This is really a continuation of NAD recipe, but I am introducing some important new ideas so I thought I would start a new thread. What I say here relates to my hypothesis that these illnesses (not only ME/CFS but some other chronic illnesses also) are caused by a vicious cycle of oxidative stress. I think I may have found the heart of the vicious cycle, and if I have, then it might be possible to overcome it. Next is the technical part: To get rid of H2O2, hydrogen peroxide, requires NADPH, which is used to return glutathione to its active state, and keep the GSH/GSSH ratio low. There are several mechanisms for recycling NADPH in the mitochondria: Malic enzyme, isocitrate dehydrogenase and NNT, or Nicotinamid Nucleotide Transhydrogenase. Here is a great illustration from an article found here, which I have added some comments to clarify. You can see the electron transport chain on the upper right hand side and how it transfers protons (H+) to the intermembrane space of the mitochondria. These protons are used by ATP synthase (shown at the top right) to change ADP to ATP, and also by NNT to change NADP to NADPH. It seems that NNT is supposed to produce about half of the NADPH in the mitochondria, but you can see that if the electron transport chain is inhibited, as I believe that it is in these illnesses, there are not enough protons in the intermemberane space to produce energy and recycle NADPH. Since iron-sulfur cluster synthesis begins and ends in the mitochondria, and iron-sulfur clusters are damaged by H2O2, and iron-sulfur clusters are a critical part of the electron transport chain, we have a vicious cycle here. Is this vicious cycle at the heart of these illnesses? If it is, we might be able to overcome these illnesses by increasing the amount of NAD in the mitochondria high enough to increase the concentration of NADH to push the ETC and raise the proton gradient to a sufficient level to feed both the NNT and the ATP synthase enzymes. So this brings us back to the NAD recipe. I have some new information relating to that, and I will post on it later. One last thing, I should mention that although taking malic acid might increase synthesis of NADPH in the peripheral parts of the body through the malic enzyme as seen in the illustration above, it doesn't really cross the BBB.