Iron Metabolism Regulation in Females and Males Exposed to Simulated Microgravity: results from the Randomized Trial AGBRESA

Abstract

Background: Iron metabolism imbalance could contribute to physical deconditioning experienced by astronauts due to its essential role in energy metabolism, cellular respiration, and oxygen transport. Objectives: In this clinical exploratory study, we wanted to determine whether artificial gravity (AG) training modulated iron metabolism, red blood cell indices, and body lean mass in male and female healthy participants exposed to head-down tilt (HDT) bed rest, the reference ground-based model of microgravity. Methods: We recruited 8 female and 16 male healthy participants who were all exposed to HDT bed rest for 60 days. In addition, they were assigned to three experimental groups (n = 8/each): controls, continuous AG training in a short-arm centrifuge (1×30 min/day), and intermittent AG training (6 × 5 min/day). Results: The iron metabolism responses to simulated microgravity of AG training groups do not significantly differ from the responses of controls. Independently from AG, we found that both serum iron (+31.3%, P = 0.027) and transferrin saturation levels (+28.4%, P = 0.009) increased in males after 6 days of HDT bed rest, as well as serum hepcidin levels (+36.9% P = 0.005). The increase of transferrin saturation levels persisted after 57 days of HDT bed rest (+13.5%, P = 0.026), suggesting that long-term exposure to microgravity sustainably increases serum iron availability in males, and consequently the risk of iron excess or misdistribution. In females, 6 and 57 days of HDT bed rest did not significantly change serum iron, transferrin saturation, and hepcidin levels. Conclusions: The data from this exploratory study suggest that 1) AG training does not influence the iron metabolism responses to microgravity; 2) iron metabolism parameters, especially iron availability for cells, are significantly increased in males, but not in females, exposed to long-term simulated microgravity. Due to the small sample size of females, we nevertheless must be cautious before concluding that iron metabolism could differently respond to microgravity in females. Clinical trial registry number: DRKS00015677.