Eight years and 51 weeks ago I put that first mb12 "Under my tongue ..." (As sung by the Stones). I knew my life was changed in 1 hour flat. Over the next year I learned there are 4 b12 deficiencies, not one, and a whole lot more. Things separate out into components that have some at least logical discreteness. Indentification of effectiveness of current form of b12. When evaluated against the list of symptoms for which both active b12s are near 100% effective with suitable cofactors the identification of cyanocbl and hydrocbl goes like this. Cyanocbl was noticably but slightly effective for 6 of 300 symptoms. Hydroxycbl caused rapid onset of skin lesions that continued to spread as long as I took it. Hydroxcbl could not be continued long enough to determine if it had any effectiveness because of epithelial lesions and rapid neurological breakdown. A combination of methylb12 and adenosylb12 were effective for 175 of the 200 symptoms I had. Results will vary by person. However, hysdroxycbl and cyanocbl are not full effective for anybody. The degree of partial effectiveness varies considerably from 1 to maybe a dozen or two dozen symptoms affected partially. Idenitifcation of BODY - mb12 deficiency Identification of BODY - adb12 deficiency Identification of CNS/CSF- mb12 deficiency - large dose required to penetrate CNS Identification of CNS/CSF - adb12 - large dose required to penetrate CNS Indtification of sudden low potassium casued by methylation (healing) startup Idenitification of folate insufficiency Identification of paradoxical folate deficiency - folic acid Identification of paradoxical folagte deficiency - folinic acid Identification of paradoxical folate deficiency - vegetable food source folate Identification of paradoxical folate deficiency/insufficiency on small doses of Metafolin Identification of CNS/CSF - adb12 - normal dose or micro dose required to penetrate CNS coupled with neurological hypersensitivity to l-carnitine fumarate in limbic system all tied into neuronal ATP hypersensitivity and and increased sensitivity to dopamine variations some with Benzo side effects affecting dopamine receptors causing "Tolerance withdrawal". Hypothesized - CNS hypersensitivity to mb12 with microdoses but not to adb12. As some mb12 converts to adb12 to test this one would need to saturate on adb12 first and see what the mb12 response is after that. There is some indication that after adb12 and carnintine are in place that mb12 hypersensitivity may appear as it needs the functioning mitochondria as a prerequisite. Basically hydroxycbl, like cyanocbl, will affect some small percentage of the 300 symptoms, maybe limited to a number that can be counted on your fingers. Item 12 above is the only one about which there is any question of whether it can be substantially healed. So out of all of these building blocks and probably a few more not yet identified we can build the follwoing. Remember, there can be comodbidities and otehr complications that are not related and DON'T respond to the active b12 protocol. ME - Active b12 protocol 90% effective against these symptoms CFS - Active b12 protocol 90% effective against these symptoms FMS - Active b12 protocol 90% effecrtive against these symtpoms Pre-parkinson's leading to (hypothesized) Parkinson's - Carefully titratrated active b12 protocol affects this hugely, whether this leads to effectivbe healing or not is currently unknon. Pre- MS (hypothesized) leading to (hypothesized) MS (MS may not be anything really different from SubAcute Combined Degeneration except the specif-c nerves affected. Pre- ALS (hypothesized) leading to (hypothesized) ALS Pre- Alzheimer's (hypothesized) leading to (hypothesized) Alzheimer's Pre- SupraNuclearPalsy (hypothesized) leading to (hypothesized) SupraNuclearPalsy As these identifications are pragmatic, they also suggest possible treatment by correcting the funtional and/or absolute deficiencies. The first 3 can be reasonably well healed in a year with several more years to rehabilitate and finish healing. The question is what about these others, Item 4 for instance which is up right now. Does correcting the deficiencies in the end correct the problem? When does it become too late for repair and the disease becomes inevitable. Can it be moderated? Should it be treated even if the treatment is unpleasant or should the person simply take the path of avoidance of unpleasentness into the full blown illness? Can it be effectively treated any other way than ending the deficiencies? Lack of methylation happens with the lack of methylb12 and Methylfolate though these are not generally enough in themsleves and are recycled many times receiving methyl groups from Choline, TMG and other donors. SAM-e is a product of having methylb12 in the body and unless added as a separate item is part of a zero sum situation. I don't think there can be broken methylation in the presence of methylfolate and methyb12. This abnormal condition only occurs when the body is being starved for the real thing by being given pseudo vitamins like folic acid, cyanocbl and hydoxycbl or has paradoxical folate deficiency or other dietary and/or heriditary processing conditions. These three pseudo vitamins do not allow the body to normalize. Adenosylb12, methylb12 and Methylfolate allow the body to normalize. The intial stage of the body normalizing is for cell reproduction to turn on allowing general healing. 50mcg of methylb12 (1/4 of a sublingual 1mg ET or Jarrow) and 50mcg of adenosylb12 appear sufficient for widespread body healing but may not be enough for CNS normalization. As healing with mb12 and adb12 appears dose proportionate more of these allow somewhat more widespread healing to occur at the same time. ATP startup is often by far the "stronger" startup. It can independently trigger enough healing that didn't happen with mb12/metafolin that it can casue an increased need for potassium and additional Metafolin and additional mb12.