Iron insufficiency diminishes the erythropoietic response to moderate altitude exposure

J Appl Physiol (1985). 2019 Dec 1;127(6):1569-1578. doi: 10.1152/japplphysiol.00115.2018. Epub 2019 Oct 31.


The effects of iron stores and supplementation on erythropoietic responses to moderate altitude in endurance athletes were examined. In a retrospective study, red cell compartment volume (RCV) responses to 4 wk at 2,500 m were assessed in athletes with low (n = 9, ≤20 and ≤30 ng/mL for women and men, respectively) and normal (n = 10) serum ferritin levels ([Ferritin]) without iron supplementation. In a subsequent prospective study, the same responses were assessed in athletes (n = 26) with a protocol designed to provide sufficient iron before and during identical altitude exposure. The responses to a 4-wk training camp at sea level were assessed in another group of athletes (n = 13) as controls. RCV and maximal oxygen uptake (V̇o2max) were determined at sea level before and after intervention. In the retrospective study, athletes with low [Ferritin] did not increase RCV (27.0 ± 2.9 to 27.5 ± 3.8 mL/kg, mean ± SD, P = 0.65) or V̇o2max (60.2 ± 7.2 to 62.2 ± 7.5 mL·kg-1·min-1, P = 0.23) after 4 wk at altitude, whereas athletes with normal [Ferritin] increased both (RCV: 27.3 ± 3.1 to 29.8 ± 2.4 mL/kg, P = 0.002; V̇o2max: 62.0 ± 3.1 to 66.2 ± 3.7 mL·kg-1·min-1, P = 0.003). In the prospective study, iron supplementation normalized low [Ferritin] observed in athletes exposed to altitude (n = 14) and sea level (n = 6) before the altitude/sea-level camp and maintained [Ferritin] within normal range in all athletes during the camp. RCV and V̇o2max increased in the altitude group but remained unchanged in the sea-level group. Finally, the increase in RCV correlated with the increase in V̇o2max [(r = 0.368, 95% confidence interval (CI): 0.059-0.612, P = 0.022]. Thus, iron deficiency in athletes restrains erythropoiesis to altitude exposure and may preclude improvement in sea-level athletic performance.NEW & NOTEWORTHY Hypoxic exposure increases iron requirements and utilization for erythropoiesis in athletes. This study clearly demonstrates that iron deficiency in athletes inhibits accelerated erythropoiesis to a sojourn to moderate high altitude and may preclude a potential improvement in sea-level athletic performance with altitude training. Iron replacement therapy before and during altitude exposure is important to maximize performance gains after altitude training in endurance athletes.

Keywords: anemia; ferritin; long-distance running; red cell mass.

MeSH terms

  • Acclimatization / physiology*
  • Adult
  • Altitude
  • Athletes
  • Athletic Performance / physiology
  • Erythropoiesis / physiology*
  • Female
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia / physiopathology*
  • Iron / metabolism*
  • Male
  • Oxygen Consumption / physiology
  • Physical Endurance / physiology
  • Prospective Studies
  • Retrospective Studies
  • Young Adult


  • Iron