Low haemoglobin concentration in Tibetan males is associated with greater high‐altitude exercise capacity

Abstract

Tibetans living at high altitude have adapted genetically such that many display a low erythropoietic response, resulting in near sea-level haemoglobin (Hb) concentration. We hypothesized that absence of the erythropoietic response would be associated with greater exercise capacity compared to those with high [Hb] as a result of beneficial changes in oxygen transport. We measured, in 21 Tibetan males with [Hb] ranging from 15.2 g dl(-1) to 22.9 g dl(-1) (9.4 mmol l(-1) to 14.2 mmol l(-1) ), [Hb], ventilation, volumes of O2 and CO2 utilized at peak exercise (V̇O2 and V̇CO2), heart rate, cardiac output and arterial blood gas variables at peak exercise on a cycle ergometer at ∼4200 m. Lung and muscle O2 diffusional conductances were computed from these measurements. [Hb] was related (negatively) to V̇O2 kg(-1) (r = -0.45, P< 0.05), cardiac output kg(-1) (QT kg(-1) , r = -0.54, P < 0.02), and O2 diffusion capacity in muscle (DM kg(-1) , r = -0.44, P<0.05), but was unrelated to ventilation, arterial partial pressure of O2 (PaO2) or pulmonary diffusing capacity. Using multiple linear regression, variance in peak V̇O2 kg(-1) was primarily attributed to QT, DM, and PCO2 (R(2) = 0.88). However, variance in pulmonary gas exchange played essentially no role in determining peak V̇O2. These results (1) show higher exercise capacity in Tibetans without the erythropoietic response, supported mostly by cardiac and muscle O2 transport capacity and ventilation rather than pulmonary adaptations, and (2) support the emerging hypothesis that the polycythaemia of altitude, normally a beneficial response to low cellular PO2, may become maladaptive if excessively elevated under chronic hypoxia. The cause and effect relationships among [Hb], QT, DM, and PCO2 remain to be elucidated.

Adaptive genetic changes related to haemoglobin concentration in native high‐altitude Tibetans

“…Clearly, relatively lower [Hb], while a hallmark of Tibetan physiology and of recent focus in the high‐altitude genomics literature, is not the only factor involved in Tibetan adaptation and may influence or be the result of changes at one or more steps of the oxygen transport system (Simonson et al . ; Wagner et al . ).…”

Human genetic adaptation to high altitudes: Current status and future prospects

“…The Andeans’ increased lung O 2 diffusion, as reviewed above, is a developmental response that is largely recapitulated in persons without multigenerational residence at high altitude but who themselves were born and raised at high altitude. Unknown is whether the Tibetans’ improved tissue O 2 diffusion and utilization (Holden et al, 1995; Simonson et al, 2015) also occur with lifelong residence. With respect to comparisons among native high-altitude populations, the relatively small number of studies in Ethiopian highlanders makes three-way comparisons difficult but several comprehensive reviews of Andeans and Tibetans have been published (Beall et al, 1990; Bigham and Lee, 2014; Gilbert-Kawai et al, 2014; Holden et al, 1995; Moore, 2001; Moore et al, 1998b; Simonson, 2015; Simonson et al, 2015; Winslow et al, 1989).…”

“…Unknown is whether the Tibetans’ improved tissue O 2 diffusion and utilization (Holden et al, 1995; Simonson et al, 2015) also occur with lifelong residence. With respect to comparisons among native high-altitude populations, the relatively small number of studies in Ethiopian highlanders makes three-way comparisons difficult but several comprehensive reviews of Andeans and Tibetans have been published (Beall et al, 1990; Bigham and Lee, 2014; Gilbert-Kawai et al, 2014; Holden et al, 1995; Moore, 2001; Moore et al, 1998b; Simonson, 2015; Simonson et al, 2015; Winslow et al, 1989). To summarize, Tibetans compared to Andeans have higher V E at rest and during exercise, marginally lower lung volumes and diffusing capacities, similar levels of SaO 2 , lower Hb concentrations, less hypoxic pulmonary vasoconstriction and hence lower Ppa pressures (Figure 4B), and perhaps better preservation of cardiac function, exercise performance, O 2 diffusion to the muscle and tissue O 2 utilization.…”

“…Helpful in this regard is a recent study showing that healthy Tibetan men with lower Hb levels had greater VO 2 max as the result of greater cardiac output and muscle O 2 diffusion capacity, although such relationships were not specific to Tibetans but also observed among Han residents of high altitude exhibiting a limited range of Hb concentrations (Simonson et al, 2015). Raising the possibility that differences in Hb levels during adulthood reflect earlier lifetime events, Julian and co-workers showed that young Andean men with modestly-elevated Hb had more often been hypoxic in utero or during neonatal life (Julian et al, 2015), and showed early signs of pulmonary vascular dysfunction and intermittent hypoxia during sleep (Julian et al, 2013).…”

Sea‐level haemoglobin concentration is associated with greater exercise capacity in Tibetan males at 4200 m

“…For instance, it is currently unclear whether selection directly acted upon [Hb] to mitigate potentially maladaptive outcomes of elevated red cell numbers or if low [Hb] is the consequence of other antecedent adaptive changes (Moore, 2001;Beall et al 2007;Storz, 2010;Simonson et al 2015). Thus, the development of low [Hb] may be secondary to adaptation of other (as yet unexplored) targets important to exercise and O 2 transport, rather than the primary adaptive event.…”