Hi, Aprilk1869.
Potassium was not measured in the clinical study that Dr. Nathan and I carried out. This study used hydroxocobalamin as the form of B12, so that the cells were able to control the amount converted to the active forms methylcobalamin and adenosylcobalamin.
I suspect that hypokalemia is more of a possibility when control is removed from the cells by giving high dosages of the active forms of B12 directly. The treatment used by Dr. Nathan and myself was derived from the full treatment program of Dr. Amy Yasko, who was trained as a naturopath. The philosophy of naturopathy seems to be to work with the natural system to the degree possible, rather than perturbing it by strong interventions, unless required. It may take longer to observe improvements with this approach, but the body may also have a better chance to make adjustments during the treatment.
Another advantage of the more "gentle" approach is that it is less likely to over drive the methylation cycle. I have seen evidence of this in biochemical test results from a couple of people who were taking large dosages of the active coenzyme forms of B12.
I have some concern about this because there are some people who do not have a well-functioning form of glycine N-methyltransferase, which is the "safety valve" on overdriving the methylation cycle. The impact of overdriving the methylation cycle in these people is not known, but I think it could have major effects on the methyltransferase reactions in the body, including methylation of DNA and hence, gene expression.
I understand why freddd uses the high dosages of the active forms of B12. His cells are not able to do the conversions from hydroxocobalamin well, apparently for genetic reasons. I think we have yet to learn how widespread this problem is among the ME/CFS community.
Best regards,
Rich
Hi Rich,
I understand why freddd uses the high dosages of the active forms of B12. His cells are not able to do the conversions from hydroxocobalamin well, apparently for genetic reasons.
That is the minor reason. 5mg sublingual would likely have sufficed if that was the only problem to be overcome. I share in common with others with CFS/FMS and that is a problem getting adequate cobalamin into my cerebral spinal fluid. CNS deterioration did not stop or even slow down with only sublingual mb12. Studies have demonstrated low CSF cobalamin levels in CFS and FMS and many other neurological diseases so studied. By titration trial of going from 1mg SC to 25mg SC injection I found that the threshold for CNS response was >6mg and <=7.5mg. This range has held up pretty well for others so trying. This is the amount needed to more or less halt the continuing neurological deterioration that was very serious because of decades of being ignored by doctors. It was ignored because they could suggest nothing better than either daily oral cyancbl or monthly injections of cyanocbl and I was already taking daily oral cycbl. To reverse this deterioration to a sizable degree REQUIRED, by titration trial, either 4x7.5mg SC injections daily or 3x10mg SC injections daily. Another man does well on 2x15mg SC injection. The Japanese have experimented with doses of about 50mg daily and hypothesized that some people have difficulty getting cobalamin into the CSF. How well this works depends upon the qualitative aspects of mb12 which differs amongst different batches of crystals. Others have found somewhat different schedules work for them, but all what you would call large and at least daily. There is a clue in the intrathecal injection trial the Japanese did for cord based diabetic neuropathy. They found that the benefit lasted as long as a high level of cobalamin was maintained in the CSF. This period was from 3 months to 4 years depending upon the person. Clearly from this study there is a great deal of difference in how fast cobalamin leaves the CSF. So, the dose and frequency needed is determined by 1- how difficult it is to get cobalamin into the CSF and 2- how quickly it is cleared from the CSF.
Then all my life was the added complication of folate deficiencies to various extents and lack of methylfolate, the only form to cross the BBB into the brain.
hydroxocobalamin as the form of B12, so that the cells were able to control the amount converted to the active forms methylcobalamin and adenosylcobalamin.
I would describe that a little differently. Rather than "control" by the cells "needs" I would say that the capacity of the channel to convert hycbl to mb12 and then to adenosylb12 is severely limited maintaining most of the cells in a starvation state for years if they ever catch up. If they could catch up one would expect that to be demonstrated by having the same lack of symptoms and zero response to mb12 and/or adb12 as healthy people without these symptoms have. It can be easily demonstrated that virtually nobody ever reaches that level on hycbl no matter how many years it goes on. In fact most (about 2/3) of the active b12 deficiency symptoms continue to worsen year after year while taking hycbl. Hycbl might be adequate to maintain a healthy normal person in that state but it sure doesn't get them back to that. That is all a matter of definition. If one excludes the 2/3 of deficiency symptoms on which hycbl does not work, then it can work pretty well except for the mystery diseases that have no cure as long as hycbl is assumed to be a fully functioning b12.
If you are concerned about the potential of "over methylation" then after the person has healed cut the maintenance dose back to 100mcg a day or whatever. As adb12 is not a methyl donor and requires an enzyme transaction to be converted to mb12 same as hycbl it should not even be talked about in terms of methylation.
As all the actual symptoms (not including personality characteristics) that are included on the symptoms list of "over-methylators" are mb12 and adb12 deficiency symptoms and that people with these deficiency symptoms typically also have about the same number of symptoms from the "under-methylator" list and that some symptoms, most notably and usually "depression" are included on both lists, I have a difficult time finding any actual discernable differences between hypothetical "under" and hypothetical "over" methylators. If "under-methylators" have b12 deficiency symptoms, why would "over-methylator" symptoms also be b12 deficiency symptoms from the same universe. If you can clear up this difficulty of definitions and come up with a real list of "over-methylator" symptoms that are not mb12/adb12 deficiency symptoms, or maybe a group of people that don't have most of both lists but only one sided sets of symptoms, the "over-methylator" hypothesis might gain some credibility. If it exists there has to be a difference somewhere.
A drop in potassium looks like it just might be the best indicator that cell reproduction has actually started up because effective methylation is restarted. How many more years or decades should a person wait for such startup and the healing it brings?
