Methods_of_Application

Hydrogen (H₂) administration exhibits distinct pharmacokinetic profiles depending on the route of delivery—each with unique timing, tissue distribution, and physiological implications.

When H₂ is consumed through ingestion of hydrogen-rich water, absorption occurs rapidly, with peak concentrations typically reached within 2 to 15 minutes, depending on the species. The hydrogen enters the portal circulation but is largely metabolized by the liver or expelled via the lungs before it can reach systemic arterial blood. As a result, this route primarily delivers hydrogen to abdominal organs, particularly the liver, making it a promising method for targeting liver function or modulating the gut-liver axis. However, the systemic distribution of H₂ is minimal via this route.

In contrast, inhalation of hydrogen gas offers a more direct and widespread delivery method. Tissue saturation can occur rapidly—within 1 to 10 minutes depending on the concentration of inhaled hydrogen—with high-concentration inhalation producing proportionally greater hydrogen accumulation in tissues. Organs with high blood flow, such as the liver, spleen, and brain, reach peak levels quickly and also clear hydrogen relatively fast once exposure stops. Meanwhile, tissues with lower perfusion, such as skeletal muscle and fat, absorb hydrogen more slowly but retain it for longer periods. This route is ideal for achieving systemic effects, including potential benefits in neurological or muscular conditions, and allows for fine-tuning based on concentration and duration of exposure.

Hydrogen can also be produced endogenously via colonic fermentation of fermentable fibers and sugars by gut microbiota. This process leads to a delayed but often higher and more sustained rise in breath hydrogen compared to ingestion of hydrogen water. However, much of the hydrogen generated in the colon is exhaled or released as flatus, with only a fraction absorbed into circulation. While colonic fermentation offers a slower, more continuous source of hydrogen, its systemic impact is less consistent and depends heavily on diet composition and microbial ecology.

Together, these findings underscore that ingestion of hydrogen water is well-suited for targeting the liver and digestive organs; inhalation enables rapid and widespread tissue delivery, including to the brain and muscles; and fermentation may support low-level, long-term hydrogen exposure, although its bioavailability is limited and variable. Each route presents unique opportunities depending on the therapeutic goal.