One of the things that became quite apparent a long time ago for CFS patients like myself was that intravenous glutathione helped a great deal. It was far from a cure but daily life was more bearable. This eventually led to richvank glutathione depletion/methylation block hypothesis. Currently, I am of the opinion that ME/CFS is just some undiagnosed Mast Cell Activation Disorder. Given that glutathione depletion happens in ME/CFS, I wanted to come up with a possible explanation within the context of mast cell activation disorders. I believe I have found one such explanation although I am not entirely sure it is the only one or even the right one. Upon activation, mast cells may potentially release hundreds of mediators. One of these mediators is Leukotriene C4. Leukotriene C4 is produced de novo by mast cells upon activation and for its synthesis both leukotriene A4 and glutathione are required. If mast cells are being constantly activated, for whatever reason, there is a decent possibility that glutathione might get depleted in the process. Once glutathione gets depleted, increased levels of reactive oxigen species (RIS) are generally observed. What is interesting is that ROS are also known activators of mast cells, resulting in what richvank liked to call a vicious circle. Within the context of mast cell activation disorders, this simple glutathione depletion process may thus explain why ME/CFS sufferers have increased levels of ROS.