Body Composition and Endocrine Adaptations to High-Altitude Trekking in the Himalayas

  • Gerardo Bosco
  • Antonio Paoli
  • Alex Rizzato
  • Giuseppe Marcolin
  • Maria Teresa Guagnano
  • Christian Doria
  • Suwas Bhandari
  • Tiziana Pietrangelo
  • Vittore VerrattiEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1211)


Long-term exposure to high altitude causes adaptive changes in several blood biochemical markers along with a marked body mass reduction involving both the lean and fat components. The aim of this study was to evaluate the impact of extended physical strain, due to extensive trekking at high altitude, on body composition, selected biomarkers in the blood, and the protective role of a high-protein diet in muscle dysfunction. We found that physical strain at high altitude caused a significant reduction in body mass and body fat, with a concomitant increase in the cross-sectional area of thigh muscles and an unchanged total lean body mass. Further, we found reductions in plasma leptin and homocysteine, while myoglobin, insulin, and C-reactive protein significantly increased. Creatine kinase, lactate dehydrogenase, and leptin normalized per body fat were unchanged. These findings demonstrate that high-altitude hypoxia, involving extended physical effort, has an impact on muscle function and body composition, facilitating sarcopenia and affecting body mass and fat distribution. It also activates pro-inflammatory metabolic pathways in response to muscular distress. These changes can be mitigated by a provision of a high-protein diet.


Adaptation Blood biomarkers Body composition High altitude Hypoxia Inflammatory response Trekking 



Our thanks go to all the porters and Sherpas, whose role was crucial to the success of this scientific project.

Competing Interests

The authors declare no competing interests in relation to this article.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of “G. D’Annunzio” University of Chieti-Pescara in Italy.

Subjects’ Consent

Written informed consent was obtained from all individual participants included in the study.


  1. Bailey DM, Davies B, Baker J (2000) Training in hypoxia: modulation of metabolic and cardiovascular risk factors in men. Med Sci Sports Exerc 32(6):1058–1066PubMedGoogle Scholar
  2. Baird MF, Graham SM, Baker JS, Bickerstaff GF (2012) Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery. J Nutr Metab 2012:960363PubMedPubMedCentralGoogle Scholar
  3. Benso A, Broglio F, Aimaretti G, Lucatello B, Lanfranco F, Ghigo E, Grottoli S (2007) Endocrine and metabolic responses to extreme altitude and physical exercise in climbers. Eur J Endocrinol 157(6):733–740PubMedGoogle Scholar
  4. Beretta E, Lanfranconi F, Grasso GS, Bartesaghi M, Alemayehu HK, Pratali L, Catuzzo B, Giardini G, Miserocchi G (2017) Air blood barrier phenotype correlates with alveolo–capillary O2 equilibration in hypobaric hypoxia. Respir Physiol Neurobiol 246:53–58PubMedGoogle Scholar
  5. Boos CJ, Hodkinson PD, Mellor A, Green NP, Bradley D, Greaves K, Woods DR (2013) The effects of prolonged acute hypobaric hypoxia on novel measures of biventricular performance. Echocardiography 30(5):534–541PubMedGoogle Scholar
  6. Bosco G, Ionadi A, Panico S, Faralli F, Gagliardi R, Data P, Mortola JP (2003) Effects of hypoxia on the circadian patterns in men. High Alt Med Biol 4(3):305–318PubMedGoogle Scholar
  7. Bosco G, Verratti V, Fanò G (2010) Performances in extreme environments: effects of hyper/hypobarism and hypogravity on skeletal muscle. Eur J Translat Myol 20(3):83–90Google Scholar
  8. Broglio F, Prodam F, Riganti F, Muccioli G, Ghigo E (2006) Ghrelin: from somatotrope secretion to new perspectives in the regulation of peripheral metabolic functions. Front Horm Res 35:102–114PubMedGoogle Scholar
  9. Cacciani N, Paoli A, Reggiani C, Patruno M (2008) Hypoxia: the third wheel between nerve and muscle. Neurol Res 30(2):149–154PubMedGoogle Scholar
  10. di Cerretelli P, Prampero PE (1987) Gas exchange at exercise. In: Farhi LE, Tenney SM (eds) Handbook of physiology. the respiratory system IV. American Physiological Society, Bethesda, pp 555–632Google Scholar
  11. Di Giulio C, Bianchi G, Cacchio M, Artese L, Piccirilli M, Verratti V, Valerio R, Iturriaga R (2006) Neuroglobin, a new oxygen binding protein is present in the carotid body and increases after chronic intermittent hypoxia. Adv Exp Med Biol 580:15–19PubMedGoogle Scholar
  12. Doria C, Toniolo L, Verratti V, Cancellara P, Pietrangelo T, Marconi V, Paoli A, Pogliaghi S, Fanò G, Reggiani C, Capelli C (2011) Improved VO2 uptake kinetics and shift in muscle fiber type in high–altitude trekkers. J Appl Physiol 111(6):1597–1605PubMedGoogle Scholar
  13. Durnin JV, Womersley J (1974) Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br J Nutr 32:77–97PubMedGoogle Scholar
  14. Hartmann G, Tschöp M, Fischer R, Bidlingmaier C, Riepl R, Tschöp K, Hautmann H, Endres S, Toepfer M (2000) High altitude increases circulating interleukin–6, interleukin–1 receptor antagonist and C–reactive protein. Cytokine 12:246–252PubMedGoogle Scholar
  15. Hoppeler H, Vogt M (2001) Muscle tissue adaptations to hypoxia. J Exp Biol 204(Pt 18):3133–3139PubMedGoogle Scholar
  16. Housh DJ, Housh TJ, Weir JP, Weir LL, Johnson GO, Stout JR (1995) Anthropometric estimation of thigh muscle cross–sectional area. Med Sci Sports Exerc 27(5):784–791PubMedGoogle Scholar
  17. Hultgren HN (1978) High–altitude edema. JAMA 239(21):2239PubMedGoogle Scholar
  18. Kylhammar D, Rådegran G (2017) The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension. Acta Physiol (Oxf) 219(4):728–756Google Scholar
  19. Larsen JJ, Hansen JM, Olsen NV, Galbo H, Dela F (1997) The effect of altitude hypoxia on glucose homeostasis in men. J Physiol 504(1):241–249PubMedPubMedCentralGoogle Scholar
  20. Li JJ, Fang CH (2004) C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses 62(4):499–506PubMedGoogle Scholar
  21. Luks AM, Levett D, Martin DS, Goss CH, Mitchell K, Fernandez BO, Feelisch M, Grocott MP, Swenson ER, Investigators CXE (2017) Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5300 m). Exp Physiol 102(6):711–724PubMedGoogle Scholar
  22. Mancinelli R, Di Filippo ES, Verratti V, Fulle S, Toniolo L, Reggiani C, Pietrangelo T (2016) The regenerative potential of female skeletal muscle upon hypobaric hypoxic exposure. Front Physiol 7:303PubMedPubMedCentralGoogle Scholar
  23. Mariggiò MA, Falone S, Morabito C, Guarnieri S, Mirabilio A, Pilla R, Bucciarelli T, Verratti V, Amicarelli F (2010) Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude. High Alt Med Biol 11(4):333–342PubMedGoogle Scholar
  24. Moore LG, Zamudio S, Zhuang J, Droma T, Shohet RV (2002) Analysis of the myoglobin gene in Tibetans living at high altitude. High Alt Med Biol 3(1):39–47PubMedGoogle Scholar
  25. Nedergaard A, Karsdal MA, Sun S, Henriksen K (2013) Serological muscle loss biomarkers: an overview of current concepts and future possibilities. J Cachexia Sarcopenia Muscle 4(1):1–17PubMedGoogle Scholar
  26. Palmer BF, Clegg DJ (2014) Ascent to altitude as a weight loss method: the good and bad of hypoxia inducible factor activation. Obesity (Silver Spring) 22(2):311–317Google Scholar
  27. Paoli A, Bianco A, Damiani E, Bosco G (2014) Ketogenic diet in neuromuscular and neurodegenerative diseases. Biomed Res Int 2014(474296):1Google Scholar
  28. Paoli A, Bosco G, Camporesi EM, Mangar D (2015) Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol 6:27PubMedPubMedCentralGoogle Scholar
  29. Pelliccione F, Verratti V, D’Angeli A, Micillo A, Doria C, Pezzella A, Iacutone G, Francavilla F, Di Giulio C, Francavilla S (2011) Physical exercise at high altitude is associated with a testicular dysfunction leading to reduced sperm concentration but healthy sperm quality. Fertil Steril 96(1):28–33PubMedGoogle Scholar
  30. Petousi N, Croft QP, Cavalleri GL, Cheng HY, Formenti F, Ishida K, Lunn D, McCormack M, Shianna KV, Talbot NP, Ratcliffe PJ, Robbins PA (2014) Tibetans living at sea level have a hyporesponsive hypoxia-inducible factor system and blunted physiological responses to hypoxia. J Appl Physiol 116(7):893–904PubMedGoogle Scholar
  31. Pugh LG (1962) Physiological and medical aspects of the Himalayan scientific and mountaineering expedition, 1960–61. Br Med J 2(5305):621–627PubMedPubMedCentralGoogle Scholar
  32. Richalet JP (2010) Operation Everest III: COMEX ’97. High Alt Med Biol 11(2):121–132PubMedGoogle Scholar
  33. Rose MS, Houston CS, Fulco CS, Coates G, Sutton JR, Cymerman A (1988) Operation Everest. II: nutrition and body composition. J Appl Physiol 65(6):2545–2551PubMedGoogle Scholar
  34. San T, Polat S, Cingi C, Eskiizmir G, Oghan F, Cakir B (2013) Effects of high altitude on sleep and respiratory system and theirs adaptations. ScientificWorldJournal 2013:241569PubMedPubMedCentralGoogle Scholar
  35. Sumi D, Kojima C, Goto K (2018) Impact of endurance exercise in hypoxia on muscle damage, inflammatory and performance responses. J Strength Cond Res 32(4):1053–1062PubMedGoogle Scholar
  36. Vats P, Singh VK, Singh SN, Singh SB (2007) High altitude induced anorexia: effect of changes in leptin and oxidative stress levels. Nutr Neurosci 10(5–6):243–249PubMedGoogle Scholar
  37. Verhoef P, van Vliet T, Olthof MR, Katan MB (2005) A high–protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers. Am J Clin Nutr 82(3):553–558PubMedGoogle Scholar
  38. Verratti V, Di Giulio C, Bianchi G, Cacchio M, Petruccelli G, Artese L, Lahiri S, Iturriaga R (2009) Neuroglobin in aging carotid bodies. Adv Exp Med Biol 648:191–195PubMedGoogle Scholar
  39. Verratti V, Falone S, Fanò G, Paoli A, Reggiani C, Tenaglia R, Di Giulio C (2011) Effects of hypoxia on nocturnal erection quality: a case report from the Manaslu expedition. J Sex Med 8(8):2386–2390PubMedGoogle Scholar
  40. Verratti V, Falone S, Doria C, Pietrangelo T, Di Giulio C (2015) Kilimanjaro Abruzzo expedition: effects of high–altitude trekking on anthropometric, cardiovascular and blood biochemical parameters. Sport Sci Health 11(3):271–278PubMedPubMedCentralGoogle Scholar
  41. Verratti V, Ietta F, Paulesu L, Romagnoli R, Ceccarelli I, Doria C, Fanò Illic G, Di Giulio C, Aloisi AM (2017) Physiological effects of high–altitude trekking on gonadal, thyroid hormones and macrophage migration inhibitory factor (MIF) responses in young lowlander women. Phys Rep 5(20):e13400. CrossRefGoogle Scholar
  42. West JB (2012) High–altitude medicine. Am J Respir Crit Care Med 186(12):1229–1237PubMedGoogle Scholar
  43. Westerterp-Plantenga MS, Westerterp KR, Rubbens M, Verwegen CR, Richalet JP, Gardette B (1999) Appetite at “high altitude” [Operation Everest III (Comex-’97)]: a simulated ascent of Mount Everest. J Appl Physiol 87:391–399PubMedGoogle Scholar
  44. Woo J (2018) Nutritional interventions in sarcopenia: where do we stand? Curr Opin Clin Nutr Metab Care 21(1):19–23PubMedGoogle Scholar
  45. Yanai H (2015) Nutrition for sarcopenia. J Clin Med Res 7(12):926–931PubMedPubMedCentralGoogle Scholar
  46. Zhang MH (2012) Rhabdomyolosis and its pathogenesis. World J Emerg Med 3(1):11–15PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Gerardo Bosco
    • 1
  • Antonio Paoli
    • 1
  • Alex Rizzato
    • 1
  • Giuseppe Marcolin
    • 1
  • Maria Teresa Guagnano
    • 2
  • Christian Doria
    • 3
  • Suwas Bhandari
    • 4
  • Tiziana Pietrangelo
    • 5
  • Vittore Verratti
    • 6
    Email author
  1. 1.Department of Biomedical SciencesUniversity of PadovaPadovaItaly
  2. 2.Department of Medicine and Aging“G. D’Annunzio” University of Chieti-PescaraChietiItaly
  3. 3.Department of Biomedical Sciences for HealthUniversity of MilanMilanItaly
  4. 4.Department of Critical Care and Internal MedicineSecond Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
  5. 5.Department of Neuroscience, Imaging and Clinical Sciences“G. D’Annunzio” University of Chieti-PescaraChietiItaly
  6. 6.Department of Psychological SciencesHealth and Territory “G. D’Annunzio” University of Chieti-PescaraChietiItaly

Personalised recommendations