Fatigue disappearance in hemodialysis patients by dual approach with hydrogen gas inhalation and hydrogen-enriched dialysate: two case reports
Nakazawa R, Nagami S, Nozaki H, Yataka M, Akiyama K, Uchino T, Azuma N. · Medical Gas Research. 2025;15(1):59–61.
What kind of evidence is this?
Human
Two-patient uncontrolled before/after case report with treatment withdrawal observations
Kidney and urinary health
Inhaled H₂
Not reported in this record.
Not reported in this record.
Methods at a glance
Two men aged 64 and 53 years undergoing long-term hemodialysis/hemodiafiltration with severe post-dialysis fatigue.
Two patients treated at one clinic; there was no randomized or concurrent control group.
Four to five hours per dialysis session, three sessions weekly, for three months.
Existing electrolyzed-water online hemodiafiltration using H₂-enriched dialysate plus pure H₂ by nasal cannula throughout dialysis, three times weekly for three months.
Two H₂-only routes: dissolved H₂ in dialysate and nasal-cannula H₂ gas — not Brown's gas; no O₂ was generated or supplied with the H₂ stream.
Dialysate averaged 300 ppb dissolved H₂. The generator supplied 99.99% H₂ at 250 mL/min; the article describes an estimated inhaled concentration of 2.5%.
250 mL/min H₂ from the nasal-cannula generator for each 4–5-hour dialysis session.
No supplemental O₂ was co-delivered; ambient-air breathing/entrainment was not quantified.
Within-person periods of conventional hemodiafiltration and electrolyzed-water hemodiafiltration without gas inhalation; treatment order was not randomized or blinded.
Outcomes and reported result
SONG-HD fatigue, EQ visual-analogue health score, serum citrullinated histone H3 and selected oxidative/endothelial biomarkers.
Both patients' reported fatigue and EQ-VAS improved during combined therapy and worsened again after return to conventional dialysis; several biomarkers changed in the reported favorable direction. The design cannot separate H₂ inhalation from H₂ dialysate, order, expectation or other time effects.
The complete free PMC report and table were checked for both cases, dual-route dosing, exact H₂ gas flow/purity, patient-reported and biomarker outcomes, reversal observation, limitations and disclosure gaps.
A reported association, difference or mechanism is not automatically a clinical benefit. Null findings, outcome type, study design and precision all matter.
Cautions and applicability
Only two unblinded cases, subjective outcomes, combined intervention, no concurrent control and extensive previous exposure to H₂ dialysate. The report names commercial dialysate and H₂-generator products; no explicit funding or conflict statement was identified, so their absence is not inferred.
Hypothesis-generating observations in two long-term dialysis patients; they do not establish efficacy, comparative safety or optimal dosing.
Not reported in this record.
Not reported in this record.
Not reported in this record.
No single-study GRADE certainty rating is assigned. Certainty is assessed by important outcome across a complete eligible evidence set, not by attaching a final grade to one source.
Sources and record status
PMID: 39436179 · DOI: 10.4103/mgr.MEDGASRES-D-24-00024
Free full article in PubMed Central.
Complete PMC article and PubMed metadata; full-text extraction checked 9 August 2026.
2026-08-10