Hyperbaric Oxygen Therapy (HBOT) consists of entry into a chamber where oxygen content, and pressure are increased.
HBOT is FDA approved for fourteen health conditions including infections, vision loss, hearing loss, wound healing and anemia, and carries risks of lung collapse(rare), transient vision changes, ear injury, nasal-sinus pain, and oxygen poisoning (1, 3). Some of these risks can be minimized by keeping sessions to less than 2 hours long, and by ensuring the pressure is not increased by more than 3 x normal atmospheric pressure. Mechanisms of action include alterations in relevant transcription factors, improvement in mitochondrial function, and oxidative stress resistance(10).
A retrospective analysis of 162 human stroke patients showed that HBOT improved all areas of memory and motor function that were measured after 40-60 sessions of 90 minutes of 100% oxygen at 2 ATA 5 days per week(3).
A prospective randomized controlled trial evaluated patients between 6 and 36 months after having a stroke and receiving HBOT. The study used 90 minute sessions, 5 days per week for 40 sessions and found improvements in life quality and neurological function compared to the control group(11,10, 1).
In animal studies, HBOT has curbed oxidative stress, produced neurogenesis (growth of new brain cells), decreased apoptosis (cell death), decreased inflammation, and improved cognitive function in traumatic brain injury patients(4, 5, 6, 7, 8).
Pre-clinical studies in humans have presented improvements in cerebral blood flow, traumatic brain injury, mild cognitive impairment, white and grey matter(brain) density, and skin aging(9, 10).
One area of confusion arises from the fact that low oxygen levels can combat hallmarks of aging such as oxidative damage to macromolecules, which occur due to reactive oxygen species produced from oxygen. Therefore some would expect increased oxygen levels to accelerate aging. However, anti-oxidant mechanisms are highly complex and do not linearly correlate with oxygen levels. Very high and low levels of oxygen both have caused oxidative stress in fruit flies(14), while high and low oxygen levels have also been associated with oxidative stress in worms and human cells(15). High and low oxygen levels have also been associated with enhanced oxidative damage protection in roundworms and human cells (16,15).
A study of 11 humans illuminated no increase in measurements of cellular oxidative damage following three 110 minute sessions at 24 hour intervals under increased oxygen concentration and pressure(18). Coincidingly, a pilot interventional study of 10 humans used a single session of HBOT lasting 1 hour and 40 minutes and showed improved levels in markers of oxidative and cellular stress and inflammation(19).
Immune cell telomere length in 14 human subjects were compared to 15 control subjects over 12 months in a study of scuba-divers exposed to hyperbaric oxygen. The results were unclear as not all biomarkers were measured. Telomere length did increase initially, but then rapidly decreased in length(20).
60 daily HBOT sessions were administered to 35 adult humans and magnified significantly shortened telomere length and decreased senescence in immune cells(21).
Researchers need to further investigate adequate duration and technique to determine how to maximize benefits in non-FDA-approved areas.
By: Evan Redmond, Pharm.D.
Resources:
1.https://www.fda.gov/consumers/consumer-updates/hyperbaric-oxygen-therapy-get-facts
2.https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/hyperbaric-oxygen-therapy
3.Hadanny A, Rittblat M, Bitterman M, May-Raz I, Suzin G, Boussi-Gross R, Zemel Y, Bechor Y, Catalogna M, Efrati S. Hyperbaric oxygen therapy improves neurocognitive functions of post-stroke patients - a retrospective analysis. Restor Neurol Neurosci. 2020;38(1):93-107. doi: 10.3233/RNN-190959. PMID: 31985478; PMCID: PMC7081098.
4.Shwe T, Bo-Htay C, Ongnok B, Chunchai T, Jaiwongkam T, Kerdphoo S, Kumfu S, Pratchayasakul W, Pattarasakulchai T, Chattipakorn N, Chattipakorn SC. Hyperbaric oxygen therapy restores cognitive function and hippocampal pathologies in both aging and aging-obese rats. Mech Ageing Dev. 2021 Apr;195:111465. doi: 10.1016/j.mad.2021.111465. Epub 2021 Mar 1. PMID: 33662435.
5. Ahmadi F, Khalatbary AR. A review on the neuroprotective effects of hyperbaric oxygen therapy. Med Gas Res. 2021 Apr-Jun;11(2):72-82. doi: 10.4103/2045-9912.311498. PMID: 33818447; PMCID: PMC8130666.
6. Liu S, Shen G, Deng S, Wang X, Wu Q, Guo A. Hyperbaric oxygen therapy improves cognitive functioning after brain injury. Neural Regen Res. 2013 Dec 15;8(35):3334-43. doi: 10.3969/j.issn.1673-5374.2013.35.008. PMID: 25206655; PMCID: PMC4145948.
7. Cozene B, Sadanandan N, Gonzales-Portillo B, Saft M, Cho J, Park YJ, Borlongan CV. An Extra Breath of Fresh Air: Hyperbaric Oxygenation as a Stroke Therapeutic. Biomolecules. 2020 Sep 4;10(9):1279. doi: 10.3390/biom10091279. PMID: 32899709; PMCID: PMC7563917.
8. Mu J, Krafft PR, Zhang JH. Hyperbaric oxygen therapy promotes neurogenesis: where do we stand? Med Gas Res. 2011 Jun 27;1(1):14. doi: 10.1186/2045-9912-1-14. PMID: 22146131; PMCID: PMC3231808.
9. Hachmo Y, Hadanny A, Mendelovic S, Hillman P, Shapira E, Landau G, Gattegno H, Zrachya A, Daniel-Kotovsky M, Catalogna M, Fishlev G, Lang E, Polak N, Doenyas K, Friedman M, Zemel Y, Bechor Y, Efrati S. The effect of hyperbaric oxygen therapy on the pathophysiology of skin aging: a prospective clinical trial. Aging (Albany NY). 2021 Nov 16;13(22):24500-24510. doi: 10.18632/aging.203701. Epub 2021 Nov 16. PMID: 34784294; PMCID: PMC8660605.
10. Gottfried I, Schottlender N, Ashery U. Hyperbaric Oxygen Treatment-From Mechanisms to Cognitive Improvement. Biomolecules. 2021 Oct 15;11(10):1520. doi: 10.3390/biom11101520. PMID: 34680155; PMCID: PMC8533945.
11. Efrati S, Fishlev G, Bechor Y, Volkov O, Bergan J, Kliakhandler K, Kamiager I, Gal N, Friedman M, Ben-Jacob E, Golan H. Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial. PLoS One. 2013;8(1):e53716. doi: 10.1371/journal.pone.0053716. Epub 2013 Jan 15. PMID: 23335971; PMCID: PMC3546039.
14. Rascón B, Harrison JF. Lifespan and oxidative stress show a non-linear response to atmospheric oxygen in Drosophila. J Exp Biol. 2010 Oct 15;213(Pt 20):3441-8. doi: 10.1242/jeb.044867. PMID: 20889824.
15. Honda Y, Honda S. Oxidative stress and life span determination in the nematode Caenorhabditis elegans. Ann N Y Acad Sci. 2002 Apr;959:466-74. doi: 10.1111/j.1749-6632.2002.tb02117.x. PMID: 11976220.
16. Fu Q, Duan R, Sun Y, Li Q. Hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics. Redox Biol. 2022 Jul;53:102352. doi: 10.1016/j.redox.2022.102352. Epub 2022 May 27. PMID: 35649312; PMCID: PMC9156818.
18. de Wolde SD, Hulskes RH, de Jonge SW, Hollmann MW, van Hulst RA, Weenink RP, Kox M. The Effect of Hyperbaric Oxygen Therapy on Markers of Oxidative Stress and the Immune Response in Healthy Volunteers. Front Physiol. 2022 Jan 31;13:826163. doi: 10.3389/fphys.2022.826163. PMID: 35173631; PMCID: PMC8843016.
19. Chang JS, Chang E, Lee Y, Cha YS, Cha SK, Cho WG, Jeong Y, Kim H, Park KS. Hyperbaric Oxygen Exposure Attenuates Circulating Stress Biomarkers: A Pilot Interventional Study. Int J Environ Res Public Health. 2020 Oct 27;17(21):7853. doi: 10.3390/ijerph17217853. PMID: 33120884; PMCID: PMC7663415.
20. Shlush LI, Skorecki KL, Itzkovitz S, Yehezkel S, Segev Y, Shachar H, Berkovitz R, Adir Y, Vulto I, Lansdorp PM, Selig S. Telomere elongation followed by telomere length reduction, in leukocytes from divers exposed to intense oxidative stress--implications for tissue and organismal aging. Mech Ageing Dev. 2011 Mar;132(3):123-30. doi: 10.1016/j.mad.2011.01.005. Epub 2011 Feb 12. PMID: 21320523.
21. Hachmo Y, Hadanny A, Abu Hamed R, Daniel-Kotovsky M, Catalogna M, Fishlev G, Lang E, Polak N, Doenyas K, Friedman M, Zemel Y, Bechor Y, Efrati S. Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. Aging (Albany NY). 2020 Nov 18;12(22):22445-22456. doi: 10.18632/aging.202188. Epub 2020 Nov 18. PMID: 33206062; PMCID: PMC7746357.
22. Fu Q, Duan R, Sun Y, Li Q. Hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics. Redox Biol. 2022 Jul;53:102352. doi: 10.1016/j.redox.2022.102352. Epub 2022 May 27. PMID: 35649312; PMCID: PMC9156818. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156818/
