Traumatic brain injuries (TBIs) are a leading cause of death and disability. Sports-related TBIs are estimated to be more than several million per year. The pathophysiology of TBIs involves high levels of inflammation, oxidative stress, dysregulation of ion homeostasis, mitochondrial dysfunction, and apoptosis. There is also a reduction in cerebral blood flow, leading to hypoxia and reduced removal of metabolic waste, which further exacerbates the injury. There is currently no recognized effective medical treatment or intervention for TBIs, which may in part be due to the difficulty of drug delivery through the blood-brain barrier. Molecular hydrogen has recently emerged as a neuroprotective medical gas against cerebral infarction and neurodegenerative diseases including TBIs. Its small molecular size and nonpolar nature allow it to easily diffuse through the blood-brain barrier, cell membranes and subcellular compartments. Hydrogen has been shown to exert selective anti-inflammatory, antioxidant, and anti-apoptotic effects by regulating various transcription factors and protein phosphorylation cascades. Nitric oxide is another well-recognized medical gas that plays divergent roles in protecting from and in the recovery of TBIs, as well as in contributing to their pathophysiology and injury. Excessive activation of inducible nitric oxide synthase leads to excess inflammation and oxidative/nitrosative damage as well as a paradoxical nitric oxide depletion in the locations it is needed. Hydrogen regulates nitric oxide production and metabolism, which enhances its benefits while reducing its harms. A novel H2-infused, nitric oxide producing beverage, Hydro Shot, may have important neuroprotective benefits for TBIs. We report preliminary indications that Hydro Shot may be a meaningful adjuvant treatment for TBIs.

Background. Exercise performance and recovery are impaired by excessive levels of oxidative stress and inflammation. However, both reactive oxygen species (ROS) and inflammation improve exercise performance including mitochondrial ATP production and force of muscle contraction. They also are essential mediators in providing the benefits and training adaptations that occur from exercise. Nitric oxide (NO•) is a gaseous radical that increases blood flow via dilation of the blood vessels and also improves mitochondrial function. Therefore, NO• improves exercise performance and capacity, but only when produced at the right times and in the right locations. Excessive levels of NO• contribute to nitrosative stress due to the spontaneous reaction with superoxide to form toxic peroxynitrite. This decreases the ½ life of nitric oxide resulting in less NO• benefits and in cellular damage leading to impaired exercise performance. In contrast to conventional antioxidants and anti-inflammatories, molecular hydrogen (H2) has been demonstrated to exert selective antioxidant and anti-inflammatory effects by decreasing only excessive inflammation and reducing toxic oxidants without disturbing important signaling ROS, like NO•. Moreover, H2 can regulate NO• production, increase its circulating ½ life and beneficial NO• cycling, potentiate the bioactivity of NO•, and act as a NO• mimetic by increasing cGMP levels. At the same time H2 can prevent peroxynitrite formation and reduce the harm from NO• metabolism, such as lower nitrotyrosine levels. Methods. The effects of an H2-infused, nitric oxide-producing beverage (Hydro Shot) on nitric oxide production, blood flow, aerobic and anaerobic exercise, and cognitive function were assessed. Results. Ingestion of the functional beverage significantly increased production of NO• and a concomitant increase in blood flow. It also improved aerobic performance as measured by VO2, and anaerobic performance as indicated by delayed muscle fatigue, and increased peak torque during maximal isokinetic leg extensions. Additionally, the H2/NO• combination significantly improved indices of cognitive function including, focus, speed, plasticity, etc. Conclusion. The molecular crosstalk between H2 and NO•coupled with these preliminary results indicate that Hydro Shot is uniquely qualified for sports performance and exercise medicine and warrants additional clinical and mechanistic research.