AUTHOR=MacLaughlin Kent J. , Barton Gregory P. , Braun Rudolf K. , MacLaughlin Julia E. , Lamers Jacob J. , Marcou Matthew D. , Eldridge Marlowe W. TITLE=Hyperbaric air mobilizes stem cells in humans; a new perspective on the hormetic dose curve JOURNAL=Frontiers in Neurology VOLUME=Volume 14 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1192793 DOI=10.3389/fneur.2023.1192793 ISSN=1664-2295 ABSTRACT=Hyperbaric air (HBA) was first used pharmaceutically in 1662 to treat lung disease followed by extensive use in Europe and North America throughout the 19th century to treat pulmonary and neurological disorders. HBA reached its zenith in the early 20th century when cyanotic, moribund “Spanish flu pandemic” patients turned normal color and regained consciousness within minutes after HBA treatment. Since that time the 78% Nitrogen fraction in HBA has been wholly displaced by 100% oxygen to create the modern hyperbaric oxygen therapy (HBOT), a powerful treatment FDA approved for multiple indications. Current belief purports oxygen as the active element mobilizing stem progenitor cells (SPCs) in HBOT, but hyperbaric air, which increases tensions of both oxygen and nitrogen, has been untested until now. In this study we test HBA for SPC mobilization, cytokine and chemokine expression, and complete blood count. Ten 34–35-year-old healthy volunteers were exposed to 1.27ATA (4psig/965mmHg) room air for 90 minutes, M-F, for 10 exposures over 2-weeks. Venous blood samples were taken: 1) prior to the first exposure (served as the control for each subject), 2) directly after the first exposure (to measure the acute effect), 3) immediately prior to the ninth exposure (to measure the chronic effect), and 4) three days after the completion of tenth/final treatment (to assess durability). SPCs were gated by blinded scientists using Flow Cytometry. SPCs (CD45dim/CD34+/CD133-) were mobilized by nearly two-fold following 9 exposures (p = .02) increasing to 3-fold 72-hours post completion of the final (10th) exposure (p=.008) suggesting durability. This research demonstrates that SPCs are mobilized, and cytokines are modulated by hyperbaric air. HBA likely is a therapeutic treatment. Previously published research using HBA placebos should be re-evaluated. Our findings that hyperbaric air mobilizes stem progenitor cells support further investigation into hyperbaric air as a therapy/medication.