Overload = overwhelming glutathione load. Since glutathione is part of the antioxidant system you might think of it as carrying an oxidative stress load. Maybe I should have said 'overloaded glutathione processes' or something like that. (I just updated the post above to try and clarify) This is a different way to think about the glutathione problem, rather than a focus on depletion, focusing on the load factors that are chronically depleting the glutathione system and eventually blocking its production. So treatments would seek first to identify and reduce total glutatione load, perhaps even before addressing the methylation cycle itself with the 'genetic bypass' strategy.