Nutrition in Women at High Altitude: A Scoping Review-UIAA Medical Commission Recommendations.

Andjelkovic, Marija, Peter Paal, Susi Kriemler, Kaste Mateikaite-Pipiriene, Alison Rosier, Beth Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, Lenka Horakova, Dominique Jean, and Linda E. Keyes. Nutrition in women at high altitude: a scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 25:9-15, 2024. Background: Nutritional concerns such as food composition, energy intake, and nutrient absorption are essential for performance at high altitude and may differ between men and women. We performed a scoping review to summarize what is currently known on nutrition for women during short-term, high-altitude, physically active sojourns. Methods: The UIAA Medical Commission convened an international team to review women's health issues at high altitude and to publish updated recommendations. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including nutrition, metabolism, energy composition, micronutrients) with additional publications found by hand search. Results: We found 7,165 articles, of which 13 original articles assessed nutritional aspects in physically active women on short-term high-altitude sojourns, with other articles found by hand search. We summarize the main findings. Conclusions: Data on women's nutrition at altitude are very limited. Reduction in energy intake plus increased energy expenditure at high altitude can lead to unbalanced nutrition, negatively influencing high-altitude adaptation and physical performance. Therefore, adequate dietary and fluid intake is essential to maintaining energy balance and hydration at high altitude in women as in men. Iron supplementation should be considered for women with iron depletion before travel.

Menopause and High Altitude: A Scoping Review-UIAA Medical Commission Recommendations.

Mateikaite-Pipiriene, Kaste, Dominique Jean, Peter Paal, Lenka Horakova, Susi Kriemler, Alison J. Rosier, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, and Linda E. Keyes for the UIAA MedCom writing group on Women's Health in the Mountains. Menopause and high altitude: A scoping review-UIAA Medical Commission Recommendations. High Alt Med Biol. 25:1-8, 2024. Background: Older people are an important fraction of mountain travelers and climbers, many of them postmenopausal women. The aim of this work was to review health issues that older and postmenopausal women may experience at high altitude, including susceptibility to high-altitude illness. Methods: We performed a scoping review for the UIAA Medical Commission series on Women's Health in the mountains. We searched PubMed and Cochrane libraries and performed an additional manual search. The primary search focused on articles assessing lowland women sojourning at high altitude. Results: We screened 7,165 potential articles. The search revealed three relevant articles, and the manual search another seven articles and one abstract. Seven assessed menopausal low-altitude residents during a high-altitude sojourn or performing hypoxic tests. Four assessed high-altitude residents. We summarize the results of these 11 studies. Conclusions: Data are limited on the effects of high altitude on postmenopausal women. The effects of short-term, high-altitude exposure on menopause symptoms are unknown. Menopause has minimal effect on the physiological responses to hypoxia in physically fit women and does not increase the risk of acute mountain sickness. Postmenopausal women have an increased risk of urinary tract infections, which may be exacerbated during mountain travel. More research is needed on the physiology and performance of older women at high altitude.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update.

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches for managing each form of acute altitude illness that incorporate these recommendations as well as recommendations on how to approach high altitude travel following COVID-19 infection. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine in 2010 and the subsequently updated WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2014 and 2019.

Women's Health at High Altitude: An Introduction to a 7-Part Series by the International Climbing and Mountaineering Federation Medical Commission.

Horakova, Lenka, Peter Paal, Jacqueline Pichler Hefti, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, David Hillebrandt, Dominique Jean, Kaste Mateikaite-Pipiriene, Alison J. Rosier, Susi Kriemler, and Linda E. Keyes. Women's health at high altitude: An introduction to a 7-part series by the International Climbing and Mountaineering Federation Medical Commission. High Alt Med Biol. 24:243-246, 2023. Background: Women have been traveling to high altitude since the inception of modern mountaineering. Although there are distinct female-specific features such as menstruation and menopause relevant to adaptation to and performance at high altitude, very little data exist on women's high-altitude health. To summarize what is known to date, the Medical Commission of the International Climbing and Mountaineering Federation (UIAA) has created a series of articles on women's health, high altitude illness, and performance at high altitude. Methods: Assembling an international author team, two types of manuscripts were developed: (1) reviews on female-specific topics such as pregnancy; (2) reviews on sex differences in high-altitude related illnesses, nutrition, cold injuries, and mortality. Results: The literature search yielded 7,165 articles, with 482 studies meeting the inclusion criteria for full-text review. The authors of individual chapters reviewed these articles and performed additional hand searches. Conclusions: Some important questions on women sojourning and exercising at high altitude have been studied, but many are still awaiting a qualified and evidence-based response. Our seven reviews, to be published in future issues of this journal, summarize what is known about lowland women sojourning at high altitude, provide recommendations, and highlight knowledge gaps in high altitude women's medicine.

Acute Mountain Sickness and High Altitude Cerebral Edema in Women: A Scoping Review-UIAA Medical Commission Recommendations.

Derstine, Mia, Dominique Jean, Beth A. Beidleman, Jacqueline Pichler Hefti, David Hillebrandt, Lenka Horakova, Susi Kriemler, Kasté Mateikaité-Pipiriené, Peter Paal, Alison Rosier, Marija Andjelkovic, and Linda E. Keyes. Acute mountain sickness and high altitude cerebral edema in women: A scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 24:259-267, 2023. Background: Acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) are illnesses associated with rapid ascent to altitudes over 2,500 m in unacclimatized lowlanders. The aim of this scoping review is to summarize the current knowledge on sex differences in the epidemiology, pathophysiology, symptomatology, and treatment of AMS and HACE, especially in women. Methods and Results: The UIAA Medical Commission convened an international author team to review women's health issues at high altitude and to publish updated recommendations. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including AMS, HACE, and high altitude), with additional publications found by hand search. The primary search focus was for articles assessing lowland women sojourning at high altitude. Results: The literature search yielded 7,165 articles, 37 of which were ultimately included. The majority of publications included did not find women at increased risk for AMS or HACE. There was extremely limited sex-specific data on risk factors or treatment. Conclusions: There is a limited amount of data on female-specific findings regarding AMS and HACE, with most publications addressing only prevalence or incidence with regard to sex. As such, general prevention and treatment strategies for AMS and HACE should be used regardless of sex.

Frostbite and Mortality in Mountaineering Women: A Scoping Review-UIAA Medical Commission Recommendations.

Kriemler, Susi, Kaste Mateikaite-Pipiriene, Alison Rosier, Linda E. Keyes, Peter Paal, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, Lenka Horakova, and Dominique Jean; for the UIAA MedCom Writing Group on Women's Health in the Mountains. Frostbite and mortality in mountaineering women: a scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 24:247-258, 2023. Background: The harsh environment of high altitudes (HA) poses many serious health risks for mountaineers, including cold injuries and death. The aim of this work was to review whether female mountaineers are at special risk for frostbite or death at HA compared with their male counterparts. Methods: The UIAA Medical Commission convened an international author team to review women's health issues at HA and to publish updated recommendations. Pertinent literature from PubMed and Cochrane was identified with additional publications found by hand search. The primary search focus was for articles assessing cold injuries and death in women mountaineers at HA. Results: We reviewed the literature and identified 20 relevant studies: 2 studies on frostbite at HA, plus 7 studies and 1 report for death at HA. An additional 10 studies about frostbite at low altitude were included. We found that female mountaineers at HA were at lower risk of death than their male counterparts, but sex differences in frostbite were inconclusive. Conclusions: The frequency of cold injuries and mortality in female mountaineers is not yet well studied, and the studies that have been published tend to lack precise exposure data. More studies and registries with sex-differentiated data are needed.

Active ascent accelerates the time course but not the overall incidence and severity of acute mountain sickness at 3,600 m.

Acute mountain sickness (AMS) typically peaks following the first night at high altitude (HA) and resolves over the next 2-3 days, but the impact of active ascent on AMS is debated. To determine the impact of ascent conditions on AMS, 78 healthy Soldiers (means ± SD; age = 26 ± 5 yr) were tested at baseline residence, transported to Taos, NM (2,845 m), hiked (n = 39) or were driven (n = 39) to HA (3,600 m), and stayed for 4 days. AMS-cerebral (AMS-C) factor score was assessed at HA twice on day 1 (HA1), five times on days 2 and 3 (HA2 and HA3), and once on day 4 (HA4). If AMS-C was ≥0.7 at any assessment, individuals were AMS susceptible (AMS+; n = 33); others were nonsusceptible (AMS-; n = 45). Daily peak AMS-C scores were analyzed. Ascent conditions (active vs. passive) did not impact the overall incidence and severity of AMS at HA1-HA4. The AMS+ group, however, demonstrated a higher (P < 0.05) AMS incidence in the active vs. passive ascent cohort on HA1 (93% vs. 56%), similar incidence on HA2 (60% vs. 78%), lower incidence (P < 0.05) on HA3 (33% vs. 67%), and similar incidence on HA4 (13% vs. 28%). The AMS+ group also demonstrated a higher (P < 0.05) AMS severity in the active vs. passive ascent cohort on HA1 (1.35 ± 0.97 vs. 0.90 ± 0.70), similar score on HA2 (1.00 ± 0.97 vs. 1.34 ± 0.70), and lower (P < 0.05) score on HA3 (0.56 ± 0.55 vs. 1.02 ± 0.75) and HA4 (0.32 ± 0.41 vs. 0.60 ± 0.72). Active compared with passive ascent accelerated the time course of AMS with more individuals sick on HA1 and less individuals sick on HA3 and HA4.NEW & NOTEWORTHY This research demonstrated that active ascent accelerated the time course but not overall incidence and severity of acute mountain sickness (AMS) following rapid ascent to 3,600 m in unacclimatized lowlanders. Active ascenders became sicker faster and recovered quicker than passive ascenders, which may be due to differences in body fluid regulation. Findings from this well-controlled large sample-size study suggest that previously reported discrepancies in the literature regarding the impact of exercise on AMS may be related to differences in the timing of AMS measurements between studies.

Acute mountain sickness and sleep disturbances differentially influence cognition and mood during rapid ascent to 3000 and 4050 m.

The impact of acute mountain sickness (AMS) and sleep disturbances on mood and cognition at two altitudes relevant to the working and tourist population is unknown. Twenty unacclimatized lowlanders were exposed to either 3000 m (n = 10; 526 mmHg) or 4050 m (n = 10; 460 mmHg) for 20 h in a hypobaric chamber. AMS prevalence and severity was assessed using the Environmental Symptoms Questionnaire (ESQ) and an AMS-C score ≥ 0.7 indicated sickness. While sleeping for one night both at sea level (SL) and high altitude (HA), a wrist motion detector was used to measure awakenings (Awak, events/h) and sleep efficiency (Eff, %). If Eff was ≥85%, individuals were considered a good sleeper (Sleep+). Mood and cognition were assessed using the Automated Neuropsychological Assessment Metric and Mood Scale (ANAM-MS). The ESQ and ANAM-MS were administered in the morning both at SL and after 20 h at HA. AMS severity (mean ± SE; 1.82 ± 0.27 vs. 0.20 ± 0.27), AMS prevalence (90% vs. 10%), depression (0.63 ± 0.23 vs. 0.00 ± 0.24) Awak (15.6 ± 1.6 vs. 10.1 ± 1.6 events/h), and DeSHr (38.5 ± 6.3 vs. 13.3 ± 6.3 events/h) were greater (p < 0.05) and Eff was lower (69.9 ± 5.3% vs. 87.0 ± 5.3%) at 4050 m compared to 3000 m, respectively. AMS presence did not impact cognition but fatigue (2.17 ± 0.37 vs. 0.58 ± 0.39), anger (0.65 ± 0.25 vs. 0.02 ± 0.26), depression (0.63 ± 0.23 vs. 0.00 ± 0.24) and sleepiness (4.8 ± 0.4 vs. 2.7 ± 0.5) were greater (p < 0.05) in the AMS+ group. The Sleep- group, compared to the Sleep+ group, had lower (p < 0.05) working memory scores (50 ± 7 vs. 78 ± 9) assessed by the Sternberg 6-letter memory task, and lower reaction time fatigue scores (157 ± 17 vs. 221 ± 22), assessed by the repeated reaction time test. Overall, AMS, depression, DeSHr, and Awak were increased (p < 0.05) at 4050 m compared to 3000 m. In addition, AMS presence impacted mood while poor sleep impacted cognition which may deteriorate teamwork and/or increase errors in judgement at HA.

Gait instability and estimated core temperature predict exertional heat stroke.

OBJECTIVE: Exertional heat stroke (EHS), characterised by a high core body temperature (Tcr) and central nervous system (CNS) dysfunction, is a concern for athletes, workers and military personnel who must train and perform in hot environments. The objective of this study was to determine whether algorithms that estimate Tcr from heart rate and gait instability from a trunk-worn sensor system can forward predict EHS onset. METHODS: Heart rate and three-axis accelerometry data were collected from chest-worn sensors from 1806 US military personnel participating in timed 4/5-mile runs, and loaded marches of 7 and 12 miles; in total, 3422 high EHS-risk training datasets were available for analysis. Six soldiers were diagnosed with heat stroke and all had rectal temperatures of >41°C when first measured and were exhibiting CNS dysfunction. Estimated core temperature (ECTemp) was computed from sequential measures of heart rate. Gait instability was computed from three-axis accelerometry using features of pattern dispersion and autocorrelation. RESULTS: The six soldiers who experienced heat stroke were among the hottest compared with the other soldiers in the respective training events with ECTemps ranging from 39.2°C to 40.8°C. Combining ECTemp and gait instability measures successfully identified all six EHS casualties at least 3.5 min in advance of collapse while falsely identifying 6.1% (209 total false positives) examples where exertional heat illness symptoms were neither observed nor reported. No false-negative cases were noted. CONCLUSION: The combination of two algorithms that estimate Tcr and ataxic gate appears promising for real-time alerting of impending EHS.

Verification of Maximal Oxygen Uptake in Active Military Personnel During Treadmill Running.

ABSTRACT: Figueiredo, PS, Looney, DP, Pryor, JL, Doughty, EM, McClung, HL, Vangala, SV, Santee, WR, Beidleman, BA, and Potter, AW. Verification of maximal oxygen uptake in active military personnel during treadmill running. J Strength Cond Res 36(4): 1053-1058, 2022-It is unclear whether verification tests are required to confirm "true" maximal oxygen uptake (V̇o2max) in modern warfighter populations. Our study investigated the prevalence of V̇o2max attainment in U.S. Army soldiers performing a traditional incremental running test. In addition, we examined the utility of supramaximal verification testing as well as repeated trials for familiarization for accurate V̇o2max assessment. Sixteen U.S. Army soldiers (1 woman, 15 men; age, 21 ± 2 years; height, 1.73 ± 0.06 m; body mass, 71.6 ± 10.1 kg) completed 2 laboratory visits, each with an incremental running test (modified Astrand protocol) and a verification test (110% maximal incremental test speed) on a motorized treadmill. We evaluated V̇o2max attainment during incremental testing by testing for the definitive V̇O2 plateau using a linear least-squares regression approach. Peak oxygen uptake (V̇o2peak) was considered statistically equivalent between tests if the 90% confidence interval around the mean difference was within ±2.1 ml·kg-1·min-1. Oxygen uptake plateaus were identified in 14 of 16 volunteers for visit 1 (87.5%) and all 16 volunteers for visit 2 (100%). Peak oxygen uptake was not statistically equivalent, apparent from the mean difference in V̇o2peak measures between the incremental test and verification test on visit 1 (2.3 ml·kg-1·min-1, [1.3-3.2]) or visit 2 (1.1 ml·kg-1·min-1 [0.2-2.1]). Interestingly, V̇o2peak was equivalent, apparent from the mean difference in V̇o2peak measures between visits for the incremental tests (0.0 ml·kg-1·min-1 [-0.8 to 0.9]) but not the verification tests (-1.2 ml·kg-1·min-1 [-2.2 to -0.2]). Modern U.S. Army soldiers can attain V̇o2max by performing a modified Astrand treadmill running test. Additional familiarization and verification tests for confirming V̇o2max in healthy active military personnel may be unnecessary.

Impact of 2 days of staging at 2500-4300 m on sleep quality and quantity following subsequent exposure to 4300 m.

The impact of 2 days of staging at 2500-4300 m on sleep quality and quantity following subsequent exposure to 4300 m was determined. Forty-eight unacclimatized men and women were randomly assigned to stage for 2 days at one of four altitudes (2500, 3000, 3500, or 4300 m) prior to assessment on the summit of Pikes Peak (4300 m) for 2 days. Volunteers slept for one night at sea level (SL), two nights at respective staging altitudes, and two nights at Pikes Peak. Each wore a pulse oximeter to measure sleep arterial oxygen saturation (sSpO2 , %) and number of desaturations (DeSHr, events/hr) and a wrist motion detector to estimate sleep awakenings (Awak, awakes/hr) and sleep efficiency (Eff, %). Acute mountain sickness (AMS) was assessed using the Environmental Symptoms Questionnaire and daytime SpO2 was assessed after AMS measurements. The mean of all variables for both staging days (STG) and Pikes Peak days (PP) was calculated. The sSpO2 and daytime SpO2 decreased (p < 0.05) from SL during STG in all groups in a dose-dependent manner. During STG, DeSHr were higher (p < 0.05), Eff was lower (p < 0.05), and AMS symptoms were higher (p < 0.05) in the 3500 and 4300 m groups compared to the 2500 and 3000 m groups while Awak did not differ (p > 0.05) between groups. At PP, the sSpO2 , DeSHr, Awak, and Eff were similar among all groups but the 2500 m group had greater AMS symptoms (p < 0.05) than the other groups. Two days of staging at 2500-4300 m induced a similar degree of sleep acclimatization during subsequent ascent to 4300 m but the 2500 m group was not protected against AMS at 4300 m.

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.

Variability in human plasma volume responses during high-altitude sojourn.

When sea-level (SL) residents rapidly ascend to high altitude (HA), plasma volume (PV) decreases. A quantitative model for predicting individual %∆PV over the first 7 days at HA has recently been developed from the measurements of %∆PV in 393 HA sojourners. We compared the measured %∆PV with the %∆PV predicted by the model in 17 SL natives living 21 days at HA (4300 m). Fasting hematocrit (Hct), hemoglobin (Hb) and total circulating protein (TCP) concentrations at SL and on days 2, 7, 13, and 19 at HA were used to calculate %∆TCP and %∆PV. Mean [95%CI] measured %∆PV on HA2, 7, 13 and 19 was -2.5 [-8.2, 3.1], -11.0 [-16.6, -5.5], -11.7 [-15.9, -7.4], and -16.8 [-22.2, -11.3], respectively. %∆PV and %∆TCP were positively correlated (P < 0.001) at HA2, 7, 13, and 19 (r2  = 0.77, 0.88, 0.78, 0.89, respectively). The model overpredicted mean [95% CI] decrease in %∆PV on HA2 (-12.5 [-13.9, -11.1]) and HA7 (-21.5 [-23.9, -19.1]), accurately predicted the mean decrease on HA13 (-14.3, [-20.0, -8.7]), and predicted a mean increase in %∆PV on HA19 (12.4 [-5.0, 29.8]). On HA2, 7, 13, and 19 only 2, 2, 6, and 1, respectively, of 17 individual measures of %∆PV were within 95% CI for predicted %∆PV. These observations indicate that PV responses to HA are largely oncotically mediated, vary considerably among individuals, and available quantitative models require refinement to predict %∆PV exhibited by individual sojourners.

Two-Day Residence at 2500 m to 4300 m Does Not Affect Subsequent Exercise Performance at 4300 m.

PURPOSE: To determine the efficacy residing for 2 d at various altitudes while sedentary (S) or active (A; ~90 min hiking 2 d) on exercise performance at 4300 m. METHODS: Sea-level (SL) resident men (n = 45) and women (n = 21) (mean ± SD; 23 ± 5 yr; 173 ± 9 cm; 73 ± 12 kg; V˙O2peak = 49 ± 7 mL·kg·min) were randomly assigned to a residence group and, S or A within each group: 2500 m (n = 11S, 8A), 3000 m (n = 6S, 12A), 3500 m (n = 6S, 8A), or 4300 m (n = 7S, 8A). Exercise assessments occurred at SL and 4300 m after 2-d residence and consisted of 20 min of steady-state (SS) treadmill walking (45% ± 3% SL V˙O2peak) and a 5-mile, self-paced running time trial (TT). Arterial oxygen saturation (SpO2) and HR were recorded throughout exercise. Resting SpO2 was recorded at SL, at 4 and 46 h of residence, and at 4300 m before exercise assessment. To determine if 2-d altitude residence improved 4300 m TT performance, results were compared with estimated performances using a validated prediction model. RESULTS: For all groups, resting SpO2 was reduced (P < 0.01) after 4 h of residence relative to SL inversely to the elevation and did not improve after 46 h. Resting SpO2 (~83%) did not differ among groups at 4300 m. Although SL and 4300 m SS exercise SpO2 (97% ± 2% to 74% ± 4%), HR (123 ± 10 bpm to 140 ± 12 bpm) and TT duration (51 ± 9 to 73 ± 16 min) were different (P < 0.01), responses at 4300 m were similar among all groups, as was actual and predicted 4300 m TT performances (74 ± 12 min). CONCLUSIONS: Residing for 2 d at 2500 to 4300 m, with or without daily activity, did not improve resting SpO2, SS exercise responses, or TT performance at 4300 m.

Acute Mountain Sickness is Reduced Following 2 Days of Staging During Subsequent Ascent to 4300 m.

OBJECTIVE: To determine whether 2 days of staging at 2500-3500 m, combined with either high or low physical activity, reduces acute mountain sickness (AMS) during subsequent ascent to 4300 m. METHODS: Three independent groups of unacclimatized men and women were staged for 2 days at either 2500 m (n = 18), 3000 m (n = 16), or 3500 m (n = 15) before ascending and living for 2 days at 4300 m and compared with a control group that directly ascended to 4300 m (n = 12). All individuals departed to the staging altitudes or 4300 m after spending one night at 2000 m during which they breathed supplemental oxygen to simulate sea level conditions. Half in each group participated in ∼3 hours of daily physical activity while half were sedentary. Women accounted for ∼25% of each group. AMS incidence was assessed using the Environmental Symptoms Questionnaire. AMS was classified as mild (≥0.7 and <1.5), moderate (≥1.5 and <2.6), and severe (≥2.6). RESULTS: While staging, the incidence of AMS was lower (p < 0.001) in the 2500 m (0%), 3000 m (13%), and 3500 m (40%) staged groups than the direct ascent control group (83%). After ascent to 4300 m, the incidence of AMS was lower in the 3000 m (43%) and 3500 m (40%) groups than the 2500 m group (67%) and direct ascent control (83%). Neither activity level nor sex influenced the incidence of AMS during further ascent to 4300 m. CONCLUSIONS: Two days of staging at either 3000 or 3500 m, with or without physical activity, reduced AMS during subsequent ascent to 4300 m but staging at 3000 m may be recommended because of less incidence of AMS.

Is normobaric hypoxia an effective treatment for sustaining previously acquired altitude acclimatization?

This study examined whether normobaric hypoxia (NH) treatment is more efficacious for sustaining high-altitude (HA) acclimatization-induced improvements in ventilatory and hematologic responses, acute mountain sickness (AMS), and cognitive function during reintroduction to altitude (RA) than no treatment at all. Seventeen sea-level (SL) residents (age = 23 ± 6 yr; means ± SE) completed in the following order: 1) 4 days of SL testing; 2) 12 days of HA acclimatization at 4,300 m; 3) 12 days at SL post-HA acclimatization (Post) where each received either NH (n = 9, [Formula: see text] = 0.122) or Sham (n = 8; [Formula: see text] = 0.207) treatment; and 4) 24-h reintroduction to 4,300-m altitude (RA) in a hypobaric chamber (460 Torr). End-tidal carbon dioxide pressure ([Formula: see text]), hematocrit (Hct), and AMS cerebral factor score were assessed at SL, on HA2 and HA11, and after 20 h of RA. Cognitive function was assessed using the SynWin multitask performance test at SL, on HA1 and HA11, and after 4 h of RA. There was no difference between NH and Sham treatment, so data were combined. [Formula: see text] (mmHg) decreased from SL (37.2 ± 0.5) to HA2 (32.2 ± 0.6), decreased further by HA11 (27.1 ± 0.4), and then increased from HA11 during RA (29.3 ± 0.6). Hct (%) increased from SL (42.3 ± 1.1) to HA2 (45.9 ± 1.0), increased again from HA2 to HA11 (48.5 ± 0.8), and then decreased from HA11 during RA (46.4 ± 1.2). AMS prevalence (%) increased from SL (0 ± 0) to HA2 (76 ± 11) and then decreased at HA11 (0 ± 0) and remained depressed during RA (17 ± 10). SynWin scores decreased from SL (1,615 ± 62) to HA1 (1,306 ± 94), improved from HA1 to HA11 (1,770 ± 82), and remained increased during RA (1,707 ± 75). These results demonstrate that HA acclimatization-induced improvements in ventilatory and hematologic responses, AMS, and cognitive function are partially retained during RA after 12 days at SL whether or not NH treatment is utilized.NEW & NOTEWORTHY This study demonstrates that normobaric hypoxia treatment over a 12-day period at sea level was not more effective for sustaining high-altitude (HA) acclimatization during reintroduction to HA than no treatment at all. The noteworthy aspect is that athletes, mountaineers, and military personnel do not have to go to extraordinary means to retain HA acclimatization to an easily accessible and relevant altitude if reexposure occurs within a 2-wk time period.

Quantitative model of hematologic and plasma volume responses after ascent and acclimation to moderate to high altitudes.

Despite decades of research, the magnitude and time course of hematologic and plasma volume (PV) changes following rapid ascent and acclimation to various altitudes are not precisely described. To develop a quantitative model, we utilized a comprehensive database and general linear mixed models to analyze 1,055 hemoglobin ([Hb]) and hematocrit (Hct) measurements collected at sea level and repeated time points at various altitudes in 393 unacclimatized men (n = 270) and women (n = 123) who spent between 2 h and 7 days at 2,500-4,500 m under well-controlled and standardized experimental conditions. The PV change (ΔPV) was calculated from [Hb] and Hct measurements during a time period when erythrocyte volume is stable. The results are 1) ΔPV decreases rapidly (~6%) after the 1st day at 2,500 m and [Hb] and Hct values increase by 0.5 g/dl and 1.5 points, respectively; 2) ΔPV decreases an additional 1%, and [Hb] and Hct increase an additional 0.1 g/dl and 0.2 points every 500-m increase in elevation above 2,500 m after the 1st day; 3) ΔPV continues to decrease over time at altitude, but the magnitude of this decrease and subsequent increase in [Hb] and Hct levels is dependent on elevation and sex; and 4) individuals with high initial levels of [Hb] and Hct and older individuals hemoconcentrate less at higher elevations. This study provides the first quantitative delineation of ΔPV and hematological responses during the first week of exposure over a wide range of altitudes and demonstrates that absolute altitude and time at altitude, as well as initial hematologic status, sex, and age impact the response.

Quantitative Model of Sustained Physical Task Duration at Varying Altitudes.

PURPOSE: The objective of this study is to develop a quantitative model that can be used before ascent to altitude (ALT) to predict how much longer a sustained physical task would take for unacclimatized individuals in the early hours of exposure. METHODS: Using multiple linear regression, we analyzed time-trial (TT) performance on 95 unacclimatized men (n = 83) and women (n = 12) at sea level (SL) and at an ALT ranging from 2500 to 4300 m. The TT was initiated within 4 h of ascent to ALT. The independent variables known before ascent were as follows: ALT, age, height, weight, sex, SL peak oxygen uptake, SL task duration time, and body mass index (BMI) classification (normal weight vs overweight). The dependent variable was the percent increase in TT duration from SL to ALT. RESULTS: The most significant factor in the model was ALT (P = 0.0001), followed by BMI classification (P = 0.0009) and the interaction between BMI classification and ALT (P = 0.003). The model is as follows: percent increase in TT duration = [100 + e(-1.517+1.323 (ALT)+3.124 (BMI class)-0.769 (ALT) (BMI class)]. The percent increase in TT duration in overweight individuals was 129% greater than for normal-weight individuals at 3000 m. However, as ALT increased beyond 3000 m, the disparity between groups decreased until 4050 m where the percent increase in TT duration became greater for normal-weight individuals. CONCLUSIONS: This model provides the first quantitative estimates of the percent increase in sustained physical task duration during initial exposure to a wide range of elevations. Because only two easily obtainable factors are required as inputs for the model (ALT and BMI classification), this model can be used by many unacclimatized individuals to better plan their activities at ALT.

Cycling performance decrement is greater in hypobaric versus normobaric hypoxia.

BACKGROUND: The purpose of this study was to determine whether cycling time trial (TT) performance differs between hypobaric hypoxia (HH) and normobaric hypoxia (NH) at the same ambient PO2 (93 mmHg, 4,300-m altitude equivalent). METHODS: Two groups of healthy fit men were matched on physical performance and demographic characteristics and completed a 720-kJ time trial on a cycle ergometer at sea level (SL) and following approximately 2 h of resting exposure to either HH (n = 6, 20 ± 2 years, 75.2 ± 11.8 kg, mean ± SD) or NH (n = 6, 21 ± 3 years, 77.4 ± 8.8 kg). Volunteers were free to manually increase or decrease the work rate on the cycle ergometer. Heart rate (HR), arterial oxygen saturation (SaO2), and rating of perceived exertion (RPE) were collected every 5 min during the TT, and the mean was calculated. RESULTS: Both groups exhibited similar TT performance (min) at SL (73.9 ± 7.6 vs. 73.2 ± 8.2), but TT performance was longer (P < 0.05) in HH (121.0 ± 12.1) compared to NH (99.5 ± 18.1). The percent decrement in TT performance from SL to HH (65.1 ± 23.6%) was greater (P < 0.05) than that from SL to NH (35.5 ± 13.7%). The mean exercise SaO2, HR, and RPE during the TT were not different in HH compared to NH. CONCLUSION: Cycling time trial performance is impaired to a greater degree in HH versus NH at the same ambient PO2 equivalent to 4,300 m despite similar cardiorespiratory responses.

Evaluating the molecular basis for acute mountain sickness: hypoxia response gene expression patterns in warfighters and murine populations.

Acute mountain sickness (AMS) is an illness that affects many individuals at altitudes above 2,400 m (8,000 ft) resulting in decreased performance. Models that provide quantitative estimates of AMS risk are expanding, but predictive genetic models for AMS susceptibility are still under investigation. Thirty-four male U.S. Army Soldier volunteers were exposed to baseline, 3,000 m, 3,500 m, or 4,500 m altitude conditions in a hypobaric chamber and evaluated for onset of AMS symptoms. In addition, mice were evaluated at extreme hypoxia conditions equivalent to 7,600 m. Real-time polymerase chain reaction hypoxia response array was used to identify 15 genes that were activated in Soldiers and 46 genes that were activated in mice. We identified angiopoietin-like 4 (ANGPTL4) as a gene that is significantly activated in response to hypoxia (5.8-fold upregulated at 4,500 m in humans). The role of ANGPTL4 in high-altitude response has not been explored. Pretreatment of mice with fenofibrate, an ANGPTL4-activating pharmaceutical, had a considerable effect on overall hypoxia response gene expression and resulted in significantly decreased cerebral edema following exposure to hypoxia. Activation of ANGPTL4 may protect against cerebral edema by inhibiting vascular endothelial growth factor and therefore serve as a potential target for AMS prevention.