Effects of simulated microgravity on human hematological and anemia-related biomarkers: a systematic review and meta-analysis

Abstract Background Space anemia has been observed in astronauts after spaceflights for a long time, but its exact mechanism remains unclear. Because of the practical and ethical challenges of performing human studies in space, researchers use ground-based analogs to study the hematological changes that occur upon exposure to microgravity. Understanding these changes is important for protecting astronauts during long spaceflights and for guiding medical treatment on Earth in cases of prolonged inactivity or bed rest. Methods The literature search was done in April 2025 in PubMed, Web of Science, Scopus, and Cochrane. The inclusion criteria are randomized or non-randomized controlled trials and experimental repeated-measures studies that enrolled humans exposed to simulated microgravity for at least 24 h. This study followed PRISMA (2020) guidelines and was registered in PROSPERO under CRD420251104161. Data was analyzed by Comprehensive Meta-Analysis software. Results Ten studies, involving 152 participants, met the inclusion criteria. During exposure, the first effect was a decreased plasma volume, leading to hemoconcentration. Erythropoietin concentration decreased, while parameters dependent on plasma volume, such as hemoglobin, hematocrit, and RBC count, falsely increased. Total hemoglobin mass and red cell volume showed a marked decrease, suggesting suppressed erythropoiesis. Iron status markers increased significantly, while classic hemolysis markers did not confirm increased hemolysis. Post-reambulation, erythropoietin rebounded, while the true decreases in hemoglobin, hematocrit, and RBC count were revealed as hemoconcentration resolved. Conclusion Simulated microgravity induces hemoconcentration, erythropoietin suppression, and altered iron metabolism. Further investigation is needed to clarify the role of hemolysis and to develop efficient countermeasures.