Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism
Kamimura N, Ichimiya H, Iuchi K, Ohta S. · NPJ Aging and Mechanisms of Disease. 2016;2:16008.
What kind of evidence is this?
Preclinical
Multi-part mouse, rat and HepG2-cell mechanistic study with short- and long-duration H₂ exposures
Metabolic and lipid health
H₂-rich water
Not reported in this record.
Not reported in this record.
Methods at a glance
Genetically diabetic db/db mice, diet-induced-obesity C57BL/6 mice, Sprague–Dawley rats and HepG2 cells.
Cohort sizes varied by experiment: selected gene/triglyceride assays used n=3–15; the lifespan experiment included normal-diet n=23, high-fat control-water n=38 and high-fat H₂-water n=36.
From hours/three days for pharmacokinetic and early-expression work to two weeks, four weeks and 74 weeks for animal outcomes.
Animals drank H₂-rich water ad libitum or received oral H₂-generating MgH₂; cell experiments used 10% or 50% H₂ atmospheres.
Ingested dissolved H₂ or H₂ generated in the stomach from MgH₂; separate cell-culture gas exposures were H₂ alone as the study gas, not Brown's gas.
Fresh H₂-water was supplied daily in closed vessels, but its dissolved-H₂ concentration and consumed volume were not reported in this article. MgH₂ doses included 0.09–90 mg/kg across experiments; cell atmospheres used 10% or 50% H₂.
Not applicable to the animal oral routes; no gas-flow rate was reported for cell exposures.
No co-administered O₂ dose or flow was reported.
Degassed water, Mg(OH)₂, normal/high-fat diets and cell conditions without H₂, depending on the experiment.
Outcomes and reported result
Hepatic microarray/pathway expression, PGC-1α/PPARα/FGF21 signaling, plasma triglycerides, body weight/food intake, oxidative signaling in cells and survival.
H₂ exposures shifted fatty-acid/steroid-metabolism gene pathways and increased early PGC-1α-related signaling in diabetic mice; oral MgH₂ reduced triglycerides in selected experiments. In high-fat-fed wild-type mice, H₂ water reduced triglycerides and increased survival (P=0.032) but did not change body weight or food intake. Cell data supported only an indirect, partly speculative 4-HNE/Akt/FoxO1 mechanism, and H₂ did not directly change several phosphorylation/expression comparisons.
The complete free PMC article, animal/cell methods, figures, long-term survival results and disclosures were checked for each administration route, reported and missing dose information, positive/null findings, funding and conflicts.
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
Complex multi-model study with heterogeneous cohorts/doses, many molecular endpoints, incomplete H₂-water concentration/intake reporting, small samples for several assays and mechanistic inference from HepG2 cells. Japanese public grants funded the work; authors declared no conflict.
Mechanistic and metabolic findings in rodents and liver-derived cells; they do not establish weight, lipid or longevity effects in humans.
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: 28721265 · DOI: 10.1038/npjamd.2016.8
Free full article in PubMed Central.
Complete PMC article and PubMed metadata; full-text extraction checked 9 August 2026.
2026-08-10