HyCbl works poorly at best. It is about 1% as effective as AdoCbl and MeCbl. It is dependent upon already havimg some of each of those, plus l-carnitine fumarate and l-methylfoalte. CNS damage can continue for many people even while taking HyCbl.
I would like to combine several things that have come to my attention recently to once again discuss why hydroxycobalamin might not work to start a methylation cycle that is either blocked or depleted.
As I have mentioned multiple times through the years, in any given study on the use of hydroxycbl for the relief of several b12 deficiency symptoms and signs, approximately 1/3 of people in the study have zero effectivness on the symptoms or signs being studied. As the study symptoms are selected only from the list of those items KNOWN TO RESPOND to some extent to cyanocbl and hydroxycbl, about 1/3 of the total of all active mb12/adb12 deficincy symptoms, there are clearly some issues that prevent 1/3 of the people from responding.
So let's consider first several chains of reactions. Assume sufficiency of other needed items such as magnesium, l-carnitine and folate for this discussion.
methylb12 yields SAM-e
methylb12 yields glutathione
adenosylb12 yields ATP
hydroxycbl with assumed glutathione and assumed ATP and assumed SAM-e yields methylb12 and adenosylb12 in processes
The flaws in this are that these reactions can be deadlocked. It takes ATP produced by adb12 to produce adb12 and mb12. It takes glutathione to produce mb12 to produce glutathione. It takes ATP and mb12 to produce SAM-e to produce mb12
Without enough adb12 to produce ATP hydroxcbl doesn't produce adb12.
Without enough mb12 to produce glutathione, hydroxycbl doesn't produce glutathione.
Without enough SAM-e to produce mb12 hydroxycbl doesn't produce mb12 to produce SAM-e.
Without enough adb12 to produce ATP hydroxcbl doesn't produce mb12
Each of these are classic deadlock situations. The reactions are dependent upon sufficiency of the items or related items to be produced. In other words this has to act like a biochemical perpetual motion machine.
All of this happens because hydroxcbl competes for methyl groups instead of providing them and needs energy (ATP) to complete these up hill energy transactions. In each case hydroxcbl needs one or more of the items it is supposed to produce in order to produce the items.
Any ONE of these is enough to cripple hydroxycbl.
Methylb12 and adenosylb12 and Methylfolate start methylation and cell reproduction almost immediately and confirms it by depleting potassium within 3 days and epithelial tissues obviously starting healing in 10 days.
Adenosylb12 often starts mitochondrial functioning to improve starting within 10 minutes.
Hydroxycbl and folinic acid can take days to never to start methylation and cell reproduction, and then only paritally. This can be demonstrated as no duration of Hydroxcbl usage prevents mb12 startup responses. Hydroxycbl almost never adequately causes mitochondria to function fully. This can be demonstrated by no duration of hydroxycbl use preventing adb12 startup reponses.
After a period of hydroxycbl and folinic acid usage startup response of mb12 and adb12 tend to be more intense than if nothing at all had been taken. Many deficiency symptoms tend to worsen while these are taken.
Hydroxycbl usually needs lab tests to show effectiveness.
Adb12 and mb12 provide naked eye results almost always.http://forums.phoenixrising.me/show...n ... w-evidence
Will Marsden recently called my attention to a recent paper from Prof. Richard Deth's group (abstract below) that provides evidence from a rat experiment that major glutathione depletion blocks the conversion of hydroxocobalamin to methylcobalamin.
This has been one of the main propositions of the pathogenesis model that I have proposed for ME/CFS, i.e. the Glutathione Depletion--Methylation Cycle Block hypothesis. So far, this model has continued to be supported as more research is being completed.
One of the things this has brought home to me is that in cases in which glutathione or SAMe are extremely low, it will be difficult to get the methylation cycle going using hydroxocobalamin as the form of B12. This is the form included in the simplified protocol I have suggested, and it was found to be helpful for more than two-thirds of the people in our clinical study, but this may explain why some of the people did not receive benefit from this protocol.
Note that the protocol recommended by Freddd uses methylcobalamin as one of the forms of B12. Methylcobalamin is also used by Dr. Amy Yasko in some cases, depending on genomic polymorphisms. It is also used by Dr. Neubrander and other physicians participating in the DAN! project for treating autism.
Recently I have been suggesting that if the simplified protocol does not produce benefits within three months, either testing should be performed to determine why, or a change should be made in the protocol used. One possibility would be to add methylcobalamin, starting at low dosage and working up, as tolerated.