To compare the effects of IV iron versus placebo (saline) injection on arterial oxygen saturation, submaximal exercise responses, and 2-mile treadmill time-trial performance during acute exposure to hypobaric hypoxia (430 mmHg, simulating ~4800m) assessed 1 and 14 days after treatment.

Primary Hypothesis 1: IV iron treatment will improve arterial oxygen saturation at rest and during exercise in acute hypobaric hypoxia and this effect will persist for 2 weeks

Primary Hypothesis 2) IV iron treatment will improve 2-mile treadmill time trial performance in acute hypobaric hypoxia and this effect will persist for 2 weeks

This study will use a double-blind randomized study design in which one group will receive iron (n = 12; Injectafer, 15 mg/kg up to 1000 mg) and the other a placebo (n = 12; saline). Twenty-four participants will complete seven study visits: Visit 1: Orientation visit consisting of dual-energy X-ray absorptiometry scan (DEXA), pulmonary function test, assessment of peak aerobic capacity (VO2peak); Visits 2-3: familiarization consisting of exercise battery (20 minutes of walking followed by 2 mile treadmill time trial); Visits 4, 6-7: high altitude trial (4,800 m) in which skin blood flow during rest will be measured, ventilation at sea level and altitude will be assessed, collection of sea level and altitude arterialized capillary and venous blood will be collected, and the exercise battery. Visit 5: participants will receive the iron or placebo.

Inclusion Criteria:

• Man or woman, age 18-40 years

  • BMI 18.5-30 kg/m2
  • In good health as determined by the Office of Medical Support & Oversight (OMSO) General Medical Clearance
  • Passed his/her most recent Army Combat Fitness Test (ACFT) (Military Volunteers Only) or exercises at least 2 times per week and able to complete two mile run in ≤ 21 minutes (Civilian Volunteers)
  • Willing to not exercise, or drink alcoholic/caffeinated beverages 24 hours prior to each testing session
  • Willing to not perform any strenuous exercise 36 hours prior to each testing session

Exclusion Criteria:

• Women who are pregnant or planning to become pregnant during the study

  • Taking prescription medication, or over-the-counter medications other than contraceptives, unless approved by OMSO & PI
  • Taking dietary supplements unless approved by OMSO & PI
  • Born at altitudes greater than 2,100 m (7,000 ft)
  • Living in areas that are more than 1,200 m (4,000 ft) or have traveled to areas that are more than 1,200 m for five days or more within the last 2 months
  • Prior diagnosis of High Altitude Pulmonary Edema (HAPE) or High Altitude Cerebral Edema (HACE)
  • Musculoskeletal injuries that compromise the ability to walk/run on a treadmill
  • Presence of abnormal blood chemicals (hemoglobin S or Sickle Cell Trait)
  • Hemoglobin concentration: men: Hb <13.5 g/dL or Hb >17.7 g/dL; women Hb <12.5 g/dL or Hb >15.9 g/dL
  • Ferritin < 50 ng/mL or greater than 150 ng/mL
  • Any history of malignancy
  • Personal or family history of blood clots
  • History of thromboembolic disease, hypertension, and known risk factors of cardiovascular disease
  • Blood donation within 8 weeks of beginning the study
  • History of seizures
  • History of inflammatory bowel disease
  • Any recent (within 4-6 weeks) and or expected history of prolonged periods of immobility or limited activity (including recent or upcoming surgery)
  • Abnormal PT/PTT test or problems with blood clotting
  • Any nicotine or recreational drug use (unless quit > 1 month prior to study orientation)
  • Presence of respiratory tract infections (< 1 month prior)
  • Experience recent cold, coughs, or sinus infections (< 2 weeks prior)
  • Allergy to skin adhesive
  • Evidence of apnea or sleeping disorder
  • Present condition of alcoholism, use of anabolic steroids, other substance abuse issues
  • Body mass <50 kg (110.5 lbs)
  • History of hyperparathyroidism
  • History of vitamin D deficiency
  • History of systemic inflammatory disease (rheumatoid arthritis, lupus erythematosus)
  • Any drug allergies
  • History of hypersensitivity reaction
  • History of asthma
  • History of kidney or liver disease
  • Any previous intravenous iron injection

Participants and Investigator will be blinded to who receives iron or placebo. A investigator not participating in data collection is responsible for randomly assigning participants to the intervention. The medical care providers will be unblinded to intervention assignment.