December 19, 2014: I am editing this opening post because the thread is so long newcomers are not able to pick up certain points that keep coming up. First I want to make clear my main points. 1. I think people with CFS need to shorten the length of their activity times as much as they can down to 15-20 minute sessions followed by 10-15 minutes of total rest - meaning lying down with eyes closed, relaxing all muscles and letting thoughts drift. These amounts of time are not set in stone, but something to work towards. Anything that is not resting is an activity, including sitting in a recliner watching TV or using a laptop. This is because in these illnesses when the body is active it has to use all of its energy for the activity, and ROS, or oxidative stress, builds up in the mitochondria. The rest periods allow the body to lower the level of oxidative stress and reduce damage. A shorter activity time stops the ROS levels from building up as high. 2. I think that the cysteine/sulfate blood test will show when a person has gotten back to normal, the Genova oxidative stress analysis test is good but it has the normal reference range too high and I think the reference range from Rosemary Waring;s study should be used instead, with the Genova test. (The normal range in the Waring study is 0.09-0.12.) If a person raises their activity level too much before the cysteine/sulfate ratio is within Waring's normal range, they will be subject to relapse, but they always raise their activity level too soon, because the symptoms go away before they reach that point and they don't have, or haven't had until now, an objective test to tell when they should raise the activity level. 3. People who have less than a 3 hour window of activity are in a special category, and have more difficulty applying these ideas than people with a 3 or more hour of activity day. 4. People who have 4 hours of activity a day or more can speed up their recovery by having less activity time, but I don't think anyone who is able to have 3 hours of activity should have less than 3 hours of activity, because if possible, we need some activity. Here is the start of the original opening post: Can people with CFS get well? I mean really well. Cured. I think that they can, at least those who have a 3 hour window or more of activity. Those with less might be able to still get well, but it would take longer. But to get well you have to do one of the most difficult things ever - you have to rest when you don't feel tired. I have been thinking a great deal in the past few weeks about ME/CFS and it has been a great help to me in figuring out how to help my 2 sons with depression and schizophrenia, which I think are caused by the same thing that I think causes ME/CFS - mitochondrial dysfunction caused by oxidative stress. I want to thank Mary for sharing with me, the information she gave me has really helped me. According to my hypothesis, the reason people with ME/CFS never get well is because when they make changes in their protocol which increase their energy, they always use that energy to increase their activity instead of letting their body use it for healing. In other words, they increase their activity much too soon. I give a technical explanation for this below, but I want to talk about effective rest periods first so that people who aren't interested in the technical parts, or who don't have the energy to try to understand them right now, can read the practical parts first. I have seen a fair amount of talk about rest periods and how they can help but I think that they would be more effective if the activity time was shortened and broken up more. An ideal would be 10 minutes of activity followed by 10 minutes of total rest - in bed in a quiet darkened room, complete relaxation and just letting the mind drift, not active thinking. The closer a person can get to this ideal the more progress they should make. Of course it is impossible to always follow this, it's just something to reach for. I think a timer would be needed so as not to overdo the activity periods. This is very hard to do, because if you feel like you have energy you don't want to rest. Crashing is counterproductive and it shows that your protocol needs to be adjusted. A person with CFS should be taking rests all the time whether they feel tired or not. This is the opposite of graded exercise. These might seem like strong statements coming from someone who doesn't have CFS, but I think I have logical reasons to believe that they are true. I have seen an article where a person would rest for 15 minutes every hour or two and they were able to increase their total daily activity by 50% over a period of 6 months. That's where they made their mistake. If they kept the activity level the same for the whole 6 months they would have made a lot more progress, and maybe even have gotten well (this person started with 6 hours of activity), in my opinion, according to my hypothesis of what causes these illnesses. A lot of people here at PR have a smaller starting window, and it would take longer for them, but if a person keeps their activity level the same, the rate of improvement should increase as time goes on. The explanation is below. ******************************************************************************** This is the technical part, for those who want to skip it. The following is according to my hypothesis of how these illnesses are caused. The majority of energy in the body is produced by oxidative phosphorylation, which is when the electron transport chain takes electrons and uses the energy it gets from the electrons to move protons into the intermembrane space of the mitochondria, and the ATP synthase enzyme uses the energy to release ATP. This energy of the protons in the intermembrane space can be referred to as the proton motive force. This proton motive force is also used to make NADPH through the NNT enzyme. I show the protons as dollar signs instead of H+ after they move into the intermembrane space because I think of them like money in the bank that you can spend for healing or for activity. (and I am from the USA) The electron transport chain (ETC) is inhibited because it is full of iron-sulfur clusters, and iron-sulfur clusters are damaged by ROS, or reactive oxygen species, which include nitric oxide (NO) and hydrogen peroxide (H2O2) among others, i.e. oxidative stress. This is why you can't make enough ATP to have a normal life - the ETC is inhibited. The ETC also produces ROS; this is normal. A healthy person can create enough proton motive force to make ATP and enough NADPH to get rid of the ROS, but a person with CFS can't. There are other pathways to make NADPH in the mitochondria, but NNT is the major one and probably normally produces about 50% of the NADPH. So we have to keep ROS levels as low as possible to allow the body to produce ETC complexes (those are the ETC enzymes) with fewer damaged iron-sulfur clusters. Every minute of consecutive activity the ROS levels are increasing, and the rest breaks give the body a chance to lower the ROS levels. Long periods of consecutive activity will spike the ROS levels to a more damaging high. Of course this diagram is probably exaggerated, but you get the idea. It takes a little over 2 weeks to replace most of the ETC clusters, so every 2 weeks we want to see an improvement in the function of the ETC clusters, and that means the electron transport chain will work a little better every two weeks, as long as the person does not increase activity levels which will draw the extra energy into ATP instead of NADPH! How does NADPH get rid of ROS? NADPH is used to recycle GSSH back to GSH, or glutathione. So this is what is causing those low GSH/GSSH ratios. And the ratio you get when you are tested is the whole cell, not just the mitochondria, so you can be sure that your GSH/GSSH ratio in your mitochondria are worse than what the tests show. This problem with glutathione is also why detox becomes such an issue. So activity uses up the energy that could be used to fix the electron transport chain. By having frequent rests to allow the body to produce NADPH and lower ROS levels, the function of the ETC should improve over time, as long as the person doesn't use the extra energy for activity. Total bed rest is unhealthy, so some activity is needed. If a person has a large enough window of activity, they can decrease their activity time somewhat to speed up recovery. A 6 hour activity day could be decreased to 4 hours spread out over the whole day in little increments. If a person is at 3 hours or less, they should probably not decrease their activity, but just try to keep the activity periods very short as much as possible. There are other things that can be done to increase energy production such as supplements, which I talk about in other posts. The supplements will do no permanent good if the rest periods are not taken seriously.