Sociodemographic and Lifestyle Determinants of HIF-1α Response to Blood Donation and Hematopoietic Factors: Epidemiological and Public Health Perspectives from Voluntary Donors

<b>Background/Objectives:</b> Blood donation is essential to health systems and represents a valuable epidemiological model for studying physiological adaptation to controlled blood loss. Regular blood donors constitute a distinct, health-screened population whose biological responses offer unique insight into mechanisms of resilience and key determinants of population health. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key regulator of erythropoiesis and cellular response to hypoxia, and its modulation following blood donation may inform donor safety and the sustainability of blood donation programs. This study aimed to characterize the sociodemographic, lifestyle, and anthropometric profiles of blood donors in relation to hematopoietic biomarkers (vitamin B12 and folic acid) and to evaluate changes in serum HIF-1α concentration after donation, emphasizing the public health relevance of voluntary blood donation. <b>Methods:</b> A cross-sectional study was conducted among 324 voluntary blood donors (159 regular and 165 occasional). Serum HIF-1α was measured before and 30 min after donation, together with vitamin B12 and folic acid levels. Sociodemographic and lifestyle characteristics (physical activity, smoking, dietary habits) were collected through standardized questionnaires (EHIS-3, FFQ), and anthropometric parameters were assessed. <b>Results:</b> Regular donors were older and predominantly male, with comparable socioeconomic indicators between groups. Both regular and occasional donors showed favorable lifestyle profiles, including low smoking prevalence and moderate physical activity. Skinfold thickness was significantly greater in regular donors (<i>p</i> < 0.001). The main biological finding was a robust post-donation increase in HIF-1α concentrations (≈80%, <i>p</i> < 0.001), independent of donation frequency or lifestyle. No significant associations were found between lifestyle factors and vitamin B12 or folate levels. <b>Conclusions:</b> Blood donation induces a rapid elevation in HIF-1α, reflecting activation of hypoxia-responsive pathways and short-term hematopoietic adaptation. Beyond its biomedical relevance, voluntary blood donation represents a meaningful epidemiological and public health model for studying physiological resilience and the health benefits of altruistic behavior. These findings underscore the importance of donor surveillance and motivation as components of broader preventive health and health equity strategies.