Metabolomic Alterations Associated with Adjunctive Hydrogen Gas Inhalation During Concurrent Chemoradiotherapy in Locally Advanced Head and Neck Cancer: A Pilot Study
Chitapanarux I, Autsavapromporn N, Onchan W, Chakrabandhu S, Muangwong P, Duangya A, Lertsiriladakul T, Panya A, Paemanee A. · Cancers (Basel). 2026;18(14):2191.
Study at a glance
This small randomized study analyzed 19 people receiving chemoradiotherapy for advanced head and neck cancer. Adding daily hydrogen inhalation did not significantly improve treatment toxicity or the directly compared uric-acid change. Many metabolic measurements changed during treatment, but most comparisons were within each group. The findings do not establish a cancer-treatment or survival benefit.
Human
Adults aged 18–70 with locally advanced head and neck cancer, ECOG performance status 0–2, receiving curative concurrent chemoradiotherapy.
Hycellvator ET100 nasal-cannula inhalation for 1 hour daily, 1–2 hours before irradiation, across 30–33 fractions over 6–6.5 weeks. · Actual inspired H₂ concentration was not measured/reported. Gas purity or mixture values from the earlier pilot do not establish the exposure in this trial.
1 hour per session across 30–33 radiotherapy fractions over 6–6.5 weeks.
All between-group clinical comparisons in Table 2 were nonsignificant: chemotherapy delay 6/10 versus 3/9 (P = 0.25), median treatment duration 51.5 versus 48 days (P = 0.15), dermatitis P = 0.41, pharyngitis P = 0.31, mucositis P = 0.56, leucopenia P = 0.29, neutropenia P = 0.79 and thrombocytopenia P = 0.23. Direct change in uric-acid relative abundance was −39,917.15 ± 48,873.64 in controls versus −24,039.56 ± 13,924.30 with hydrogen (P = 0.11); these are relative-abundance units, not clinical serum concentrations. Separate within-group metabolite changes do not establish a hydrogen-specific effect. At February 2026 follow-up, 7/10 versus 8/9 had no disease, 2 versus 1 had local recurrence, and 1 versus 0 had disease-related death; these descriptive counts do not establish a survival or tumor-treatment effect.
Nineteen complete cases, heterogeneous cancer sites/stages and chemotherapy, no sham, and only toxicity assessors blinded. More carboplatin was used in the hydrogen arm. Most metabolomic comparisons were within-group; the direct uric-acid comparison was null. Positive-mode ionization, putative metabolite identities, single-hit pathway assignments and unvalidated in-sample ROC analyses limit mechanistic interpretation. Table 3 fold changes are pre/post ratios, so its direction labels do not directly represent post-treatment increases. Registration on 15 May 2024 followed recruitment starting in March 2024. This cohort recruited March 2024–January 2025 under TCTR20240515006, distinct from the 2023 pilot cohort represented by PMID 39493677 under TCTR20230627002.
What kind of evidence is this?
Human
Single-centre prospective assessor-blinded block-randomized two-arm pilot; no sham inhalation.
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
Adults aged 18–70 with locally advanced head and neck cancer, ECOG performance status 0–2, receiving curative concurrent chemoradiotherapy.
31 screened; 20 randomized (10 standard chemoradiotherapy, 10 chemoradiotherapy + hydrogen). Nineteen analyzed: 10 control and 9 hydrogen. One hydrogen participant withdrew consent at the 14th radiation fraction to seek herbal treatment.
1 hour per session across 30–33 radiotherapy fractions over 6–6.5 weeks.
Hycellvator ET100 nasal-cannula inhalation for 1 hour daily, 1–2 hours before irradiation, across 30–33 fractions over 6–6.5 weeks.
Hydrogen-containing generator gas. Source purity and mixture fractions were not numerically specified in this article.
Actual inspired H₂ concentration was not measured/reported. Gas purity or mixture values from the earlier pilot do not establish the exposure in this trial.
Reported generator gas flow 1.67 L/min; component fractions and measured patient uptake were not established.
Oxygen co-delivery and actual inspired oxygen fraction were not numerically established in the checked article.
The same intensity-modulated radiotherapy and weekly cisplatin 40 mg/m² or carboplatin AUC 2, without hydrogen or sham inhalation.
Outcomes and reported result
Exploratory serum metabolomic changes before and after chemoradiotherapy; no prospectively confirmed hierarchy of hydrogen-efficacy endpoints.
All between-group clinical comparisons in Table 2 were nonsignificant: chemotherapy delay 6/10 versus 3/9 (P = 0.25), median treatment duration 51.5 versus 48 days (P = 0.15), dermatitis P = 0.41, pharyngitis P = 0.31, mucositis P = 0.56, leucopenia P = 0.29, neutropenia P = 0.79 and thrombocytopenia P = 0.23. Direct change in uric-acid relative abundance was −39,917.15 ± 48,873.64 in controls versus −24,039.56 ± 13,924.30 with hydrogen (P = 0.11); these are relative-abundance units, not clinical serum concentrations. Separate within-group metabolite changes do not establish a hydrogen-specific effect. At February 2026 follow-up, 7/10 versus 8/9 had no disease, 2 versus 1 had local recurrence, and 1 versus 0 had disease-related death; these descriptive counts do not establish a survival or tumor-treatment effect.
The available main full text was reviewed for methods, results, limitations and declarations. Uncertainties, supplementary-source limits and conflicting findings are stated in this record.
Chemoradiotherapy toxicities occurred in both groups, without a significant reduction. The article describes inhalation as generally well tolerated, but does not establish long-term safety or preserved tumor control.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Nineteen complete cases, heterogeneous cancer sites/stages and chemotherapy, no sham, and only toxicity assessors blinded. More carboplatin was used in the hydrogen arm. Most metabolomic comparisons were within-group; the direct uric-acid comparison was null. Positive-mode ionization, putative metabolite identities, single-hit pathway assignments and unvalidated in-sample ROC analyses limit mechanistic interpretation. Table 3 fold changes are pre/post ratios, so its direction labels do not directly represent post-treatment increases. Registration on 15 May 2024 followed recruitment starting in March 2024. This cohort recruited March 2024–January 2025 under TCTR20240515006, distinct from the 2023 pilot cohort represented by PMID 39493677 under TCTR20230627002.
The selected head and neck cancer population and concurrent-treatment protocol only; biomarker changes do not establish clinical benefit.
No external funding reported in the funding statement. Helix Japan provided the research generator, disclosed separately.
Authors declare no competing financial interests. Helix Japan supplied the generator and reportedly had no role in design, conduct, analysis, interpretation, manuscript preparation or publication.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 42512258 · DOI: 10.3390/cancers18142191
Complete published article in PubMed Central / Europe PMC, including six main tables. Supplement descriptions were reviewed, but the raw supplementary metabolite tables were not separately checked.
AI-assisted editorial review of the available main full text, 29 October 2026. No independent clinical or statistical assessment has been performed.
Introduction; Methods 2.1–2.6; Results 3.1–3.7; Tables 1–6; Discussion; Conclusions; declarations.
AI-assisted editorial review of the available main full text, 29 October 2026. Complete published article in PubMed Central / Europe PMC, including six main tables. Supplement descriptions were reviewed, but the raw supplementary metabolite tables were not separately checked.
TCTR20240515006; registration reported as 15 May 2024, after recruitment began in March 2024. Ethics approval RAD-2566-0615, 30 January 2024.
29 October 2026
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