Background: Molecular hydrogen (H 2 ) is a biologically active gas that is widely used in the healthcare sector. In recent years, on-site H 2 gas generators, which produce high-purity H 2 by water electrolysis, have begun to be introduced in hospitals, clinics, beauty salons, and fitness clubs because of their ease of use. In general, these generators produce H 2 at a low-flow rate, so physicians are concerned that an effective blood concentration of H 2 may not be ensured when the gas is delivered through a nasal cannula. Therefore, this study aimed to evaluate blood concentrations of H 2 delivered from an H 2 gas generator via a nasal cannula. Methods: We administered 100% H 2 , produced by an H 2 gas generator, at a low-flow rate of 250 mL/min via a nasal cannula to three spontaneously breathing micro miniature pigs. An oxygen mask was placed over the nasal cannula to administer oxygen while minimizing H 2 leakage, and a catheter was inserted into the carotid artery to monitor the arterial blood H 2 concentration. Results: During the first hour of H 2 inhalation, the mean (standard error (SE)) H 2 concentrations and saturations in the arterial blood of the three pigs were 1,560 (413) nL/mL and 8.85% (2.34%); 1,190 (102) nL/mL and 6.74% (0.58%); and 1,740 (181) nL/mL and 9.88% (1.03%), respectively. These values are comparable to the concentration one would expect if 100% of the H 2 released from the H 2 gas generator is taken up by the body. Conclusions: Inhalation of 100% H 2 produced by an H 2 gas generator, even at low-flow rates, can increase blood H 2 concentrations to levels that previous non-clinical and clinical studies demonstrated to be therapeutically effective. The combination of a nasal cannula and an oxygen mask is a convenient way to reduce H 2 leakage while maintaining oxygenation.
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