Altitude Acclimatization Research Articles

Effectiveness of the hypoxic exercise test to predict altitude illness and performance at moderate altitude in high-level swimmers.

PurposeThe hypoxic exercise test is used to predict the susceptibility to severe High Altitude Illness (SHAI). In the present study, we aimed to use this test to predict the changes in performance and the physiological responses to moderate altitude in elite swimmers.MethodsEighteen elite swimmers performed a hypoxic exercise test at sea level before a moderate 12‐day altitude training camp (1,850 m) to determine if they were susceptible or not to SHAI. A maximal swimming performance test was conducted before (at sea level), during (at 1,850 m), and after (at sea level) the intervention. Arterial oxygen saturation (pulse oximetry), Lake Louise score, and quality of sleep questionnaire were collected every morning. The participants were classified in two groups, those who had a moderate to high risk of SHAI (SHAIscore ≥ 3) and those who had a low risk of SHAI (SHAIscore < 3).ResultsSeven swimmers presented a high risk of SHAI including three of them with a SHAIscore > 5. Pearson correlations indicated that SHAIscore was strongly correlated with the decrease in swimming performance at altitude (r = .60, p < .01). Arterial oxygen saturation during the hypoxic exercise test was the physiological variable that was best related to performance decrease at altitude (r = .54, p < .05). No differences were observed for Lake Louise score and quality of sleep between swimmers who suffered from SHAI or not (p > .1).ConclusionIn a population of elite swimmers, the combination of clinical and physiological variables (SHAIscore, oxygen desaturation) estimated the performance decrease at moderate altitude. The hypoxic exercise test could allow coaches and scientists to better determine the individual response of their athletes and manage the altitude acclimatization.

Ventilatory acclimatization to hypoxia: Time to express a critical central message.

Ventilatory acclimatization to hypoxia: Time to express a critical central message.

Marked and rapid effects of pharmacological HIF-2α antagonism on hypoxic ventilatory control.

Hypoxia-inducible factor (HIF) is strikingly upregulated in many types of cancer, and there is great interest in applying inhibitors of HIF as anticancer therapeutics. The most advanced of these are small molecules that target the HIF-2 isoform through binding the PAS-B domain of HIF-2α. These molecules are undergoing clinical trials with promising results in renal and other cancers where HIF-2 is considered to be driving growth. Nevertheless, a central question remains as to whether such inhibitors affect physiological responses to hypoxia at relevant doses. Here, we show that pharmacological HIF-2α inhibition with PT2385, at doses similar to those reported to inhibit tumor growth, rapidly impaired ventilatory responses to hypoxia, abrogating both ventilatory acclimatization and carotid body cell proliferative responses to sustained hypoxia. Mice carrying a HIF-2α PAS-B S305M mutation that disrupts PT2385 binding, but not dimerization with HIF-1β, did not respond to PT2385, indicating that these effects are on-target. Furthermore, the finding of a hypomorphic ventilatory phenotype in untreated HIF-2α S305M mutant mice suggests a function for the HIF-2α PAS-B domain beyond heterodimerization with HIF-1β. Although PT2385 was well tolerated, the findings indicate the need for caution in patients who are dependent on hypoxic ventilatory drive.

Mechanism of sphingosine 1-phosphate clearance from blood.

The interplay of sphingosine 1-phosphate (S1P) synthetic and degradative enzymes as well as S1P exporters creates concentration gradients that are a fundamental to S1P biology. Extracellular S1P levels, such as in blood and lymph, are high relative to cellular S1P. The blood-tissue S1P gradient maintains endothelial integrity while local S1P gradients influence immune cell positioning. Indeed, the importance of S1P gradients was recognized initially when the mechanism of action of an S1P receptor agonist used as a medicine for multiple sclerosis was revealed to be inhibition of T-lymphocytes’ recognition of the high S1P in efferent lymph. Furthermore, the increase in erythrocyte S1P in response to hypoxia influences oxygen delivery during high altitude acclimatization. However, understanding of how S1P gradients are maintained is incomplete. For example, S1P is synthesized but is only slowly metabolized by blood yet circulating S1P turns over quickly by an unknown mechanism. Prompted by the counterintuitive observation that blood S1P increases markedly in response to inhibition S1P synthesis (by sphingosine kinase 2 (SphK2)), we studied mice wherein several tissues were made deficient in either SphK2 or S1P degrading enzymes. Our data reveal a mechanism whereby S1P is de-phosphorylated at the hepatocyte surface and the resulting sphingosine is sequestered by SphK phosphorylation and in turn degraded by intracellular S1P lyase. Thus, we identify the liver as the primary site of blood S1P clearance and provide an explanation for the role of SphK2 in this process. Our discovery suggests a general mechanism whereby S1P gradients are shaped.

Association of EPAS1 and PPARA Gene Polymorphisms with High-Altitude Headache in Chinese Han Population.

Background High-altitude headache (HAH) is the most common complication after high-altitude exposure. Hypoxia-inducible factor- (HIF-) related genes have been confirmed to contribute to high-altitude acclimatization. We aim to investigate a possible association between HIF-related genes and HAH in the Chinese Han population. Methods In total, 580 healthy Chinese Han volunteers were recruited in Chengdu (500 m) and carried to Lhasa (3700 m) by plane in 2 hours. HAH scores and basic physiological parameters were collected within 18–24 hours after the arrival. Thirty-five single nucleotide polymorphisms (SNPs) in HIF-related genes were genotyped, and linkage disequilibrium (LD) was evaluated by Haploview software. The functions of SNPs/haplotypes for HAH were developed by using logistic regression analysis. Results In comparison with wild types, the rs4953354 “G” allele (P=0.013), rs6756667 “A” allele (P=0.013), rs6756667 “A” allele (EPAS1, and rs6520015 “C” allele in PPARA (P=0.013), rs6756667 “A” allele (PPARA (P=0.013), rs6756667 “A” allele (EPAS1, and rs6520015 “C” allele in PPARA (P=0.013), rs6756667 “A” allele (Conclusions EPAS1 and PPARA polymorphisms were associated with HAH in the Chinese Han population. Our findings pointed out potentially predictive gene markers, provided new insights into understanding pathogenesis, and may further provide prophylaxis and treatment strategies for HAH.EPAS1, and rs6520015 “C” allele in PPARA (

CrossTalk proposal: Barometric pressure, independent of , is the forgotten parameter in altitude physiology and mountain medicine

CrossTalk proposal: Barometric pressure, independent of , is the forgotten parameter in altitude physiology and mountain medicine

CrossTalk opposing view: Barometric pressure, independent of , is not the forgotten parameter in altitude physiology and mountain medicine.

CrossTalk opposing view: Barometric pressure, independent of , is not the forgotten parameter in altitude physiology and mountain medicine.

Intraocular pressure and axial length changes during altitude acclimatization from Beijing to Lhasa.

PurposeTo investigate changes in intraocular pressure (IOP) and axial length (AL) on the ascent to high altitude from Beijing to Lhasa.Patients and methodsTwenty volunteers (17 men, 3 women) who had been sent to work in Lhasa, Tibet for more than 6 months were enrolled. One of their journeys from Beijing to Lhasa was chosen as the time for the examination. IOP, AL, corneal curvature (K), and blood pressure (BP) were measured in Beijing (altitude 43 m) and Lhasa (altitude 3658 m). Their first examination was conducted at least 1 day before arriving in Lhasa and the second examination after they had stayed in Lhasa for 7 days. The data from the highland and lowland examinations were analyzed with a paired-sample T test and Pearson’s correlation coefficient was calculated for the association between IOP and average BP.ResultsThe mean IOP was 12.65±2.34 mmHg in Beijing and 14.85±3.1 mmHg in Lhasa. The mean AL was 24.61±1.50mm in Beijing, and 24.98±1.45 mm in Lhasa. The IOP and AL showed a significant elevation in highland compared with lowland (P<0.05). The mean K was 43.58±2.25 D in Beijing and 43.56±2.21 D in Lhasa and no significant difference was found in this study (P>0.05). A positive correlation between variance of IOP and ACD was found (r = 0.475, P<0.05) and no correlation between IOP and average BP was noted.ConclusionsHigh altitude may lead to a small but significant change in IOP and axial length. However, the shape of the corneal surface was not influenced by the hypobaric and hypoxic conditions.

&amp;lt;I&amp;gt;ACTN3&amp;lt;/I&amp;gt; R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude

Introduction: High altitude acclimatization is a process that involve several physiological adjustments, which may increase glucose metabolism because of acute hypoxic exposure. Native highlanders like Tibetans show an increased anaerobic glucose metabolism and a higher proportion of type I muscle fiber than lowlanders. Actin filaments are anchored to the Z line of the sarcomere by a protein called alpha-actinin that exist in two isoforms in the muscle (ACTN2 and ACTN3), however ACTN3 is present only in type II fibers, especially in type IIx. Homozygous individuals for a 577X polymorphism in the ACTN3 gene do not express ACTN3 and seem to be more type I muscle fiber than homozygous individuals 577R. The aim of this study was to compare the glucose consumption response of individuals with different ACTN3 genotypes at simulated 4,500 m altitude. Materials & Methods: Twenty-three volunteers spent four hours exposed to a simulated altitude of 4,500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2 and heart rate were analyzed immediately before entering the chamber and at each hour during the exposure. Results: Glucose after four hours of exposure to hypoxia was different between groups, with RX (68.1 ± 11.7 mg/dl) and RR (71.7 ± 14.4 mg/dl) showing a decreased blood glucose compared to XX (88.7 ± 14.1 mg/dl), indicating an increased dependence on glucose metabolism in individuals with at least one R allele after exposure at 4,500 m simulated altitude. Conclusions: We concluded that individuals with at least one R allele of the ACTN3 R577X gene polymorphism consume more glucose than the ones with XX genotype.

High Altitude as an Environmental Economic Good: Estimating Its Economic Value Using Willingness to Incur Costs by Athletes

High altitude training provides acclimatization to athletes by enhancing endurance; however, this environmental service has remained unaccounted and un-priced. Therefore, this study sought to estimate economic value of high altitude services to athletes using travel cost valuation approach. This study was carried out at Iten Township in Elgeyo Marakwet County, Kenya. Systematic simple random sampling technique was used in administering 223 structured questionnaires to respondents. Excel and Statistical Package for Social Sciences (SPSS version-20) were used for data analysis. Findings from the study showed that athletes incurred estimated cost of about $9.59 per day to train at high altitude, while high altitude attributes such as experience, safety and altitude acclimatization were highly ranked as motivating factors by athletes to train in the study area. Results from statistical tests revealed that experience, age of athletes, safety and altitude effects were significantly difference in influencing athletes’ willingness to incur extra cost for altitude acclimatization. Analysis from logit model showed that experience, age of athletes, safety and altitude effects had high probability to influence athletes to train at high altitude areas. However, stochastic variable in the model showed significant difference in influencing willingness to incur cost by athletes while training at high altitude. This error term explains unobserved variables in the model which were beyond the scope of this study. In conclusion athletes are willing to incur travelling and living costs to train at high altitude areas in order to gain incremental altitude training effects as affirmed by bootstrap hypothesis testing results. Significant of this study will inform policy and decision makers on critical information while they develop sustainable infrastructure, legislation and policies for sports industry.

Saliva panel of protein candidates: A comprehensive study for assessing high altitude acclimatization

Altitude acclimatization describes the processes whereby lowland humans respond to decreased partial pressure of oxygen. It refers to the changes seen as beneficial and involves a series of physiological adjustments that compensate for reduced ambient PO2, as opposed to changes that are pathological. Although numerous reports document the physiological effects of exposure to hypobaric hypoxia of varying durations but an interesting aspect overlooked by many researchers is that of acclimatization related studies. As proteome, a dynamic entity responds immediately to external stimuli, protein markers and their trends can be studied to assess acclimatization status of an individual. Compared to blood, the use of saliva is advantageous because sample collection and processing are easy, minimally invasive, low cost and better tolerated by individuals. In this study, we employed iTRAQ based LC-MS/MS technique for comparing saliva samples from humans exposed to hypobaric hypoxia from 7 to 120 days with normoxic controls followed by analysis using Ingenuity Pathway Analysis software and validation by immunoassays. Nearly 67 proteins were found to be differentially expressed in the exposed groups as compared to normoxia indicating modulated canonical pathways as lipid metabolism; acute phase response signalling and proteins as carbonic anhydrase 6, alpha-enolase, albumin, and prolactin inducible protein. Collectively, this study provides the proof of concept for the non-invasive assessment of high altitude acclimatization.

Cerebral oxygen sensing and the integrated regulation of hypoxic vasodilatation.

Cerebral oxygen sensing and the integrated regulation of hypoxic vasodilatation.

Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.

Despite the prevalence of CO2 retention in human disease, little is known about the adaptive neurobiological effects of chronic hypercapnia. We have recently shown 30-d exposure to increased inspired CO2 (InCO2) leads to a steady-state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO2/H+ chemoreflex, suggesting plasticity within respiratory control centers. Based on data showing brainstem changes in aminergic and inflammatory signaling during carotid body denervation-induced hypercapnia, we hypothesized chronic hypercapnia per se will lead to similar changes. We found that: 1) increased InCO2 increased IL-1β in the medullary raphe (MR), ventral respiratory column, and cuneate nucleus after 24 h, but not after 30 d of hypercapnia; 2) the number of serotonergic and total neurons were reduced within the MR and ventrolateral medulla following 30 d of increased InCO2; 3) markers of tryptophan metabolism were altered following 24 h, but not 30 d of InCO2; and 4) there were few changes in brainstem amine levels following 24 h or 30 d of increased InCO2. We conclude that these changes may contribute to initiating or maintaining respiratory neuroplasticity during chronic hypercapnia but alone do not account for ventilatory acclimatization to chronic increased InCO2.-Burgraff, N. J., Neumueller, S. E., Buchholz, K. J., LeClaire, J., Hodges, M. R., Pan, L., Forster, H. V. Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.

DNA Methylation Changes Are Associated With an Incremental Ascent to High Altitude.

Genetic and nongenetic factors are involved in the individual ability to physiologically acclimatize to high-altitude hypoxia through processes that include increased heart rate and ventilation. High-altitude acclimatization is thought to have a genetic component, yet it is unclear if other factors, such as epigenetic gene regulation, are involved in acclimatization to high-altitude hypoxia in nonacclimatized individuals. We collected saliva samples from a group of healthy adults of European ancestry (n = 21) in Kathmandu (1,400 m; baseline) and three altitudes during a trek to the Everest Base Camp: Namche (3,440 m; day 3), Pheriche (4,240 m; day 7), and Gorak Shep (5,160 m; day 10). We used quantitative bisulfite pyrosequencing to determine changes in DNA methylation, a well-studied epigenetic marker, in LINE-1, EPAS1, EPO, PPARa, and RXRa. We found significantly lower DNA methylation between baseline (1,400 m) and high altitudes in LINE-1, EPO (at 4,240 m only), and RXRa. We found increased methylation in EPAS1 (at 4,240 m only) and PPARa. We also found positive associations between EPO methylation and systolic blood pressure and RXRa methylation and hemoglobin. Our results show that incremental exposure to hypoxia can affect the epigenome. Changes to the epigenome, in turn, could underlie the process of altitude acclimatization.

New metric of hypoxic dose predicts altitude acclimatization status following various ascent profiles.

Medical personnel need practical guidelines on how to construct high altitude ascents to induce altitude acclimatization and avoid acute mountain sickness (AMS) following the first night of sleep at high altitude. Using multiple logistic regression and a comprehensive database, we developed a quantitative prediction model using ascent profile as the independent variable and altitude acclimatization status as the dependent variable from 188 volunteers (147 men, 41 women) who underwent various ascent profiles to 4 km. The accumulated altitude exposure (AAE), a new metric of hypoxic dose, was defined as the ascent profile and was calculated by multiplying the altitude elevation (km) by the number of days (d) at that altitude prior to ascent to 4 km. Altitude acclimatization status was defined as the likely presence or absence of AMS after ~24 h of exposure at 4 km. AMS was assessed using the Cerebral Factor Score (AMS‐C) from the Environmental Symptoms Questionnaire and deemed present if AMS‐C was ≥0.7. Other predictor variables included in the model were age and body mass index (BMI). Sex, race, and smoking status were considered in model development but eliminated due to inadequate numbers in each of the ascent profiles. The AAE (km·d) significantly (P < 0.0001) predicted AMS in the model. For every 1 km·d increase in AAE, the odds of getting sick decreased by 41.3%. Equivalently, for every 1 km·d decrease in AAE, the odds of getting sick increased by 70.4%. Age and BMI were not significant predictors. The model demonstrated excellent discrimination (AUC = 0.83 (95% CI = 0.79–0.91) and calibration (Hosmer‐Lemeshow = 0.11). The model provides a priori estimates of altitude acclimatization status resulting from the use of various rapid, staged, and graded ascent profiles.

UBC-Nepal Expedition: Haemoconcentration underlies the reductions in cerebral blood flow observed during acclimatization to high altitude.

What is the central question of this study? The aim was to evaluate the degree to which increases in haematocrit alter cerebral blood flow and cerebral oxygen delivery during acclimatization to high altitude. What is the main finding and its importance? Through haemodilution, we determined that, after 1week of acclimatization, the primary mechanism contributing to the cerebral blood flow response during acclimatization is an increase in haemoglobin and haematocrit. The remaining contribution to the cerebral blood flow response during acclimatization is likely to be attributable to ventilatory acclimatization. At high altitude, an increase in haematocrit (Hct) is achieved through altitude-induced diuresis and erythropoiesis, both of which result in increased arterial oxygen content. Given the impact of alterations in Hct on oxygen content, haemoconcentration has been hypothesized to mediate, in part, the attenuation of the initial elevation in cerebral blood flow (CBF) at high altitude. To test this hypothesis, healthy men (n=13) ascended to 5050m over 9days without the aid of prophylactic acclimatization medications. After 1week of acclimatization at 5050m, participants were haemodiluted by rapid saline infusion (2.10±0.28l) to return Hct towards pre-acclimatization values. Arterial blood gases, Hct, global CBF (duplex ultrasound) and haemodynamic variables were measured after initial arrival at 5050m and after 1week of acclimatization at high altitude, before and after the haemodilution protocol. After 1week at 5050m, the Hct increased from 42.5±2.5 to 49.6±2.5% (P<0.001), and it was subsequently reduced to 45.6±2.3% (P<0.001) after haemodilution. Global CBF decreased from 844±160 to 619±136mlmin-1 (P=0.033) after 1week of acclimatization and increased to 714±204mlmin -1 (P=0.045) after haemodilution. Despite the significant changes in Hct, and thus oxygen content, cerebral oxygen delivery was unchanged at all time points. Furthermore, these observations occurred in the absence of any changes in mean arterial blood pressure, cardiac output, arterial blood pH or oxygen saturation pre- and posthaemodilution. These data highlight the influence of Hct in the regulation of CBF and are the first to demonstrate experimentally that haemoconcentration contributes to the reduction in CBF during acclimatization to altitude.

High-Altitude Acclimatization Improves Recovery from Muscle Fatigue.

We investigated the effect of high-altitude acclimatization on peripheral fatigue compared with sea level and acute hypoxia. At sea level (350 m), acute hypoxia (environmental chamber), and chronic hypoxia (5050 m, 5-9 d) (partial pressure of inspired oxygen = 140, 74 and 76 mm Hg, respectively), 12 participants (11 in chronic hypoxia) had the quadriceps of their dominant leg fatigued by three bouts of 75 intermittent electrically evoked contractions (12 pulses at 15 Hz, 1.6 s between train onsets, and 15 s between bouts). The initial peak force was ~30% of maximal voluntary force. Recovery was assessed by single trains at 1, 2, and 3 min postprotocol. Tissue oxygenation of rectus femoris was recorded by near-infrared spectroscopy. At the end of the fatigue protocol, the impairments of peak force and peak rates of force development and relaxation were greater (all P < 0.05) in acute hypoxia (~51%, 53%, and 64%, respectively) than sea level (~43%, 43%, and 52%) and chronic hypoxia (~38%, 35%, and 48%). Peak force and rate of force development recovered faster (P < 0.05) in chronic hypoxia (pooled data for 1-3 min: ~84% and 74% baseline, respectively) compared with sea level (~73% and 63% baseline) and acute hypoxia (~70% and 55% baseline). Tissue oxygenation did not differ among conditions for fatigue or recovery (P > 0.05). Muscle adaptations occurring with chronic hypoxia, independent of other adaptations, positively influence muscle contractility during and after repeated contractions at high altitude.

Effect Of Intermittent Hypoxic Exercise Training On Improving Altitude Acclimatization

Effect Of Intermittent Hypoxic Exercise Training On Improving Altitude Acclimatization

Biological Variation of Resting Ventilation and its Diagnostic Accuracy for Acute Mountain Sickness at Altitude

Individuals who develop acute mountain sickness (AMS) upon exposure to high altitude (HA) exhibit differential responses in resting measures of minute ventilation (VE) and end-tidal partial pressure of carbon dioxide (PETCO2). PURPOSE: To determine the biological variation and diagnostic potential of ventilatory parameters in association with AMS. METHODS: We performed a retrospective analysis via the Mountain Medicine Database of 22 studies completed by the U.S. Army Research Institute of Environmental Medicine (N = 424). First, we determined the biological variation of resting measures of ventilation and defined the accompanying static and dynamic thresholds that indicate a significant deviation from normal at sea level (SL). Second, the diagnostic accuracy of ventilatory measures for AMS development was assessed at HA (4300 m). RESULTS: Resting measures of ventilation demonstrated substantial variability within (range 0.4 - 7.7%) and between (range 1.0 - 24.5%) subjects. Based on the index of individuality (II), end-tidal partial pressure of oxygen (PETO2) and respiratory exchange ratio (RER) may be useful in the static assessment of physiological deviations from normal (II = 0.57 and 0.60, respectively) at HA. Based on the index of heterogeneity (IH), PETO2 and peripheral oxygen saturation (SpO2) may be useful in the dynamic assessment of deviations from normal (IH = 1.91 and 0.41, respectively) at HA. RER and SpO2 showed significant diagnostic accuracy in the static assessment of AMS (sensitivity/specificity = 53/86 and 24/96, respectively). Ventilatory efficiency for oxygen (VE/VO2), RER, and SpO2 showed significant diagnostic accuracy in the dynamic assessment of AMS (sensitivity/specificity = 72/54, 53/74, and 25/98, respectively). Among all measures, RER showed the greatest Youden’s Index, a value indicative of the combined sensitivity and specificity of a given predictor (static: 39, dynamic: 28). CONCLUSION: Many resting ventilation measures do not demonstrate potential for AMS prediction. However, the few measures identified as potential predictors of AMS following SL biological variation analysis also demonstrated the greatest diagnostic power for AMS at HA. RER shows particular promise as a potential AMS prediction tool. DISCLAIMER: Author views not official US Army or DOD policy.

Intermittent normobaric hypoxia facilitates high altitude acclimatization by curtailing hypoxia-induced inflammation and dyslipidemia.

Intermittent hypoxic training (IHT) is a discrete cost-effective method for improving athletic performance and high altitude acclimatization. Unfortunately, IHT protocols widely vary in terms of hypoxia severity, duration, and number of cycles affecting physiological outcomes. In the present study, we evaluated the efficacy of a moderate normobaric IHT protocol (12% FiO2 for 4h, 4days) on acclimatization to high altitude (3250m). Global plasma proteomics studies revealed that IHT elicited acute-phase response proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and alpha-1-acid glycoprotein 2 (AGP 2) as well as altered levels of several apolipoproteins. On subsequent exposure to high altitude, the IH trained volunteers exhibited significant higher arterial oxygen saturation with concomitant lower incidences of acute mountain sickness (AMS) as compared to controls. Interestingly, IH trained subjects exhibited lower levels of positive acute-phase proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and fibrinogen (FGA, FGB, and FGG) both after days 4 and 7 of high altitude ascent. High altitude exposure also decreased the levels of HDL, LDL, and associated proteins as well as key enzymes for assembly and maturation of lipoprotein particles like lecithin-cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). In contrast, IHT curtailed hypoxia-induced alterations of HDL, LDL, Apo-AI, Apo-B, LCAT, CETP, and PLTP. Further validation of results also corroborated attenuation of hypoxia-induced inflammation and dyslipidemia by IHT. These results provide molecular evidences supporting the use of moderate IHT as a potential non-pharmacological strategy for high altitude acclimatization.