Clinical Significance of Breath Hydrogen as an External Variable of Redox Environment

Hydrogen (H₂) is fermented by the intestinal microbiota, transferred to the blood according to the pressure gradient, and exhaled. Since H₂ is not produced or metabolized in human cells, alveolar H₂ saturates the entire human body, including cellular organelles such as mitochondria, owing to gas exchange in the lungs. The electron transport chain comprises a series of redox enzymes in the mitochondria of human cells that drive adenosine triphosphate (ATP) synthesis. The catalytic activity of electron-transport enzymes is optimized at certain electrochemical potentials, as is the hydrogen ion activity (pH). However, the human body is an aqueous solution, which must be electrically neutral. Membrane potentials exist between the inside and outside of human cells because of the unequal distribution of ions across the membrane. The single-electrode potential can only be assessed relative to that of another electrode (a reference electrode). We measured the electrochemical potentials relative to a standard hydrogen electrode (SHE), and found that H₂ partial pressure was a fundamental factor affecting the SHE, pH, and a reversible hydrogen electrode (RHE). The H₂ partial pressure is not a unit in the human body, therefore, breath H₂ is an external variable of the redox environment in the human body.