Pro: All Dwellers at High Altitude Are Persons of Impaired Physical and Mental Powers

“The acclimatised man is not the man who has attained to bodily and mental powers as great in Cerro de Pasco as he would have in Cambridge (whether that town be situated in Massachusetts or in England). Such a man does not exist. All dwellers of high altitude are persons of impaired physical and mental powers” (Barcroft, 1925).

Barcroft's statement should be seen in context; at that time little was known about acclimatization and adaptation to altitude. He wrote it upon return from Cerro de Pasco in Peru, where he investigated lowlander acclimatization in 1921–1922, but also collected data from Andean highlanders. As John West writes in the editorial to this Pro/Con topic (West, 2013), the Peruvian physician and scientist Carlos Monge strongly disagreed with Barcroft's statement, as applied to Andean highlanders, even though Barcroft also reported to be impressed by the extraordinary physical performance of the altitude natives as compared to the acclimatizing lowlanders of his expedition.

But given what we know today, was Barcroft right? What are the effects of altitude on physical and mental powers? And do they affect any human—lowlander or highlander—to the same extent? I was asked to take position to Barcroft's statement on 'impaired physical […] power'. My view is that altitude hypoxia does indeed impair aerobic large muscle group physical performance (running or cycling), in everybody, lowlander or highlander. I do not discuss cognitive performance (see the Pro statement by Yan (2013) for that), but will argue that the impaired aerobic exercise performance at altitude is also related to effects of hypoxia on the central nervous system (CNS), especially so at altitudes beyond 4000–5000 m.

The 1968 Mexico City Olympic games held at 2240 m were very illustrative for the effects of altitude on physical performance. Explosive type activities were not affected, or in some cases even positively, when involving athletes (or objects) moving through the air, benefiting from the lower air density at altitude (Girard, 2012; Mureika, 2006). But endurance sports were clearly adversely affected (McFarland, 1986). There are three metabolic pathways to provide energy to do work: the aerobic pathway and the alactic and lactic anaerobic pathways. For walking, running, or climbing, all energy is derived from substrate oxidation. But at the onset of effort, and during short duration explosive or sprint-type efforts, the alactic (phosphocreatine) and lactic (anaerobic glycolysis) pathways can temporarily provide the energy necessary for the effort. During maximum efforts, this reaches intensities well over the aerobically sustainable maximum. The incurred oxygen deficit is paid afterwards upon cessation of the effort. This explains why explosive power (like vertical jumping) does not change at altitude, as long as the muscle remains intact (Ferretti et al., 2008), and why stationary sprinting type efforts such as Wingate tests are also hardly affected by hypoxia (Calbet et al., 2003; Robach et al., 1997). Only at extreme altitudes approaching the summit of Everest do explosive type efforts become somewhat limited, presumably because of the profound cerebral hypoxia (Amann and Kayser, 2009; Millet et al., 2012).

Endurance performance is impaired already at quite moderate altitude. This is because the capacity for endurance activities depends heavily on the maximum oxygen flux through the system from inspired air to the mitochondria. This Vo_2max is highly sensitive to even small reductions in arterial oxygenation. Exercise-induced arterial hypoxemia (Dempsey and Wagner, 1999) impairs endurance exercise performance, even at sea level (Nielsen, 2003) and these phenomena are amplified when the inspired oxygen pressure drops (Amann and Calbet, 2008). Those with a high Vo_2max lose more than untrained subjects, and the absolute difference in aerobic power becomes more shallow the greater the degree of hypoxia (Ferretti et al., 1997; Marconi et al., 2004; Mollard et al., 2007). This relates to a greater drop in SaO₂ and consequently Cao₂ and Qao₂ at maximum exercise in the trained (Amann and Calbet, 2008). At moderate altitudes there is some effect of acclimatization (Schuler et al., 2007) but at higher altitudes Vo_2max does not improve much with time, despite the increase in Cao₂ from ventilatory acclimatization and the erythropoiesis-induced higher Hb concentration (Cerretelli, 1976; Jacobs et al., 2012).

Important still unexplained findings are the lower maximum heart rate and cardiac output in severe hypoxia, when Sao₂ drops below 80%, and the almost instant relief from the intolerable sensation of exertion at peak effort in such hypoxia by acutely increasing inspired oxygen tension to normoxic levels, allowing the effort to be continued and heart rate to increase (Amann and Kayser, 2009). This suggests that severe hypoxia limits motor drive, reminding us of an often forgotten but obvious tenet stating that any exercise begins and ends in the brain through the recruitment and derecruitment of motor units (Kayser, 2003).

So how do altitude natives do in comparison to lowlanders? Anecdotal accounts of extraordinary capacity of altitude natives to do hard work at altitude are countless. One can think of altitude miners in the Andes or of Sherpas having repeatedly climbed Everest without bottled oxygen. But their V'o_2max is in fact not that much different from that of acclimatized lowlanders of similar training level (Chen et al., 1997; Lundby et al., 2004; Marconi et al., 2004; Marconi et al., 2006; Niu et al., 1995; Wagner et al. 2002). Interestingly, highlanders do not gain as much in acute normoxia as acclimatized lowlanders (Favier et al., 1995; Wagner et al., 2002). But V'o_2max is not a perfect predictor of submaximal endurance performance. For submaximum endurance efforts, the scant evidence available would suggest some advantage for highlanders for sustaining high fractions of their aerobic capacity before becoming exhausted, and improved metabolic efficiency, allowing more work to be performed for a given amount of oxygen consumed (Cerretelli et al., 2009; Marconi et al., 2006).

So why would highlanders do better at altitude? Differences between highlanders and lowlanders can be due to developmental effects (being born and brought up at altitude) and to genetic differences that convey an altitude advantage (Brutsaert, 2008), and both seem to play a role. For example, Andean highlanders have greater lung volumes as a result of childhood exposure to hypoxia and a genetic trait, which brings higher pulmonary diffusion capacity (Brutsaert et al., 2004). Exposure of lowland-born Tibetans—no developmental exposure to altitude—to 5050 m showed that they fared better than lowlanders, indicating that childhood exposure is not a prerequisite for some advantages (Marconi et al., 2004). In recent years, a flurry of genetic studies have brought accumulating genetic evidence corroborating those physiological observations. There is an important genetic component to altitude adaptation and exposure over many generations led to the selection of alleles in Andean (Brutsaert et al., 2004), Himalayan (Simonson et al., 2012), and East-African natives (Scheinfeldt et al., 2012).

But also lowlanders who do well at altitude, as compared to less well-off lowlanders, may do so because of genetic traits. One example are the angiotensin converting enzyme (ACE) gene polymorphisms of which the I allele may relate to endurance and, perhaps, extreme altitude climbing success (Puthucheary et al. 2011).

But why do Tibetans do so well at endurance exercise at altitude? Investigating limitation of aerobic exercise performance in hypoxia in lowlanders, Naeije et al. (2010) suggested that hypoxic pulmonary vasoconstriction (HPV) may play a role. It would lead to pulmonary hypertension, right ventricular overload, limiting cardiac output, impairing maximum oxygen transport and performance. A recent Pro/Con in the journal was devoted to this hypothesis (Anholm and Foster, 2011; Naeije, 2011). Tibetans have much less HPV as lowlanders (Groves et al., 1993) and less performance decrement in hypoxia compared to others (Marconi et al., 2004; Niu et al., 1995). They also have better saturations at rest and during exercise, only partly explained by the higher ventilations (Marconi et al., 2004; Wu and Kayser, 2006). To investigate this further, with colleagues from Xining, China, we recently compared Tibetans to Han Chinese, both living at 2300 m (Kayser et al., 2013). We had them both do incremental uphill treadmill running at the equivalent of an altitude of 5000 m in a hypobaric chamber, under placebo versus inhaled furosemide (to decrease afferent vagal traffic from pulmonary receptors), or iloprost (to decrease HPV). The Tibetans desaturated less and reached similar maximum heart rates at 2300 m and 5000 m, independent of the intervention, reaching peak heart rates>200 bpm, while Han Chinese had much lower heart rates at 5000 m compared to 2300 m. In the Han, furosemide partially restored maximum heart rate; iloprost improved performance and made them more similar to Tibetans with regard to peak aerobic performance in severe hypoxia. HPV and right ventricular function may thus play a role in limiting maximum aerobic performance in severe hypoxia. Since aerobic performance remains nevertheless reduced at 5000 m in both Tibetans and Han Chinese after intervention, additional mechanisms are involved in the reduction of maximum aerobic exercise capacity in conditions of severe hypoxia.

In conclusion, without doubt the hypoxia of high altitude impairs physical performance. But the extent varies with altitude, degree of acclimatization, history of exposure, and last but not least, genetic endowment of the individual. Surely (healthy) high altitude natives are somewhat better off as compared to lowlanders, but anybody climbing up the slopes of Andean or Himalayan giants will be progressively moving more slowly, eventually almost coming to a standstill when reaching the top of Everest. Not just because there is no higher place to go, but also because maximum aerobic capacity on top of Everest is barely sufficient to still do some slow walking. Had the mountain been higher, or at a more northern latitude, it might well not have been climbable without supplementary bottled oxygen, by any human, from whatever ethnic origin; an irrelevant, but quite an extraordinary coincidence of nature.