Hydrogen gas activates coenzyme Q10 to restore exhausted CD8+ T cells, especially PD-1+Tim3+terminal CD8+ T cells, leading to better nivolumab outcomes in patients with lung cancer
Akagi J, Baba H. · Oncology Letters. 2020;20(5):258.
Study at a glance
Human
People with stage IV lung carcinoma treated with nivolumab between July 2016 and July 2018.
Nivolumab 1 mg/kg every two weeks plus gas inhalation, usually for 3 hours/day; a few participants inhaled for up to 10 hours/day. · Device output was 1.67 L/min; gas chromatography measured 680,000 ppm H₂ (68%) and 320,000 ppm O₂ (32%).
Daily inhalation during follow-up; the article describes follow-up/exposure extending as long as 60 months.
Median overall survival was reported as 28 months with nivolumab plus gas and 9 months with nivolumab alone. Biomarker analyses linked lower PD-1+Tim-3+ terminal CD8+ T-cell proportions and higher coenzyme Q10 with survival, but not all inhalation participants showed the proposed biomarker direction. These associations do not establish that the gas caused the survival difference.
This was not randomized. The authors state that, after apparent early benefit, investigators preferentially selected combined treatment, creating serious selection and calendar-time bias. Groups were very unequal, biomarker subsets were smaller, and responder/biomarker analyses were exploratory. The safety sentence refers to 56 inhaling patients although only 42 were assigned gas; the inconsistency is unresolved. The article states no funding and the authors declared no competing interests.
What kind of evidence is this?
Human
Prospective nonrandomized cohort with biomarker analyses
Cancer 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
People with stage IV lung carcinoma treated with nivolumab between July 2016 and July 2018.
56 participants: 42 received nivolumab plus gas inhalation and 14 received nivolumab alone. Biomarker analyses used smaller subsets.
Daily inhalation during follow-up; the article describes follow-up/exposure extending as long as 60 months.
Nivolumab 1 mg/kg every two weeks plus gas inhalation, usually for 3 hours/day; a few participants inhaled for up to 10 hours/day.
Oxyhydrogen/Brown's-gas-type mixture containing H₂ and O₂ — not H₂ alone.
Device output was 1.67 L/min; gas chromatography measured 680,000 ppm H₂ (68%) and 320,000 ppm O₂ (32%).
Approximately 1,136 mL/min H₂, calculated as 68% of the reported 1,670 mL/min total output.
Approximately 534 mL/min O₂, calculated as 32% of the reported 1,670 mL/min total output.
Nivolumab without gas inhalation.
Outcomes and reported result
Overall survival, progression-free survival, peripheral CD8+ T-cell exhaustion markers and coenzyme Q10.
Median overall survival was reported as 28 months with nivolumab plus gas and 9 months with nivolumab alone. Biomarker analyses linked lower PD-1+Tim-3+ terminal CD8+ T-cell proportions and higher coenzyme Q10 with survival, but not all inhalation participants showed the proposed biomarker direction. These associations do not establish that the gas caused the survival difference.
The complete PubMed Central article, gas composition and output, treatment allocation, survival analyses, biomarker denominators, safety wording, funding and conflict statements were checked.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
This was not randomized. The authors state that, after apparent early benefit, investigators preferentially selected combined treatment, creating serious selection and calendar-time bias. Groups were very unequal, biomarker subsets were smaller, and responder/biomarker analyses were exploratory. The safety sentence refers to 56 inhaling patients although only 42 were assigned gas; the inconsistency is unresolved. The article states no funding and the authors declared no competing interests.
Stage IV lung carcinoma treated with nivolumab in this highly selected observational cohort; not evidence that oxyhydrogen treats cancer or improves nivolumab outcomes.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 32994821 · DOI: 10.3892/ol.2020.12121
Free full article on PubMed Central.
PubMed metadata and complete PubMed Central article; full-text extraction checked 8 August 2026.
10 August 2026
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