Kinetics of Blood Volume and Hemoglobin Mass Adaptation in Sea-Level Newcomers Relocating to Moderate Altitude: A Six-Month Prospective Study

Background/Objectives: The kinetics of blood volume and hemoglobin mass (Hbmass) adaptation in newcomers to moderate altitude and the time required to reach the hematological phenotype of long-term residents remain poorly defined. We aimed to characterize this trajectory over six months and to compare newcomers with established altitude residents. Methods: Thirty-seven healthy male sea-level newcomers were prospectively followed at baseline (within 48 h of arrival), two months, and six months after relocation to Abha, Saudi Arabia (2250 m). Hbmass, blood volume (BV), plasma volume (PV), and red blood cell volume (RBCV) were measured by CO rebreathing; lean body mass (LBM) was assessed by DXA. Six-month values were compared with 107 long-term male altitude residents. Linear mixed-effects models with Holm–Bonferroni correction were used. Results: Adaptation followed a biphasic trajectory. At two months, RBCV and Hbmass rose significantly from baseline (RBCV + 186 mL, Hbmass + 65 g; both p ≤ 0.005), confirmed by LBM-adjusted analysis. These gains partially regressed by six months, after which no volume parameter differed significantly from baseline. Hemoglobin (Hb) and hematocrit (Hct) remained persistently elevated (+6 g/L, +1.9%; both p < 0.001) due to sustained PV contraction. Compared with long-term residents, six-month newcomers had significantly lower LBM-adjusted Hbmass (15.7 vs. 18.0 g/kg), RBCV (48.0 vs. 54.2 mL/kg), and BV (98.9 vs. 109.8 mL/kg; all p < 0.001), yet Hb and Hct were not significantly different. Conclusions: Moderate altitude acclimatization follows a transient two-month erythropoietic increase, then partial regression. Six months is insufficient to attain the oxygen-carrying capacity of long-term residents’ deficit entirely masked by Hb and Hct. Direct Hbmass measurement normalized to LBM is required for accurate assessment of altitude adaptation.