Efficacy of donepezil plus hydrogen–oxygen mixture inhalation for treatment of patients with Alzheimer disease: A retrospective study
Dan Z, Li H, Xie J. · Medicine. 2023;102(30):e34382.
Study at a glance
Human
273 patients with mild-to-moderate Alzheimer disease treated between March 2018 and March 2022.
Donepezil 5 mg daily plus H₂/O₂ inhalation once daily, six days each week for four weeks. · Generator output was 3 L/min; direct calculation gives approximately 2,000 mL/min H₂ and 1,000 mL/min O₂. Duration of each daily inhalation session was not reported.
Four weeks of treatment with three-month video/telephone or outpatient follow-up described; per-session inhalation duration was not stated.
Four-week cognitive, daily-living and P300 comparisons favored the combined-treatment group. Both groups improved on several measures. Baseline scale scores did not differ significantly. The report did not establish whether improvements persisted at the described three-month follow-up.
Retrospective nonrandomized co-intervention study with no H₂-only arm, possible selection/confounding and treatment-adherence bias, scale-led outcomes, unreported inhalation-session duration and unclear three-month outcome reporting. Hospital support funded the study; authors declared no conflicts and the commercial generator was identified but no material-support statement was provided.
What kind of evidence is this?
Human
Single-hospital retrospective comparative study
Other neurological conditions
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
273 patients with mild-to-moderate Alzheimer disease treated between March 2018 and March 2022.
273 records: donepezil plus H₂/O₂ n=138 and donepezil alone n=135.
Four weeks of treatment with three-month video/telephone or outpatient follow-up described; per-session inhalation duration was not stated.
Donepezil 5 mg daily plus H₂/O₂ inhalation once daily, six days each week for four weeks.
Brown's gas / oxyhydrogen generated as 66.67% H₂ and 33.33% O₂.
Generator output was 3 L/min; direct calculation gives approximately 2,000 mL/min H₂ and 1,000 mL/min O₂. Duration of each daily inhalation session was not reported.
Approximately 2,000 mL/min.
Approximately 1,000 mL/min.
Donepezil 5 mg daily without H₂/O₂; treatment was not randomized.
Outcomes and reported result
MMSE, MoCA, ADAS-Cog, activities of daily living and P300 event-related-potential latency/amplitude.
Four-week cognitive, daily-living and P300 comparisons favored the combined-treatment group. Both groups improved on several measures. Baseline scale scores did not differ significantly. The report did not establish whether improvements persisted at the described three-month follow-up.
The complete free PMC article and tables were checked for retrospective allocation, exact generator output/composition, missing session duration, all cognitive and P300 outcomes, follow-up description, funding and conflicts.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Retrospective nonrandomized co-intervention study with no H₂-only arm, possible selection/confounding and treatment-adherence bias, scale-led outcomes, unreported inhalation-session duration and unclear three-month outcome reporting. Hospital support funded the study; authors declared no conflicts and the commercial generator was identified but no material-support statement was provided.
Mild-to-moderate Alzheimer disease treated with donepezil in one hospital; it does not establish independent H₂ efficacy or disease modification.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 37505148 · DOI: 10.1097/MD.0000000000034382
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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