Erythropoiesis, Hypoxia, Iron Metabolism Disorders
Conditions
Brief summary
This study investigates how training under conditions of reduced oxygen (intermittent hypoxia) affects the body's ability to produce red blood cells and manage iron levels, compared to training under normal oxygen conditions. Red blood cells are essential for transporting oxygen throughout the body, and their production depends on having enough available iron. Thirty-two physically trained participants completed a 3-week training program, either in low-oxygen conditions or in normal oxygen conditions. All participants followed the same diet and received daily supplements of iron and vitamins to ensure adequate nutritional support. The main hypothesis of this study is that training in low-oxygen conditions stimulates the production of red blood cells more strongly than training in normal oxygen conditions, and that this increased production requires the body to use stored iron, potentially lowering iron reserves. Results showed that participants training in low-oxygen conditions experienced a greater increase in red blood cells and related markers compared to those training in normal conditions. At the same time, their stored iron levels decreased, suggesting that the body was using its iron reserves to support the increased production of red blood cells. In contrast, participants training in normal oxygen conditions showed smaller changes and maintained or slightly increased their iron stores. These findings suggest that low-oxygen training can enhance the body's capacity to produce red blood cells but may also reduce iron reserves. This highlights the importance of monitoring iron levels during such training programs, especially in athletes or individuals with conditions related to low oxygen availability, such as anemia. Overall, this study aims to improve understanding of how oxygen availability influences blood health and may help guide future strategies that combine hypoxia training and iron supplementation to support performance and treat certain medical conditions.
Interventions
OTHERControl group (CG)
3-week normoxic training program (14 sessions, 90 min/session) with identical exercise structure to the hypoxia group (strength-resistance circuit + cycling intervals), performed at sea-level oxygen conditions inside the same tent to ensure blinding. Frequency: 4-5 sessions/week. All participants received daily oral supplementation: iron 60 mg (ferrous sulfate + ferrous fumarate) + vitamin C 200 mg + folic acid 200 µg + vitamin B12 6 µg. Diet provided \~55 kcal/kg/day (carbohydrates 7-8 g/kg, protein 1.6-2 g/kg, fat 1-1.5 g/kg).
OTHERHypoxia group (HG): trained at simulated altitudes between 4,450 and 5,850 m
3-week normobaric intermittent hypoxia training program (14 sessions, 90 min/session: 60 min active + 30 min passive hypoxia) at simulated altitudes of 4,450-5,850 m (SaO₂ \~80%). Training combined strength-resistance circuit (30 min) and high-intensity cycling intervals (30 min). Frequency: 4-5 sessions/week. All participants received daily oral supplementation: iron 60 mg (ferrous sulfate + ferrous fumarate) + vitamin C 200 mg + folic acid 200 µg + vitamin B12 6 µg. Diet provided \~55 kcal/kg/day (carbohydrates 7-8 g/kg, protein 1.6-2 g/kg, fat 1-1.5 g/kg).
Sponsors
Néstor Vicente-Salar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Participants were assigned to one of two parallel groups: a hypoxia training group (HG) or a normoxic control group (CG). Allocation followed an alternating sequence as participants enrolled. Both groups completed the same structured 3-week training program (4-5 sessions/week; 90 min/session), consisting of combined strength-resistance and aerobic exercise performed inside an environmental tent. The HG trained under normobaric intermittent hypoxia (simulated altitude 4,450-5,850 m), while the CG trained under normoxic conditions, with participants blinded to the environmental setting. Each session included 60 min of active training and 30 min of passive exposure. Physiological variables (oxygen saturation, heart rate, lactate, workload relative to VO₂max) were continuously monitored.
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Male sex * Adult age (≥18 years) * Federated mountain sports practitioner (alpinist, trail runner, ski mountaineer, or endurance runner) * Normal hemoglobin levels at screening (≥13 g/dL) * Residence at elevations below 700 m * Provision of written informed consent prior to enrollment * Agreement to comply with the principles of the Declaration of Helsinki (WMA, 2024 revision)
Exclusion criteria
* Stay at altitudes above 2,000 m within the previous 2 months prior to enrollment * Any form of anemia at screening (hemoglobin \<12-13 g/dL) * Sports-related pseudoanemia * Presence of cardiovascular or respiratory pathologies, as determined by the medically supervised VO₂max exercise test * Female sex
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin concentration | Baseline and 3 weeks (end of intervention) | Venous blood hemoglobin concentration (g/dL) measured at baseline and 3 days after completion of the 3-week intervention. Blood samples collected in the morning (08:00-10:00 h) after overnight fast (≥8 h) and 10 min of seated rest, analyzed by automated laboratory analyzer following CLSI standards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Red blood cell count | Baseline and 3 weeks (end of intervention) | Venous blood erythrocyte concentration (×10⁶ cells/mm³) measured at baseline and 3 days after completion of the 3-week intervention. Blood samples collected in the morning (08:00-10:00 h) after overnight fast (≥8 h) and 10 min of seated rest, analyzed by automated laboratory analyzer following CLSI standards. |
| Hematocrit | Baseline and 3 weeks (end of intervention) | Percentage of red blood cells in total blood volume (%) measured at baseline and 3 days after completion of the 3-week intervention. Blood samples collected under identical conditions to primary outcome measure. |
| Serum ferritin | Baseline and 3 weeks (end of intervention) | Serum ferritin concentration (ng/mL) as an indicator of iron storage status, measured at baseline and 3 days after completion of the 3-week intervention. Obtained from serum separator tubes analyzed by automated laboratory analyzer following CLSI standards. |
| Reticulocyte count | Baseline and 3 weeks (end of intervention) | Percentage of reticulocytes (immature red blood cells) in peripheral blood (%), used as an indirect indicator of erythropoietic activity. Measured at baseline and 3 days after completion of the 3-week intervention under identical sampling conditions. |
Countries
Spain
Contacts
STUDY_DIRECTOREnrique Roche, Full Professor
University Miguel Hernández of Elche
Outcome results
None listed