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DOI: 10.1055/s-0031-1285221
Human intestinal and systemic adaptation of iron metabolism and transport to hypoxia in healthy mountaineers after rapid ascent to 4559m
Background & aims: Human iron metabolism is closely regulated by erythropoesis, oxygen homeostasis and intestinal iron absorption. The aim of this study was to characterize for the first time the adaptation of iron metabolism and transport to hypoxia under high altitude conditions in man at the levels of (i) intestinal iron uptake (ii) changes in systemic iron homeostasis and hemoglobin in one comprehensive overview.
Methods: 28 mountaineers (10M/18 F, 44.0±2.6 y., BMI 23.7±0.6kg/m2) were studied. Duodenal biopsies were taken by unsedated nasal endoscopy from each volunteer at 490m in Zurich [ZH] at baseline and 2 [CM2] and 4 [CM4] days after rapid ascent to 4559m to Capanna Regina Margherita in the Alps. Blood samples were drawn in a fasting state at 8 a.m. on day 0 [ZH], 2 [CM2] and 4 [CM4]. RNA was extracted from intestinal biopsy specimens and mRNA expression levels of the divalent metal transporter I (DMT1) was measured by RT-PCR. Iron, ferritin, transferrin, transferrin saturation and CRP were quantified by standard autoanalyzer techniques. Plasma IL-6 and erythropoietin levels were measured using ELISA. All data were correlated to clinical measurements including arterial oxygen saturation (SO2). All data are given as mean±SEM. Differences between ZH, CM2 and CM4 were calculated by a mixed effect linear model.
Results: Arterial SO2 was lower at high altitude (CM2 and CM4) than in Zürich (76±1 and 80±1 vs. 95±1%; p<0.001). Erythropoietin increased under hypoxic conditions (72±6 and 30±3 vs. 6±1 mU/ml; p<0.001) followed by a erythropoietic response indicated by increased intestinal DMT1 expression (1007±282 and 941±249 vs. 137±165% compared to villin; p<0.001) and low serum iron only on CM4 (23±2 and 12±2 vs. 24±1µmol/l, p<0.001). Serum ferritin also declined rapidly (108±7 and 96±6 vs.141±22µg/l, p<0.001). Plasma CRP and IL-6 increased on CM2 and CM4 for CRP and only on CM2 for IL-6 (CRP: 2.9±0.5 and 2.8±0.5 vs. 0.7±0.4mg/l, p<0.001; IL6: 2.7±0.5 and 1.5±0.5 vs. 0.9±0.3ng/l; p<0.001)
Conclusion: This human healthy volunteer study showed for the first time that duodenal iron transport is rapidly upregulated under hypoxemic conditions to compensate increased iron consumption and mobilization of storage iron of enhanced erythropoesis.