Exercise is medicine for chronic mountain sickness

It is estimated that > 80 million people live above 2,500 m a.s.l. worldwide (Tremblay & Ainslie, 2021). Chronic exposure to low levels of oxygen causes several physiological adaptations and has been an active area of investigation for well over 100 years. However, ∼5–10% of individuals living at high altitude develop chronic mountain sickness (CMS), a syndrome characterized by hypoxaemia, excessive erythrocytosis and increased blood viscosity, which has several adverse neurological and cerebrovascular consequences (León-Velarde et al. 2005; Villafuerte & Corante, 2016). The incidence of CMS increases with elevation and with advancing age, with as many as one-third of older Andeans exhibiting CMS (Monge et al. 1989). Current treatments for CMS include therapeutic phlebotomy (bloodletting) and descent to lower altitudes. Phlebotomy has been shown to reduce haematocrit, improve oxygenation and, subsequently, to ameliorate CMS symptoms. Nonetheless, these improvements appear to be transient, receding a few weeks after the treatment (Villafuerte & Corante, 2016). In addition, the invasive nature of phlebotomy and the fact that it can also cause iron deficiency and induce pulmonary hypertension make it a difficult long-term treatment. Likewise, descent to lower altitudes or sea level is impractical for to social and economic reasons and is also not a permanent solution, because the CMS symptoms reappear after returning to a high altitude (León-Velarde et al. 2005; Villafuerte & Corante, 2016). A low-cost, non-invasive and non-pharmacological treatment for patients with CMS is currently unavailable. Regular physical exercise provides numerous physiological benefits, not only in healthy individuals, but also in a variety of clinical conditions. A previous report has demonstrated that native Andean athletes possess lower haematocrits than their sedentary counterparts (Cornolo et al. 2005). In this scenario, it is reasonable to speculate that exercise training could be beneficial for patients with CMS. Nevertheless, to date, the impact of exercise training on patients with CMS has not been studied. To fill this knowledge gap, in this issue of Experimental Physiology, Macarlupú et al. (2021) sought to determine the effects of moderate-intensity aerobic exercise training on markers of CMS in native Andean highlanders. Eight male participants diagnosed with CMS (pretraining haematocrit of ∼71%) performed 60 min of moderate-intensity cycling exercise (60% of peak oxygen uptake) 4 days per week for 8 weeks. The primary outcomes were the haematocrit and CMS signs and symptoms (Qinghai CMS questionnaire). Secondary outcomes included 24 h ambulatory blood pressure monitoring, in addition to blood levels of glucose, insulin, cholesterol and erythropoietin. Measurements were performed before and 4 and 8 weeks after exercise training. As expected, 8 weeks of moderate-intensity aerobic exercise increased the peak oxygen uptake by ∼10%, showing the effectiveness of the training protocol. In addition, exercise training decreased the haematocrit and CMS score, and these responses were already apparent after 4 weeks of training. The haematocrit decreased progressively by 5% and 7% and the CMS score decreased by ∼46% and ∼40% at weeks 4 and 8 of exercise training, respectively. In contrast, exercise training did not change 24 h blood pressure or resting glycaemia, insulinaemia, erythropoietin or lipid profile, with the exception of increased high-density lipoprotein–cholesterol after 8 weeks of exercise training. Collectively, these findings demonstrated that moderate-intensity aerobic exercise training can reduce haematocrit and alleviate symptoms of CMS in native Andean highlanders, providing the first evidence that exercise training might be used as a non-pharmacological therapy for CMS. It is important to consider that because the experiments were performed in young male Andeans, the impact of exercise training on female and/or older patients with CMS requires further investigation. In addition, Macarlupú et al. (2021) studied residents of Cerro de Pasco, Peru (4,340 m). Given that the prevalence and severity of CMS increase with elevation (León-Velarde et al. 2005; Villafuerte & Corante, 2016), the extent to which exercise training is effective in different highlander populations remains unknown. Furthermore, it is well accepted that different exercise intensities, frequencies and modalities (i.e., continuous aerobic, high-intensity interval training and resistance training) can induce different physiological responses and adaptations. Hence, future studies are required to determine the effects of different exercise training programmes in patients with CMS. Another open question is the impact of detraining on these patients. Do the haematocrit and CMS symptoms return to pretraining values after detraining? How long do the beneficial effects of 8 weeks of moderate-intensity aerobic training last? Notably, the mechanisms by which moderate-intensity aerobic training reduce haematocrit and CMS symptoms in native highlanders remain largely unknown. In conclusion, Macarlupú et al. (2021) are to be commended on performing a challenging training study in a unique clinical population. The authors not only advanced our current understanding on the beneficial effects of exercise training in patients with CMS, but also created new key research questions that broadly impact and determine the extent to which exercise training is medicine for patients with CMS. None declared.

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