Advances in the Prevention and Treatment of High-Altitude Illnesses
DOI:
https://doi.org/10.12775/JEHS.2026.91.70950Keywords
Altitude sickness, acclimatization, oxygen saturation, hypoxia, prediction algorithmsAbstract
Introduction and purpose
High-altitude environments (>1500 m) expose climbers to reduced atmospheric pressure and hypoxia. These conditions increase the risk of acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. This review aims to summarize current knowledge of high-altitude illnesses (HAI), their prevention and treatment, with particular emphasis on recent advances in this field.
A brief description of the state of knowledge
Prophylaxis of HAI is based on proper acclimatization and a suitable ascent rate. Acetazolamide is among the most commonly used agents for pharmacologic prophylaxis. Treatment in severe cases requires prompt descent, oxygen therapy, dexamethasone, or portable hyperbaric chambers. There are numerous novel strategies used for reducing the risk of HAI. Emerging evidence suggests that probiotics may facilitate acclimatization. Pre-acclimatization and hypoxic training at sea level enable preparation for high-altitude exposure. Wearable sensors and closed-loop systems may provide more precise risk assessment; however, their effectiveness in mountainous conditions remains to be improved. Advanced prediction models, in turn, additionally improve the identification of people from risk groups and facilitate personalized prophylaxis.
Summary (conclusions)
HAI remain an important challenge in hypoxic, mountainous conditions. Apart from the currently well-established methods, novel strategies, such as probiotics, hypoxic training, and advanced monitoring technologies, may facilitate prophylaxis and individual risk assessment, thus improving the security of high-altitude expeditions.
References
1. Government of Nepal, Ministry of Culture, Tourism and Civil Aviation. Nepal Tourism Statistics 2014. Kathmandu: Ministry of Culture, Tourism and Civil Aviation; 2015. p. 48. Available from: https://trade.ntb.gov.np/wp-content/uploads/2016/01/Nepal_Tourism_Statistics_2014_Integrated.pdf [accessed 2026 Apr 11]
2. Government of Nepal, Ministry of Culture, Tourism and Civil Aviation. Nepal Tourism Statistics 2024. Kathmandu: Ministry of Culture, Tourism and Civil Aviation; 2024. p. 45. Available from: https://giwmscdnone.gov.np/media/pdf_upload/Nepal%20tourism%20statistics%202024_gdm4eag.pdf [accessed 2026 Apr 11]
3. Hackett PH, Roach RC. High-altitude medicine. In: Auerbach PS, editor. Wilderness medicine. 3rd ed. St. Louis: Mosby; 1995. p. 1–37.
4. Taylor AT. High-altitude illnesses: physiology, risk factors, prevention, and treatment. Rambam Maimonides Med J. 2011;2(1):e0022. https://doi.org/10.5041/rmmj.10022
5. International Climbing and Mountaineering Federation. Diploma in mountain medicine [Internet]. Available from: https://www.theuiaa.org/mountain-medicine/diploma-in-mountain-medicine/ [accessed 2026 Apr 11]
6. McLaughlin K, Roy S, Falla M, Strapazzon G, Luks AM, Zafren K, et al. Pharmacological Prophylaxis and Supplemental Oxygen for Unacclimatized Rescuers at Very High Altitude: Scoping Review and 2025 Joint Recommendations of the International Commission for Mountain Emergency Medicine and the International Society for Mountain Medicine. High Alt Med Biol. 2026;27(1):60-77. https://doi.org/10.1177/15578682251365931
7. Burtscher J, Swenson ER, Hackett PH, Millet GP, Burtscher M. Flying to high-altitude destinations: Is the risk of acute mountain sickness greater? J Travel Med. 2023;30(4). https://doi.org/10.1093/jtm/taad011
8. Horiuchi M, Endo J, Akatsuka S, Uno T, Jones TE. Prevalence of acute mountain sickness on Mount Fuji: A pilot study. Journal of Travel Medicine. 2016;23(4). https://doi.org/10.1093/jtm/taw024
9. Kosek S, Klonowska J, Walkowski R, Wasiniewska W, Barański M, Kandefer T, et al. High Altitude Diseases: Epidemiology, Pathophysiology, Diagnosis, Prevention and Treatment. Quality in Sport. 2026;49:67455. https://doi.org/10.12775/QS.2026.49.67455
10. Meier D, Collet T-H, Locatelli I, Cornuz J, Kayser B, Simel DL, et al. Does This Patient Have Acute Mountain Sickness?: The Rational Clinical Examination Systematic Review. JAMA. 2017;318(18):1810-9. https://doi.org/10.1001/jama.2017.16192
11. Roach RC, Hackett PH, Oelz O, Bärtsch P, Luks AM, MacInnis MJ, et al. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol. 2018;19(1):4-6. https://doi.org/10.1089/ham.2017.0164
12. Hackett PH, Roach RC. High-altitude illness. N Engl J Med. 2001;345(2):107-14. https://doi.org/10.1056/nejm200107123450206
13. Mazur K, Machaj D, Jastrzębska S, Płaczek A, Mazur D. Prevention and treatment of high altitude pulmonary edema (HAPE). Journal of Education, Health and Sport. 2020;10(2):114-9. https://doi.org/10.12775/JEHS.2020.10.02.015
14. Bärtsch P, Mairbäurl H, Maggiorini M, Swenson ER. Physiological aspects of high-altitude pulmonary edema. Journal of Applied Physiology. 2005;98(3):1101-10. https://doi.org/10.1152/japplphysiol.01167.2004
15. Bärtsch P, Swenson ER. Acute High-Altitude Illnesses. New England Journal of Medicine. 2013;368(24):2294-302. https://doi.org/doi:10.1056/NEJMcp1214870
16. Turner REF, Gatterer H, Falla M, Lawley JS. High-altitude cerebral edema: its own entity or end-stage acute mountain sickness? J Appl Physiol (1985). 2021;131(1):313-25. https://doi.org/10.1152/japplphysiol.00861.2019
17. Mazur K, Machaj D, Jastrzębska S, Płaczek A, Mazur D. Prevention and treatment of high altitude cerebral edema (HACE). Journal of Education, Health and Sport. 2020;10(2):120-5. https://doi.org/10.12775/JEHS.2020.10.02.016
18. Moczydłowski P, Kuczapska K, Gliwa A, Ryglewicz M, Fabian D, Leszczyńska-Knaga E, et al. Acute mountain sickness: pathophysiology and prevention. Quality in Sport. 2025;37:57019. https://doi.org/10.12775/QS.2025.37.57019
19. Sareban M, Schiefer LM, Macholz F, Schäfer L, Zangl Q, Inama F, et al. Endurance Athletes Are at Increased Risk for Early Acute Mountain Sickness at 3450 m. Medicine & Science in Sports & Exercise. 2020;52(5):1109-15. https://doi.org/10.1249/mss.0000000000002232
20. Choroszewicz P, Dobosiewicz AM, Badiuk N. Acetazolamide in prevention of altitude disease. Pedagogy and Psychology of Sport. 2020;6(2):95-103. https://doi.org/10.12775/PPS.2020.06.02.009
21. Luks AM, Beidleman BA, Freer L, Grissom CK, Keyes LE, McIntosh SE, et al. Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update. Wilderness & Environmental Medicine. 2024;35(1_suppl):2S-19S. https://doi.org/10.1016/j.wem.2023.05.013
22. Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. Journal of Applied Physiology. 2007;102(4):1313-22. https://doi.org/10.1152/japplphysiol.01572.2005
23. Burtscher J, Gatterer H, Beidleman BA, Burtscher M. Dexamethasone for prevention of AMS, HACE, and HAPE and for limiting impairment of performance after rapid ascent to high altitude: a narrative review. Mil Med Res. 2025;12(1):48. https://doi.org/10.1186/s40779-025-00634-y
24. Wakeham DJ, Tomlinson AR, Manferdelli G, Howrey MM, Geib AK, Ramanathan M, et al. The Physiological and Altitude Lowering Effects of Different Supplemental Oxygen Flow Rates at Extreme Simulated Altitude: A Pilot Study. High Alt Med Biol. 2025. https://doi.org/10.1177/15578682251396453
25. Simancas‐Racines D, Arevalo‐Rodriguez I, Osorio D, Franco JVA, Xu Y, Hidalgo R. Interventions for treating acute high altitude illness. Cochrane Database of Systematic Reviews. 2018(6). https://doi.org/10.1002/14651858.CD009567.pub2
26. Guo J, Zhao R, Li K, Tan Y, Wang L, Ling H, et al. Altitude adaptation: The unseen work of gut microbiota. hLife. 2025;3(1):5-20. https://doi.org/10.1016/j.hlife.2024.11.004
27. Lombardi F, Augello FR, Palumbo P, Bonfili L, Artone S, Altamura S, et al. Bacterial Lysate from the Multi-Strain Probiotic SLAB51 Triggers Adaptative Responses to Hypoxia in Human Caco-2 Intestinal Epithelial Cells under Normoxic Conditions and Attenuates LPS-Induced Inflammatory Response. International Journal of Molecular Sciences. 2023;24(9):8134. https://doi.org/10.3390/ijms24098134
28. Semenza GL. Oxygen sensing, homeostasis, and disease. N Engl J Med. 2011;365(6):537-47. https://doi.org/10.1056/NEJMra1011165
29. Yu JJ, Moya EA, Cheng H, Kaya K, Ochoa T, Fassardi S, et al. Improved oxygen saturation and acclimatization with bacteriotherapy at high altitude. iScience. 2025;28(4). https://doi.org/10.1016/j.isci.2025.112053
30. Marzola M, Marazzato M, Nutini R, Di Marzio A, Baroli F, Paolucci M, et al. Effects of OXXYSLAB Probiotic Supplementation on Blood Oxygenation and Hypoxic Symptoms in Healthy Individuals: A Controlled Normobaric Hypoxia Trial. High Alt Med Biol. 2026:15578682261415833. https://doi.org/10.1177/15578682261415833
31. Ceccarelli G, Marazzato M, Celani L, Lombardi F, Piccirilli A, Mancone M, et al. Oxygen Sparing Effect of Bacteriotherapy in COVID-19. Nutrients. 2021;13(8):2898. https://doi.org/10.3390/nu13082898
32. Dünnwald T, Kienast R, Niederseer D, Burtscher M. The Use of Pulse Oximetry in the Assessment of Acclimatization to High Altitude. Sensors (Basel). 2021;21(4). https://doi.org/10.3390/s21041263
33. Luks AM, Hackett PH. Medical Conditions and High-Altitude Travel. New England Journal of Medicine. 2022;386(4):364-73. https://doi.org/doi:10.1056/NEJMra2104829
34. Seiler T, Nakas CT, Brill AK, Hefti U, Hilty MP, Perret-Hoigné E, et al. Do cardiopulmonary exercise tests predict summit success and acute mountain sickness? A prospective observational field study at extreme altitude. Br J Sports Med. 2023;57(14):906-13. https://doi.org/10.1136/bjsports-2022-106211
35. Goves JSL, Joyce KE, Broughton S, Greig J, Ashdown K, Bradwell AR, et al. Pulse oximetry for the prediction of acute mountain sickness: A systematic review. Exp Physiol. 2024;109(12):2057-72. https://doi.org/10.1113/ep091875
36. Schiefer LM, Treff G, Treff F, Schmidt P, Schäfer L, Niebauer J, et al. Validity of Peripheral Oxygen Saturation Measurements with the Garmin Fēnix® 5X Plus Wearable Device at 4559 m. Sensors. 2021;21(19):6363. https://doi.org/10.3390/s21196363
37. Hermand E, Coll C, Richalet JP, Lhuissier FJ. Accuracy and Reliability of Pulse O2 Saturation Measured by a Wrist-worn Oximeter. Int J Sports Med. 2021;42(14):1268-73. https://doi.org/10.1055/a-1337-2790
38. Petek BJ, Al-Alusi MA, Moulson N, Grant AJ, Besson C, Guseh JS, et al. Consumer Wearable Health and Fitness Technology in Cardiovascular Medicine: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023;82(3):245-64. https://doi.org/10.1016/j.jacc.2023.04.054
39. Gassmann M, Muckenthaler MU. Adaptation of iron requirement to hypoxic conditions at high altitude. J Appl Physiol (1985). 2015;119(12):1432-40. https://doi.org/10.1152/japplphysiol.00248.2015
40. Goetze O, Schmitt J, Spliethoff K, Theurl I, Weiss G, Swinkels DW, et al. Adaptation of iron transport and metabolism to acute high-altitude hypoxia in mountaineers. Hepatology. 2013;58(6):2153-62. https://doi.org/10.1002/hep.26581
41. Piperno A, Galimberti S, Mariani R, Pelucchi S, Ravasi G, Lombardi C, et al. Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project. Blood. 2011;117(10):2953-9. https://doi.org/10.1182/blood-2010-08-299859
42. Geng Y, Hu Y, Wang H, Zhang F, Ge RL. Reduced iron bioavailability drives acute high‑altitude lung injury through HIF1α activation and mitophagy. Mol Med Rep. 2025;32(2). https://doi.org/10.3892/mmr.2025.13580
43. Patrician A, Dawkins T, Coombs GB, Stacey B, Gasho C, Gibbons T, et al. Global Research Expedition on Altitude-related Chronic Health 2018 Iron Infusion at High Altitude Reduces Hypoxic Pulmonary Vasoconstriction Equally in Both Lowlanders and Healthy Andean Highlanders. Chest. 2022;161(4):1022-35. https://doi.org/10.1016/j.chest.2021.08.075
44. Willie CK, Patrician A, Hoiland RL, Williams AM, Gasho C, Subedi P, et al. Influence of iron manipulation on hypoxic pulmonary vasoconstriction and pulmonary reactivity during ascent and acclimatization to 5050 m. J Physiol. 2021;599(5):1685-708. https://doi.org/10.1113/jp281114
45. Molano Franco D, Nieto Estrada VH, Gonzalez Garay AG, Martí‐Carvajal AJ, Arevalo‐Rodriguez I. Interventions for preventing high altitude illness: Part 3. Miscellaneous and non‐pharmacological interventions. Cochrane Database of Systematic Reviews. 2019(4). https://doi.org/10.1002/14651858.CD013315
46. Talbot NP, Smith TG, Privat C, Nickol AH, Rivera-Ch M, León-Velarde F, et al. Intravenous iron supplementation may protect against acute mountain sickness: a randomized, double-blinded, placebo-controlled trial. High Alt Med Biol. 2011;12(3):265-9. https://doi.org/10.1089/ham.2011.1005
47. Ren X, Zhang Q, Wang H, Man C, Hong H, Chen L, et al. Effect of Intravenous Iron Supplementation on Acute Mountain Sickness: A Preliminary Randomized Controlled Study. Med Sci Monit. 2015;21:2050-7. https://doi.org/10.12659/msm.891182
48. Bradbury KE, Gideon EA, Baranauskas MN, Betts AW, Davis KA, DiMarco KG, et al. Impact of intravenous iron or exogenous erythropoietin on hemoglobin mass, exercise performance, and acute mountain sickness during altitude acclimatization. J Appl Physiol (1985). 2025;139(4):954-63. https://doi.org/10.1152/japplphysiol.00076.2025
49. Salgado RM, Mayer TA, Giersch GEW, Alba BK, Barney DE, Jr., Caldwell AR, et al. Augmenting erythropoiesis using recombinant human erythropoietin at sea level blunts the high altitude induced increase in erythropoiesis. J Physiol. 2026. https://doi.org/10.1113/jp289440
50. Qing K, Tustison NJ, Mugler JP, 3rd, Mata JF, Lin Z, Zhao L, et al. Probing Changes in Lung Physiology in COPD Using CT, Perfusion MRI, and Hyperpolarized Xenon-129 MRI. Acad Radiol. 2019;26(3):326-34. https://doi.org/10.1016/j.acra.2018.05.025
51. Hwang HJ, Lee SM, Seo JB, Lee JS, Kim N, Lee SW, et al. Visual and Quantitative Assessments of Regional Xenon-Ventilation Using Dual-Energy CT in Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: A Comparison with Chronic Obstructive Pulmonary Disease. Korean J Radiol. 2020;21(9):1104-13. https://doi.org/10.3348/kjr.2019.0936
52. Law LS, Lo EA, Gan TJ. Xenon Anesthesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Anesth Analg. 2016;122(3):678-97. https://doi.org/10.1213/ane.0000000000000914
53. Liang M, Ahmad F, Dickinson R. Neuroprotection by the noble gases argon and xenon as treatments for acquired brain injury: a preclinical systematic review and meta-analysis. Br J Anaesth. 2022;129(2):200-18. https://doi.org/10.1016/j.bja.2022.04.016
54. Hilty MP, Hefti U, Bouzat P, Gatterer H, Horakova L, Keyes LE, et al. Xenon Inhalation for Expeditions to High Altitude: A Position Statement from the International Climbing and Mountaineering Federation (Union Internationale des Associations d'Alpinisme, UIAA) Medical Commission. High Alt Med Biol. 2025;26(4):385-7. https://doi.org/10.1089/ham.2025.0018
55. Stoppe C, Ney J, Brenke M, Goetzenich A, Emontzpohl C, Schälte G, et al. Sub-anesthetic Xenon Increases Erythropoietin Levels in Humans: A Randomized Controlled Trial. Sports Med. 2016;46(11):1753-66. https://doi.org/10.1007/s40279-016-0505-1
56. Ma D, Lim T, Xu J, Tang H, Wan Y, Zhao H, et al. Xenon preconditioning protects against renal ischemic-reperfusion injury via HIF-1alpha activation. J Am Soc Nephrol. 2009;20(4):713-20. https://doi.org/10.1681/asn.2008070712
57. Dias KA, Lawley JS, Gatterer H, Howden EJ, Sarma S, Cornwell WK, 3rd, et al. Effect of acute and chronic xenon inhalation on erythropoietin, hematological parameters, and athletic performance. J Appl Physiol (1985). 2019;127(6):1503-10. https://doi.org/10.1152/japplphysiol.00289.2019
58. Lawley JS, Gatterer H, Dias KA, Howden EJ, Sarma S, Cornwell WK, 3rd, et al. Safety, hemodynamic effects, and detection of acute xenon inhalation: rationale for banning xenon from sport. J Appl Physiol (1985). 2019;127(6):1511-8. https://doi.org/10.1152/japplphysiol.00290.2019
59. Shi D, Chen J, Li M, Zhu L, Ji X. Closing the loop: autonomous intelligent control for hypoxia pre-acclimatization and high-altitude health management. Natl Sci Rev. 2025;12(5):nwaf071. https://doi.org/10.1093/nsr/nwaf071
60. Gangwar A, Pooja, Sharma M, Singh K, Patyal A, Bhaumik G, et al. Intermittent normobaric hypoxia facilitates high altitude acclimatization by curtailing hypoxia-induced inflammation and dyslipidemia. Pflügers Archiv - European Journal of Physiology. 2019;471(7):949-59. https://doi.org/10.1007/s00424-019-02273-4
61. Burtscher J, Hüfner K, Gatterer H, Pichler-Hefti J, Hefti U, Tannheimer M, et al. Time requirements of pre-acclimatization at simulated altitude to prevent acute mountain sickness. Journal of Travel Medicine. 2026;33(3). https://doi.org/10.1093/jtm/taag009
62. Zachar C, Grissom CK, McIntosh SE, Luks AM. Hypoxic Training Systems for Climbing at Extremely High Altitude: A Survey of Current Practice. High Altitude Medicine & Biology. 2025;0(0):15578682251384844. https://doi.org/10.1177/15578682251384844
63. Berger MM, Macholz F, Mairbäurl H, Bärtsch P. Remote ischemic preconditioning for prevention of high-altitude diseases: fact or fiction? J Appl Physiol (1985). 2015;119(10):1143-51. https://doi.org/10.1152/japplphysiol.00156.2015
64. Wang Z, Lv B, Zhang L, Gao R, Zhao W, Wang L, et al. Repeated remote ischaemic preconditioning can prevent acute mountain sickness after rapid ascent to a high altitude. Eur J Sport Sci. 2022;22(8):1304-14. https://doi.org/10.1080/17461391.2021.1927197
65. Wang B, Chen S, Song JY, Huang D, Xiao G. Recent advances in predicting acute mountain sickness: from multidimensional cohort studies to cutting-edge model applications. Frontiers in Physiology. 2024;15. https://doi.org/10.3389/fphys.2024.1397280
66. Yang M, Wu Y, Yang XB, Liu T, Zhang Y, Zhuo Y, et al. Establishing a prediction model of severe acute mountain sickness using machine learning of support vector machine recursive feature elimination. Sci Rep. 2023;13(1):4633. https://doi.org/10.1038/s41598-023-31797-0
67. Liu B, Huang H, Wu G, Xu G, Sun B-D, Zhang E-L, et al. A Signature of Circulating microRNAs Predicts the Susceptibility of Acute Mountain Sickness. Frontiers in Physiology. 2017;Volume 8 - 2017. https://doi.org/10.3389/fphys.2017.00055
68. Wang L, Xiao R, Chen J, Zhu L, Shi D, Wang J. A slow feature based LSTM network for susceptibility assessment of acute mountain sickness with heterogeneous data. Biomedical Signal Processing and Control. 2023;80:104355. https://doi.org/10.1016/j.bspc.2022.104355
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