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Abstract
BACKGROUND: Beneficial effects of breathing at 
< 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with 
as low as 0.11 in 5 healthy volunteers.
METHODS: All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from 
of 0.16 on the first day to 
of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' 
, heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments.
RESULTS: Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased 
and increased heart rate. At 
of 0.14, the mean 
was 92%; at 
of 0.13, the mean 
was 93%; at 
of 0.12, the mean 
was 88%; at 
of 0.11, the mean 
was 85%; and, finally, at an 
of 0.21, the mean 
was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension.
CONCLUSIONS: Results of the current physiologic study suggests that, within a hospital setting, delivering 
as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested.
Footnotes
- Correspondence: Lorenzo Berra MD, Department of Anesthesia, Critical Care and Pain Medicine, 55 Fruit Street Boston, MA 02114. E-mail: lberra{at}mgh.harvard.edu
(ClinicalTrials.gov registration NCT02860975.)
Dr Berra and Mr Medeiros contributed equally.
Dr Mootha is listed as an inventor on patent applications filed by Massachusetts General Hospital on the therapeutic uses of hypoxia. Dr Berra is listed as the inventor on patent applications filed by Massachusetts General Hospital on the therapeutic uses of inhaled nitric oxide.
The study was supported by the J Willard & Alice S Marriott Foundation and departmental funds at the Massachusetts General Hospital.
Supplementary material related to this paper is available at http://www.rcjournal.com.
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