Hi. AH.
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.
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.
It is only since the work in Korea that we have an explanation for the observation of Lapp and Cheney in the late 80s and into the 90s that it was necessary to inject at least 2,000 or 2,500 micrograms of B12 per injection to have a therapeutic benefit from it in ME/CFS. It now makes sense. We have to overcome the low affinity due to glutathione depletion, and it takes a big dosage to do that. Eventually, glutathione comes back up, and the B12 demand becomes more normal.
It's good to know that B12 has not been found to be toxic, even at very high concentrations in the blood, so high serum B12 is not something to worry about. It is an indicator of functional B12 deficiency. Most of the B12 in the blood serum has actually been rejected from the cells because it couldn't be used. It is bound to haptocorrin, and the only cells that can pick it up are liver cells. It stays in the blood for about a week, which is why the levels can get so high if the cells are rejecting it. Eventually the liver picks it up and puts most of it out in the bile, which goes to the gut. It then has a chance to be bound to intrinsic factor and be reabsorbed. But if there is more than can be absorbed, the rest goes out in the stools.
I hope this helps.
Best regards,
Rich