High serum B12 levels can be caused by a functional B12 deficiency. Based on testing in a lot of people, it looks as though this is pretty generally found in ME/CFS. It is consistent with the Glutathione Depletion-Methylation Cycle Block model for ME/CFS. What happens with a functional block is that the cells are not able to use B12 properly, so they export it back to the blood bound to haptocorrin. The liver cells are the only ones that can import this, and the residence time in the blood is about a week. So when a serum B12 measurement is made, it is dominated by this fraction of B12, which is not available to cells of the body other than the liver cells. It would be better to do a urine methylmalonate test to see if there is a functional (rather than an absolute) B12 deficiency. The serum B12 test is useful for detecting an absolute B12 deficiency (as can be caused by pernicious anemia or a transcobalamin deficiency or gut surgery or celiac or Crohn's disease), but it is not useful for detecting a functional B12 deficiency, which is what is found in ME/CFS.
A functional B12 deficiency means that even though you have enough B12 in your body, your cells are not able to use it properly. In ME/CFS, this is caused by depletion of glutathione. When glutathione goes too low, the affinity of the CblC complementation group (part of the intracellular processing pathway for B12) for B12 goes way down, based on research published last year from Korea. Thus, even though there is enough B12 present for normal operation, this group is not able to bind strongly enough to B12 to keep the rate of B12 processing high enough to meet the demands of the cells for methyl B12 and adenosyl B12, which are normally produced in the cells themselves from whatever form of B12 comes in from the diet and supplements.
This is confusing to the docs, who have not been trained to understand it. They know about absolute B12 deficiency, but not about functional B12 deficiency. When they see high serum B12, they tell people to stop taking it. Unfortunately, this is not the right advice. It's necessary to take relatively large dosages of B12 (such as 2 milligrams per day or so), either sublingually or by injection to get enough into the blood, together with oral methylfolate at about RDA levels (a few hundred micrograms per day). This is what is in the simplified methylation protocol, together with some other supplements to cover possible deficiencies of essential nutrients. Over a period of a few months, this usually overcomes the vicious circle involving glutathione depletion, functional B12 deficiency, methylation cycle partial block, and loss of folates from the cells.