Drinking Hydrogen-Rich Water Alleviates Chemotherapy-Induced Neuropathic Pain Through the Regulation of Gut Microbiota
Lian N et al. · J Pain Res. 2021;14:681–691.
What kind of evidence is this?
Preclinical
Randomized four-group mouse oxaliplatin-neuropathy experiment with behavioral, microbiome and molecular analyses
Musculoskeletal and pain research
H₂-rich water
Not reported in this record.
Not reported in this record.
Methods at a glance
Female C57BL/6J mice receiving oxaliplatin or saline
Behavior n=10/group, microbiome n=6/group and biochemical assays n=5/group
20 days; oxaliplatin 3 mg/kg daily on days 1–5
Hydrogen-rich drinking water ad libitum throughout the 20-day experiment
H₂ dissolved in drinking water — H₂ only, not Brown’s gas and not inhalation.
Water was maintained at about 800–1,000 ppb dissolved H₂ and replaced daily.
Water preparation used pure H₂ at 400 mL/min for 10 minutes, then 100 mL/min continuously; this was preparation flow, not inhaled animal dose.
No O₂ was co-delivered as part of the drinking-water intervention.
Ordinary drinking water in saline- and oxaliplatin-treated mice
Outcomes and reported result
Mechanical paw-withdrawal threshold, gut-microbiota diversity and composition, cytokines, oxidative markers, LPS and TLR4
The article reports less mechanical hyperalgesia and changes in microbiota and LPS–TLR4-related measures. Several inflammatory and oxidative differences were observed in dorsal-root ganglia but not spinal cord or serum.
Allocation, H₂ preparation flow and concentration, main positive and null tissue findings, funding and limitations checked in the open-access full text.
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
Preclinical chemotherapy-toxicity model using only female mice, multiple microbiome and molecular outcomes, and no fecal-transplant test of causality.
Oxaliplatin-associated pain behavior in mice, not neuropathy prevention in cancer patients.
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: 33732014 · DOI: 10.2147/JPR.S288289
Open-access full text is available through PMC and the publisher.
Open-access PMC/publisher full text and PubMed record; no retraction or expression of concern was shown in the checked records on 7 August 2026.
2026-08-10