Radical-driven methane formation in humans evidenced by stable isotope studies

Methane (CH₄), which is produced endogenously in animals and plants, was recently suggested to play a role in cellular physiology, potentially influencing the signaling pathways and regulatory mechanisms involved in nitrosative and oxidative stress responses. In addition, it was proposed that the supplementation of CH₄ to organisms may be beneficial for the treatment of several diseases, including ischemia, reperfusion injury, and inflammation. However, it is still unclear whether and how CH₄ is produced in mammalian cells without the help of microorganisms, and how CH₄ might be involved in physiological processes in humans. In this study, we provide first evidence of the principle that CH₄ is formed non-microbially in the human body by applying isotopically labeled methylated sulfur compounds, such as dimethyl sulfoxide (DMSO) and methionine, as carbon precursors to confirm cellular CH₄ formation. A volunteer applied isotopically labeled (²H and ¹³C) DMSO on the skin, orally, and to blood samples. The monitoring of stable isotope values of CH₄ convincingly showed the conversion of the methyl groups, as isotopically labeled CH₄ was formed during all experiments. Based on these results, we propose several hypotheses about endogenously formed CH₄ in humans, including physiological aspects and stress responses involving reactive oxygen species (ROS). Of particular importance is the potential to monitor CH₄ as an oxidative stress biomarker.