrial network is limited. These results shed a new light on the importance of oxygen exposure on leucocyte biological study, in regards with the reducing conditions they encounter in vivo; but also, on the manipulation of blood products to improve their integrity and potentially improve transfusions' efficacy.

No effect of supplemented heat stress during an acute endurance exercise session in hypoxia on hepcidin regulation.

Hepcidin is a novel factor for iron deficiency in athletes, which is suggested to be regulated by interleukin-6 (IL-6) or erythropoietin (EPO). PURPOSE: The purpose of the present study was to compare endurance exercise-induced hepcidin elevation among "normoxia", "hypoxia" and "combined heat and hypoxia". METHODS: Twelve males (21.5 ± 0.3 years, 168.1 ± 1.2 cm, 63.6 ± 2.0 kg) participated in the present study. They performed 60 min of cycling at 60% of [Formula: see text] in either "heat and hypoxia" (HHYP; FiO2 14.5%, 32 °C), "hypoxia" (HYP; FiO2 14.5%, 23 °C) or "normoxia" (NOR; FiO2 20.9%, 23 °C). After completing the exercise, participants remained in the prescribed conditions for 3 h post-exercise. Blood samples were collected before, immediately and 3 h after exercise. RESULTS: Plasma IL-6 level significantly increased immediately after exercise (P < 0.05), with no significant difference among the trials. A significant elevation in serum EPO was observed 3 h after exercise in hypoxic trials (HHYP and HYP, P < 0.05), with no significant difference between HHYP and HYP. Serum hepcidin level increased 3 h after exercise in all trials (NOR, before 18.3 ± 3.9 and post180 31.2 ± 6.3 ng/mL; HYP, before 13.5 ± 2.5 and post180 23.3 ± 3.6 ng/mL, HHYP; before 15.8 ± 3.3 and post180 31.4 ± 5.3 ng/mL, P < 0.05). However, there was no significant difference among the trials during post-exercise. CONCLUSION: Endurance exercise in "combined heat and hypoxia" did not exacerbate exercise-induced hepcidin elevation compared with the same exercise in "hypoxia" or "normoxia".

Therapeutic effects and modulatory mechanism of Alpiniae oxyphyllae Fructus in chronic intermittent hypoxia induced enuresis in rats.

OBJECTIVE: The objective of this study was to explore the effect of Alpiniae oxyphyllae Fructus (AOF) on a rat model of chronic intermittent hypoxia (CIH)-induced enuresis. Findings of this study may help identify therapeutic targets in children with nocturnal enuresis (NE). METHODS: Female rats were randomly divided into a control group (saline gavage, 4 weeks of normal air), CIH group (saline gavage, 4 weeks of CIH), and AOF group (AOF gavage, 4 weeks of CIH). The variables measured in this study included water intake, urine output, bladder leak point pressure (BLPP), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. The expression levels of the purinergic P2X3 receptor, muscarinic M3 receptor, and ß3-adrenergic receptor (ß3-AR) in the bladder were also measured. The bladder was subjected to haematoxylin and eosin (HE) and Weigert staining, and histological changes were observed under a light microscope to evaluate the morphological changes in the bladder in each group. RESULTS: Compared with the control group, urine output was increased, and the BLPP was decreased in the CIH group, but AOF administration decreased urine output and increased BLPP. In addition, the serum MDA level increased and the SOD activity decreased in the CIH group compared with the control group. Administration of AOF decreased the MDA level and increased the SOD activity. Additionally, compared with the control group, HE and Weigert staining in the CIH group showed that the bladder detrusor muscle bundles were disordered and loose, some muscle bundles were broken, the content of collagen fibres in the gap was reduced, and the gap was significantly widened. However, following the administration of AOF, the bladder detrusor muscle bundles were neatly arranged, and the content of collagen fibres in the gap was increased. Furthermore, compared with the control group, the purinergic P2X3 receptor and muscarinic M3 receptor were expressed at higher levels, and ß3-AR was expressed at lower levels in the CIH group, but AOF administration decreased the expression of the purinergic P2X3 receptor and muscarinic M3 receptor and increased the expression of the ß3-AR. CONCLUSIONS: AOF improves enuresis by inhibiting oxidative stress and regulating the expression of the purinergic P2X3 receptor, muscarinic M3 receptor, and ß3 adrenergic receptor.

Appetite and energy intake responses to breakfast consumption and carbohydrate supplementation in hypoxia.

PURPOSE: The purpose of experiment one was to determine the appetite, acylated ghrelin and energy intake response to breakfast consumption and omission in hypoxia and normoxia. Experiment two aimed to determine the appetite, acylated ghrelin and energy intake response to carbohydrate supplementation after both breakfast consumption and omission in hypoxia. METHODS: In experiment one, twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~11.7%) and normoxia. In experiment two, eleven participants rested and exercised in normobaric hypoxia (4300 m: FiO2 ~11.7%), twice after consuming a high carbohydrate breakfast and twice after breakfast omission. Participants consumed both a carbohydrate (1.2g·min-1 glucose) and a placebo beverage after breakfast consumption and omission. Measures of appetite perceptions and acylated ghrelin were taken at regular intervals throughout both experiments and an ad-libitum meal was provided post-exercise to quantify energy intake. RESULTS: Breakfast consumption had no significant effect on post exercise energy intake or acylated ghrelin concentrations, despite reductions in appetite perceptions. As such, breakfast consumption increased total trial energy intake compared with breakfast omission in hypoxia (7136 ± 2047 kJ vs. 5412 ± 1652 kJ; p = 0.02) and normoxia (9276 ± 3058 vs. 6654 ± 2091 kJ; p < 0.01). Carbohydrate supplementation had no effect on appetite perceptions or acylated ghrelin concentrations after breakfast consumption or omission. As such, carbohydrate supplementation increased total energy intake after breakfast consumption (10222 ± 2831 kJ vs. 7695 ± 1970 kJ p < 0.01) and omission (8058 ± 2574 kJ vs. 6174 ± 2222 kJ p = 0.02). CONCLUSION: Both breakfast consumption and carbohydrate supplementation provide beneficial dietary interventions for increasing energy intake in hypoxic conditions.

The association of coffee consumption and oxygen desaturation index during sleep among Japanese male workers.

BACKGROUND AND OBJECTIVE: Coffee is a major caffeine-containing food source that can be used for treatment of apnea in prematurity. However, few studies have examined the association between coffee consumption and sleep-disordered breathing (SDB). We investigated whether coffee consumption is associated with the oxygen desaturation index (ODI) as a marker of SDB among middle-aged Japanese male workers. METHODS: The subjects were 1126 male local government workers aged 22-59 who participated in SDB screening in 2011-2012. Daily coffee consumption was assessed by a self-administered questionnaire. We measured 3% oxygen desaturation (3%ODI) during a night's sleep using a pulse oximeter. A general linear model was used to calculate the multivariate-adjusted means of 3%ODI per quartile of coffee consumption. We further analyzed the data after stratifying by overweight and current smoking status. RESULTS: A inverse association between coffee consumption and 3%ODI was found. The multivariate-adjusted mean of 3%ODI for the lowest and highest coffee consumption groups were 11.9 times/h and 10.6 times/h (p for trend = 0.06), respectively; 14.6 and 11.5 times/h (p for trend = 0.01) in overweight participants; and 12.7 and 11.0 times/h (p for trend = 0.06) in non-smokers. No associations were found in non-overweight and smoking workers. CONCLUSIONS: Our results suggest that higher coffee consumption was associated with lower 3% ODI as a marker of SDB in overweight and non-smoking workers.

Influence of the TLR4-mediated p38MAPK signaling pathway on chronic intermittent hypoxic-induced rat's oxidative stress and inflammatory cytokines in rats.

OBJECTIVE: To investigate the influence of the TOLL-like receptor 4 (TLR4)-mediated p38MAPK signaling pathway on chronic intermittent hypoxic (CIH)-induced oxidative stress and inflammatory cytokines in rats. MATERIALS AND METHODS: A total of 120 healthy male Sprague Dawley (SD) rats, aged between 8-10 weeks, were randomly divided into 9 groups (normoxia control group, CIH 2 weeks group, CIH 4 weeks group, CIH 6 weeks group, CIH 8 weeks group, CIH 6 weeks + p38MAPK receptor inhibit group, CIH 6 weeks + Tempol group, CIH 8 weeks + p38MAPK receptor inhibitor group and CIH 8 weeks + Tempol group). The expression of TLR4 and p38MAPK in the adipose tissue was evaluated, as well as the level of serum oxidative stress markers (SOD, TRx-1, MDA) and inflammatory cytokines (adiponectin, TNF-α, hsCRP and IL-6). RT-PCR and Western-blot were conducted to detect the expression of TLR4 and p38MAPK mRNA. RESULTS: With increased hypoxia, the levels of SOD and adiponectin in the serum of the CIH group decreased significantly, and the levels of TNF-α, hsCRP, IL-8 and IL-6 in serum increased significantly. After the intervention of antioxidant Tempol and p38MAPK inhibitor SB203580, SOD increased significantly but with significant MDA reduction. The levels of TNF-α, hsCRP, IL-8 and IL-6 in serum significantly decreased. The results of RT-PCR and Western-Blot indicated that the P-p38 and TLR4 proteins related to the MAPK pathway were expressed in rat adipose tissue. With the hypoxia intensity, expression of P-p38 decreased after initially increasing. The expression of TLR4 showed a continuously growing trend. After Tempol treatment, the expression of p38MAPK protein decreased, and the expression of TLR4 did not change significantly, indicating the inhibiting effect of Tempol on p38MAPK, without a significant inhibiting effect on TLR4. CONCLUSIONS: The TLR4-mediated p38MAPK signaling pathway was active in adipose tissue and the expression of the corresponding molecules increased as the duration of intermittent hypoxia increased. The expression of TLR4 and p38MAPK components regulated the level of oxidative stress and inflammatory cytokines; the application of p38MAPK inhibitors and antioxidant free radical scavengers improved the levels of oxidative stress and inflammatory cytokines.

Acute dietary nitrate supplementation does not attenuate oxidative stress or the hemodynamic response during submaximal exercise in hypobaric hypoxia.

The purpose of this study was to investigate changes in oxidative stress, arterial oxygen saturation (SaO2), blood pressure (BP), and heart rate (HR) during exercise in hypobaric hypoxia following acute dietary nitrate supplementation. Nine well-trained (maximal oxygen consumption, 60.8 ± 7.8 mL·kg-1·min-1) males (age, 29 ± 7 years) visited the laboratory on 3 occasions, each separated by 1 week. Visit 1 included a maximal aerobic cycling test and five 5-min increasing-intensity exercise bouts in a normobaric environment (1600 m). A single dose of either a nitrate-depleted placebo (PL) or a nitrate-rich beverage (NR; 12.8 mmol nitrate) was consumed 2.5 h prior to exercise during visits 2 and 3 (3500 m) in a double-blind, placebo-controlled, crossover study consisting of a 5-min cycling warm-up and 4 bouts, each 5 min in duration, separated by 4-min periods of passive rest. Exercise wattages were determined during visit 1 and corresponded to 25%, 40%, 50%, 60%, and 70% of normobaric maximal oxygen consumption. Catalase and 8-isoprostane were measured before and after exercise (immediately before and 1 h postexercise, respectively). NR increased plasma nitrite (1.53 ± 0.83 µmol·L-1) compared with PL (0.88 ± 0.56 µmol·L-1) (p < 0.05). In both conditions, postexercise (3500 m) 8-isoprostane (PL, 23.49 ± 3.38 to 60.90 ± 14.95 pg·mL-1; NR, 23.23 ± 4.12 to 52.11 ± 19.76 pg·mL-1) and catalase (PL, 63.89 ± 25.69 to 128.15 ± 41.80 mmol·min-1·mL-1; NR, 78.89 ± 30.95 to 109.96 ± 35.05 mmol·min-1·mL-1) were elevated compared with baseline resting values (p < 0.05). However, both 8-isoprostane and catalase were similar in the 2 groups (PL and NR) (p = 0.217 and p = 0.080, respectively). We concluded that an acute, pre-exercise dose of dietary nitrate yielded no beneficial changes in oxidative stress, SaO2, BP, or HR in healthy, aerobically fit men exercising at 3500 m.

Intravenous Iron Does Not Augment the Hemoglobin Mass Response to Simulated Hypoxia.

PURPOSE: Iron is integral for erythropoietic adaptation to hypoxia, yet the importance of supplementary iron compared with existing stores is poorly understood. The aim of the present study was to compare the magnitude of the hemoglobin mass (Hbmass) in response to altitude in athletes with intravenous (IV), oral, or placebo iron supplementation. METHODS: Thirty-four, nonanemic, endurance-trained athletes completed 3 wk of simulated altitude (3000 m, 14 h·d), receiving two to three bolus iron injections (ferric carboxymaltose), daily oral iron supplementation (ferrous sulfate), or a placebo, commencing 2 wk before and throughout altitude exposure. Hbmass and markers of iron regulation were assessed at baseline (day -14), immediately before (day 0), weekly during (days 8 and 15), and immediately, 1, 3, and 6 wk after (days 22, 28, 42, and 63) the completion of altitude exposure. RESULTS: Hbmass significantly increased after altitude exposure in athletes with IV (mean % [90% confidence interval (CI)], 3.7% [2.8-4.7]) and oral (3.2% [2.2-4.2]) supplementation and remained elevated at 7 d postaltitude in oral (2.9% [1.5-4.3]) and 21 d after in IV (3.0% [1.5-4.6]) supplementation. Hbmass was not significantly higher than baseline at any time point in placebo. CONCLUSIONS: Iron supplementation appears necessary for optimal erythropoietic adaptation to altitude exposure. IV iron supplementation during 3 wk of simulated live high-train low altitude training offered no additional benefit in terms of the magnitude of the erythropoietic response for nonanemic endurance athletes compared with oral supplementation.

"Living High-Training Low" improved weight loss and glucagon-like peptide-1 level in a 4-week weight loss program in adolescents with obesity: A pilot study.

BACKGROUND: "Living High-Training Low" (LHTL) is effective for the improvement of athletic ability; however, little is known about the effect of LHTL on obese individuals. The present study determined whether LHTL would have favorable influence on body composition, rebalance the appetite hormones, and explore the underlying mechanism. METHODS: Adolescents with obesity [body mass index (BMI) >30 kg/m] were randomly assigned to "Living Low-Training Low" (LLTL, n = 19) group that slept in a normobaric normoxia condition and the LHTL (n = 16) group slept in a normobaric hypoxia room (14.7% PO2 ∼2700 m). Both groups underwent the same aerobic exercise training program. Morphological, blood lipids, and appetite hormones were measured and assessed. RESULTS: After the intervention, the body composition improved in both groups, whereas reductions in body weight (BW), BMI, and lean body mass increased significantly in the LHTL group (all, P < .05). In the LLTL group, cholecystokinin (CCK) decreased remarkably (P < .05) and CCK changes were positively associated with changes in BW (r = 0.585, P = .011) and BMI (r = 0.587, P = .010). However, in the LHTL group, changes in plasma glucagon-like peptide-1 (GLP-1) and interleukin-6 (IL-6) levels, positively correlated with each other (r = 0.708, P = .015) but negatively with BW changes (r = -0.608, P = .027 and r = -0.518, P = .048, respectively). CONCLUSION: The results indicated that LHTL could induce more weight loss safely and efficiently as compared to LLTL and increase the plasma GLP-1 levels that may be mediated by IL-6 to rebalance the appetite. Thus, an efficient method to treat obesity and prevent weight regain by appetite rebalance in hypoxia condition was established.

Influence of combined iron supplementation and simulated hypoxia on the haematological module of the athlete biological passport.

The integrity of the athlete biological passport (ABP) is underpinned by understanding normal fluctuations of its biomarkers to environmental or medical conditions, for example, altitude training or iron deficiency. The combined impact of altitude and iron supplementation on the ABP was evaluated in endurance-trained athletes (n = 34) undertaking 3 weeks of simulated live-high: train-low (14 h.d-1 , 3000 m). Athletes received either oral, intravenous (IV) or placebo iron supplementation, commencing 2 weeks prior and continuing throughout hypoxic exposure. Venous blood was sampled twice prior, weekly during, and up to 6 weeks after altitude. Individual ABP thresholds for haemoglobin concentration ([Hb]), reticulocyte percentage (%retic), and OFF score were calculated using the adaptive model and assessed at 99% and 99.9% specificity. Eleven athletes returned values outside of the calculated reference ranges at 99%, with 8 at 99.9%. The percentage of athletes exceeding the thresholds in each group was similar, but IV returned the most individual occurrences. A similar frequency of abnormalities occurred across the 3 biomarkers, with abnormal [Hb] and OFF score values arising mainly during-, and %retic values mainly post- altitude. Removing samples collected during altitude from the model resulted in 10 athletes returning abnormal values at 99% specificity, 2 of whom had not triggered the model previously. In summary, the abnormalities observed in response to iron supplementation and hypoxia were not systematic and mostly in line with expected physiological adaptations. They do not represent a uniform weakness in the ABP. Nevertheless, altitude training and iron supplementation should be carefully considered by experts evaluating abnormal ABP profiles.