High-Altitude Acclimatization Suppresses Hepcidin Expression During Severe Energy Deficit

Hennigar, Stephen R., Claire E. Berryman, Alyssa M. Kelley, Bradley J. Anderson, Andrew J. Young, James P. McClung, and Stefan M. Pasiakos. High-altitude acclimatization suppresses hepcidin expression during severe energy deficit. High Alt Med Biol. 21:232-236, 2020. The erythropoietic cells in the bone marrow require iron to synthesize heme for incorporation into hemoglobin. Exposure to hypoxic conditions, such as extended sojourns to high altitude (HA), results in increased erythropoiesis and an increased physiological requirement for iron. In addition to increasing iron requirements, hypoxic conditions suppress appetite and often lead to decreased energy intake. The objective of this study was to determine the combined effects of severe energy deficit and hypoxia on hepcidin and measures of iron status in lowlanders sojourning to HA. Iron status indicators and hepcidin were determined in 17 healthy male volunteers (mean ± standard deviation, age 23 ± 6 years, body mass index 27 ± 4 kg/m²) fed a controlled diet (12 ± 1.2 mg iron/day) during a 20-day sojourn to 4300 m above sea level. Chronic exposure to HA during severe energy deficit increased hematocrit by 12% (p < 0.01) and decreased serum hepcidin by 37% (p < 0.01) compared with baseline. Ferritin declined by 18% (p = 0.02) and transferrin saturation and soluble transferrin receptor increased by 55% and 83%, respectively (p < 0.01 for both) compared with baseline. HA acclimatization suppresses hepcidin expression to increase iron availability during severe energy deficit. Registered at ClinicalTrials.gov as NCT02731066.