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Committeri Giorgia, Danilo Bondi, Carlo Sestieri, Ginevra Di Matteo, Claudia Piervincenzi, Christian Doria, Roberto Ruffini, Antonello Baldassarre, Tiziana Pietrangelo, Rosamaria Sepe, Riccardo Navarra, Piero Chiacchiaretta, Antonio Ferretti, and Vittore Verratti. Neuropsychological and neuroimaging correlates of high-altitude hypoxia trekking during the "Gokyo Khumbu/Ama Dablam" expedition. High Alt Med Biol . 23:57-68, 2022. Background: Altitude hypoxia exposure may produce cognitive detrimental adaptations and damage to the brain. We aimed at investigating the effects of trekking and hypoxia on neuropsychological and neuroimaging measures. Methods: We recruited two balanced groups of healthy adults, trekkers ( n  = 12, 6 F and 6 M, trekking in altitude hypoxia) and controls (gender- and age-matched), who were tested before (baseline), during (5,000 m, after 9 days of trekking), and after the expedition for state anxiety, depression, verbal fluency, verbal short-term memory, and working memory. Personality and trait anxiety were also assessed at a baseline level. Neuroimaging measures of cerebral perfusion (arterial spin labeling), white-matter microstructural integrity (diffusion tensor imaging), and resting-state functional connectivity (functional magnetic resonance imaging) were assessed before and after the expedition in the group of trekkers. Results: At baseline, the trekkers showed lower trait anxiety ( p  = 0.003) and conscientiousness ( p  = 0.03) than the control group. State anxiety was lower in the trekkers throughout the study ( p  < 0.001), and state anxiety and depression decreased at the end of the study in both groups ( p  = 0.043 and p  = 0.007, respectively). Verbal fluency increased at the end of the study in both groups ( p  < 0.001), whereas verbal short-term memory and working memory performance did not change. No significant differences between before and after the expedition were found for neuroimaging measures. Conclusions: We argue that the observed differences in the neuropsychological measures mainly reflect aspecific familiarity and learning effects due to the repeated execution of the same questionnaires and task. The present results thus suggest that detrimental effects on neuropsychological and neuroimaging measures do not necessarily occur as a consequence of short-term exposure to altitude hypoxia up to 5,000 m, especially in the absence of altitude sickness.

Altitude hypoxia induces changes in iron homeostasis with serum ferritin (sFER) response being recently linked to erythropoiesis. The main aim of this study was to investigate sFER and Vitamin D (Vit D) response to hypobaric hypoxia, taking into account factors including nutrition and ethnic origin. As part of a "Kanchenjunga Exploration & Physiology" project, 6 Italian trekkers and 6 Nepalese porters took part in a 19-days long altitude trek in the Himalayas self-recording daily food consumption. Blood samples were collected and analyzed before and after the trek for sFER and Vit D. A web-based system calculated the dietary intake, generating reports that were used for later statistical analyses. sFER decreased after the trek (on average by 26% p  = 0.013, partial η 2  = 0.479) in both groups, whereas Vit D did not change in both groups. Nepalese tended to have lower sFER, but this difference was reduced when corrected for the dietary intake. Mean Cell Volume (MCV) and Hematocrit (HCT), in respect to baseline, remained higher 10 days after the trek (respectively, 87.37-88.85 fL with p  = 0.044, and 43.05-44.63% with p  = 0.065) in Italian trekkers. The observed reduction of sFER levels was related to altitude per se as inflammation or anemia were medically excluded. sFER, therefore, may act as a primary factor in the examination of hypobaric hypoxia in field studies. The results of this study open a new door into the mechanisms of iron homeostasis in specific tissues related to hypoxia adaptations, taking into account dietary intake and ethnic origin.

High-altitude exposure leads to many physiological challenges, such as weight loss and dehydration. However, little attention has been posed to the role of nutrition and ethnic differences. Aiming to fulfill this gap, five Italian trekkers and seven Nepalese porters, all males, recorded their diet in diaries during a Himalayan expedition (19 days), and the average daily intake of micro and macro-nutrients were calculated. Bioimpedance analysis was performed five times during the trek; muscle ultrasound was performed before and after the expedition, only for the Italians. The Nepalese group consumed a lot of rice and only Italians consumed cheese. Water intake was slightly over 3000 g/d for both groups. Nepalese diet had a higher density of dietary fibre and lower density of riboflavin, vitamins A, K, and B12. Intake of calcium was lower than recommended levels. Body mass index, waist circumference, fat-free mass, and total body water decreased in both groups, whereas resistance (Rz) increased. Italians reactance (Xc) increased at day 9, whereas that of Nepalese occurred at days 5, 9, and 16. The cross-sectional area of the Vastus lateralis was reduced after the expedition. Specific nutritional and food-related risk factors guidance is needed for diverse expedition groups. Loss of muscle mass and balance of fluids both deserve a particular focus as concerns altitude expeditions.

Altitude exposure affects hormonal homeostasis, but the adaptation of different populations is still not finely defined. This study aims to compare the mid-term effects of combining physical activity and altitude hypoxia on hormonal profiles in foreign trekkers coming from Italy versus indigenous Nepalese porters during a Himalayan trek. Participants (6 Italians and 6 Nepalese) completed a 300 km distance in 19 days of an accumulated altitude difference of 16,000 m, with an average daily walk of 6 h. The effect of high altitude on hormonal pathways was assessed by collecting blood samples the day before the expedition and the day after its completion. Foreign trekkers had an additional follow-up sample collected after 10 days. The findings revealed a different adaptation of thyroidal and gonadal axes to mid-term strenuous physical activity combined with high-altitude hypobaric hypoxia. The thyroid function shifted to the protective mechanism of low free triiodothyronine (FT3), whereas the gonadal axis was suppressed. The Italian trekkers and Nepalese porters had lower total testosterone and 17-β-estradiol levels after the expedition. At the follow-up, the Italians had increased testosterone values. Prolactin secretion decreased in the Italians but increased in the Nepalese. We conclude that exposure to high-altitude affects the hormonal axes. The effect seems notably pronounced for the hypothalamus-pituitary gonadal axis, suppressed after high-altitude exposure., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The purpose of this study was to analyze the physiological features of peripheral blood mononuclear cells (PBMCs) isolated from healthy female trekkers before and after physical activity carried out under both normoxia (low altitude, < 2000 m a.s.l.) and hypobaric hypoxia (high altitude, > 3700 m a.s.l.). The experimental design was to differentiate effects induced by exercise and those related to external environmental conditions. PBMCs were isolated from seven female subjects before and after each training period. The PBMCs were phenotypically and functionally characterized using fluorimetric and densitometric analyses, to determine cellular activation, and their intracellular Ca(2+) levels and oxidative status. After a period of normoxic physical exercise, the PBMCs showed an increase in fully activated T lymphocytes (CD3(+) CD69(+) ) and a reduction in intracellular Ca(2+) levels. On the other hand, with physical exercise performed under hypobaric hypoxia, there was a reduction in T lymphocytes and an increase in nonactivated B lymphocytes, accompanied by a reduction in O2 (-) levels in the mitochondria. These outcomes reveal that in women, low- to moderate-intensity aerobic trekking induces CD69 T cell activation and promotes anti-stress effects on the high-altitude-induced impairment of the immune responses and the oxidative balance., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The study investigated the effect of prolonged hypoxia on central [i.e., cardiovascular oxygen delivery (Q(a)O(2))] and peripheral (i.e., O(2) utilization) determinants of oxidative metabolism response during exercise in humans. To this aim, seven male mountaineers were examined before and immediately after the Himalayan Expedition Interamnia 8000-Manaslu 2008, lasting 43 days, among which, 23 days were above 5,000 m. The subjects showed a decrease in body weight (P < 0.05) and of power output during a Wingate Anaerobic test (P < 0.05) and an increase of thigh cross-sectional area (P < 0.05). Absolute maximal O(2) uptake (VO(2max)) did not change. The mean response time of VO(2) kinetics at the onset of step submaximal cycling exercise was reduced significantly from 53.8 s ± 10.9 to 39.8 s ± 10.9 (P < 0.05), whereas that of Q(a)O(2) was not. Analysis of single fibers dissected from vastus lateralis biopsies revealed that the expression of slow isoforms of both heavy and light myosin subunits increased, whereas that of fast isoforms decreased. Unloaded shortening velocity of fibers was decreased significantly. In summary, independent findings converge in indicating that adaptation to chronic hypoxia brings about a fast-to-slow transition of muscle fibers, resulting in a faster activation of the mitochondrial oxidative metabolism. These results indicate that a prolonged and active sojourn in hypoxia may induce muscular ultrastructural and functional changes similar to those observed after aerobic training.

Objective: To explore the effect of physical exercise at high altitudes (HA) on male reproductive system., Design: Prospective study., Setting: Andrology Clinic, University of L'Aquila, Italy., Patient(s): Seven male mountaineers involved in an expedition at 5,900 m., Intervention(s): Semen analysis, sperm DNA fragmentation with flow cytometry, and reproductive hormone levels., Main Outcome Measure(s): Hormone levels were evaluated at sea level (SL) at baseline (SL-pre), after 22 days of exercise at HA (intermediate), and after 10 days upon reaching SL (SL-post). Sperm parameters, percentage of sperm with fragmented DNA, and body composition measures were evaluated at SL-pre and at SL-post., Result(s): A reduction of sperm concentration, of body mass index (BMI), of waist circumference, and of percentage of body fat was observed at SL-post compared with SL-pre values. Increased levels of FSH and PRL were observed at the intermediate point, and normalized at SL-post, whereas T was higher at SL-post compared with SL-pre levels., Conclusion(s): Physical exercise at HA is associated with a testicular dysfunction leading to a reduced sperm concentration probably through an altered spermiation. The improved body composition after physical exercise might explain the higher T levels observed after the expedition., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)