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EPO, red cells, and serum transferrin receptor in continuous and intermittent hypoxia


Medicine & Science in Sports & Exercise: April 2000 - Volume 32 - Issue 4 - pp 800-804
BASIC SCIENCES: Original Investigations: Symposium: The role of skeletal muscles in lactate exchange during exercise

KOISTINEN, P. O., H. RUSKO, K. IRJALA, A. RAJAMÄKI, K. PENTTINEN, V-P. SARPARANTA, J. KARPAKKA, and J. LEPPÄLUOTO. EPO, red cells, and serum transferrin receptor in continuous and intermittent hypoxia. Med. Sci. Sports Exerc., Vol. 32, No. 4, pp. 800–804, 2000.

Purpose: Erythropoietic response in 10 healthy nonsmoking volunteers exposed to normobaric hypoxia continuously or intermittently 12 h daily for 7 d was evaluated in a randomized cross-over study.

Methods: An oxygen content of 15.4% corresponding to an altitude of 2500 m was created by adding nitrogen into room air in a flat. Venous blood samples for hemoglobin (Hb), hematocrit (Hct), reticulocytes, serum erythropoietin (S-EPO), red cell 2,3-diphosphoglycerate (2,3-DPG), serum ferritin (S-Ferrit), and serum soluble transferrin receptor (S-TransfR) were drawn at 8:00 a.m.

Results: S-EPO was increased from baseline values of 22.9 ± 9.6 and 20.5 ± 10.1 U·L−1 to 40.7 ± 12.9 (P < 0.05) and 35 ± 14.3 U·L−1 (P < 0.05) after the first night in continuous and intermittent hypoxia, respectively, and remained elevated throughout both exposures. Hb and Hct values did not show any significant changes. Red cell 2,3-DPG rose from baseline a value of 5.0 ± 0.8 to 5.9 ± 0.7 mmol·L−1 (P < 0.05) after the first day in continuous hypoxia and from 5.2 ± 0.7 mmol·L−1 to 6.1 ± 0.5 mmol·L−1 on day 3 (P < 0.05) during intermittent hypoxia. The reticulocyte count rose significantly (P < 0.05) after 5 d in both experiments. S-transferrin receptor level rose significantly from 2.2 ± 0.4 and 2.1 ± 0.5 mg·L−1 to 2.6 ± 0.5 mg·L−1 and 2.3 ± 0.6 mg·L−1 on day 5 (P < 0.05), to 2.7 ± 0.5 mg·L−1 and 2.5 ± 0.6 mg·L−1 on day 7 (P < 0.05) under continuous and intermittent hypoxia, respectively.

Conclusions: We suggest that intermittent exposure to moderate normobaric hypoxia 12 h daily for 1 wk induces a similar stimulation of erythropoiesis as continuous exposure.

Exposure to hypoxic environment results in an acceleration of erythropoiesis that depends on the intensity and duration of the hypoxic exposure (3,4,7). A significant increase in plasma erythropoietin levels has been observed already after a 114-min exposure to normobaric or hypobaric hypoxia (FIO2 0.105 and 460–520 Torr), respectively (7,19). The rate of change from normoxic to hypoxic conditions also plays an important role in physiological responses to acute environmental hypoxia (12). Both clinical and experimental data show that even intermittent hypoxia stimulates erythropoietin production in humans (19,31) and rats (26). It has been proposed that “living high, training low” would be the best strategy to improve physical performance, by avoiding the detrimental effects of reduced training intensity at hypoxic conditions while retaining the benefits of altitude acclimatization (22). Intermittent normobaric hypoxia has recently been used by endurance athletes to stimulate erythropoiesis and to improve physical performance (28,29).

When training is performed under normoxic conditions, it is crucial that the intervening hypoxic exposures stimulate erythropoiesis to such an extent that the number of red cells increases (29). There are, however, no studies comparing the stimulation of erythropoiesis in continuous and intermittent normobaric hypoxia in man. Serum soluble transferrin receptor reflects the rate of erythropoiesis (2,15) in healthy iron-repleted subjects. The measurement of serum transferrin receptor gives a feasible noninvasive method for the estimation of erythropoietic activity in bone marrow. This is further strengthened by simultaneous measurements of serum erythropoietin (2).

We undertook this randomized cross-over study in order to evaluate stimulation of erythropoiesis at normobaric hypoxia under prolonged continuous or repetitive intermittent exposures. Serum soluble transferrin receptor and erythropoietin measurements were used as indicators of erythropoietic activity.

Health Center Hospital of Oulu, FINLAND; Research Institute for Olympic Sports, Jyväskylä, FINLAND; Department of Clinical Chemistry and Hematology, University of Turku, FINLAND; and Vuokatti Sports and Training Center, FINLAND; Department of Sports Medicine, Deaconess Institute, Oulu, FINLAND; Kainuu Central Hospital, Kajaani, FINLAND; and Department of Physiology, University of Oulu, FINLAND

Submitted for publication August 1997.

Accepted for publication August 1998.

Address for correspondence: Dr. Pentti Koistinen, Health Center Hospital of Oulu, Box 8, SF-90015 Oulu, Finland; E-mail:

©2000The American College of Sports Medicine