Safety of prolonged inhalation of hydrogen gas in air in healthy adults
Cole AR, Sperotto F, DiNardo JA, Carlisle S, Rivkin MJ, Sleeper LA, Kheir JN. · Critical Care Explorations. 2021;3(10):e0543.
Study at a glance
Human
Healthy adults aged 18–30 years admitted for directly observed high-flow nasal-cannula exposure.
Premixed 2.4% H₂ in medical air delivered continuously by heated, humidified high-flow nasal cannula at 15 L/min after a four-hour medical-air acclimatization period. · Certified premix containing 2.4% H₂ in 21% O₂, balance nitrogen; total delivered flow 15 L/min.
Continuous exposure for 24, 48 or 72 hours, followed by testing and telephone follow-up one day and three to five days later.
No clinically significant adverse event or organ-injury signal was observed. FEV1, FVC, FEV1/FVC, neurologic scores and most laboratory measures were unchanged; small heart-rate, peak-flow, hemoglobin, hematocrit, platelet and chloride changes were judged clinically insignificant.
Only eight young healthy adults, single arm, no blinding and insufficient power to detect uncommon harms or establish safety in patients. Serum H₂ was not measured. The Pappendick Family award, Harvard Catalyst, NIH/NCATS and Harvard-affiliated institutions supported the work; authors disclosed no conflicts.
What kind of evidence is this?
Human
Prospective single-arm sequential-duration inpatient safety study
Other molecular hydrogen research
Inhaled H₂
Information not yet classified
Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.
Methods
Healthy adults aged 18–30 years admitted for directly observed high-flow nasal-cannula exposure.
Eight participants completed exposure: n=2 for 24 hours, n=2 for 48 hours and n=4 for 72 hours; four were women and four men.
Continuous exposure for 24, 48 or 72 hours, followed by testing and telephone follow-up one day and three to five days later.
Premixed 2.4% H₂ in medical air delivered continuously by heated, humidified high-flow nasal cannula at 15 L/min after a four-hour medical-air acclimatization period.
H₂ alone as the study gas diluted in medical air — not Brown's gas or oxyhydrogen.
Certified premix containing 2.4% H₂ in 21% O₂, balance nitrogen; total delivered flow 15 L/min.
360 mL/min H₂, calculated directly from the reported 15,000 mL/min total flow × 2.4% H₂.
3,150 mL/min O₂, calculated directly from 15,000 mL/min × the reported 21% O₂; O₂ was carrier medical air, not a Brown's-gas co-product.
No concurrent control; participants had baseline testing and a four-hour 15 L/min medical-air period without H₂.
Outcomes and reported result
Symptoms and adverse events, vital signs, spirometry, ECG/telemetry, neurologic examination, Mini-Mental State Examination and hematologic, renal, hepatic, pancreatic and cardiac laboratory tests.
No clinically significant adverse event or organ-injury signal was observed. FEV1, FVC, FEV1/FVC, neurologic scores and most laboratory measures were unchanged; small heart-rate, peak-flow, hemoglobin, hematocrit, platelet and chloride changes were judged clinically insignificant.
The complete free PMC article, protocol, tables, figures and disclosures were checked for gas composition and flow, duration cohorts, positive and null safety findings, limitations, funding and conflicts.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Only eight young healthy adults, single arm, no blinding and insufficient power to detect uncommon harms or establish safety in patients. Serum H₂ was not measured. The Pappendick Family award, Harvard Catalyst, NIH/NCATS and Harvard-affiliated institutions supported the work; authors disclosed no conflicts.
Short phase-one-style tolerability evidence in healthy young adults at this exact mixture and high-flow protocol; it does not establish clinical benefit or safety in ill or older populations.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 34651133 · DOI: 10.1097/CCE.0000000000000543
Free full article in PubMed Central.
Complete PMC article and PubMed metadata; full-text extraction checked 9 August 2026.
10 August 2026
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