B-12 - The Hidden Story

[undcvr]

Oh also I agree with Fredd about methyl over hydroxy even though I know Rich prefers hydroxy becos free methyl groups running around in your body can theorectically bind with Mercuy and carry it into the brain. You just dont get the same effects from hydroxy as you do from methyl and i think it is precisely becos of the methy group.

If you are concerned and if the detox process does start in you, I would recommend you take preformed Glutathione, just make sure to take it way from food and with a glass of water. With all the digestive probelms CFS have I can guarantee you that you are not producing enough stomach acids to chop up glutathione into any of its tri peptides. Glutathione will help with detox issues.

 

[Freddd]

Hi Fredd,
Thank you for you your response. However I dont know what this sentence means by "uneeded" when I was referring to our group who did the Metametrix test and have not improved after 8mths....doing Methyl B12/folinic acid.

Quote "Perhaps your group could benefit from trying the "unneeded" methylb12, adb12 and metafolin as part of the active b12" .....do you mean give up on Methyl B12 and change to adb12 and Metafolin

This next woman only needs B12, has no Intrinsic factor...not working after 8mths.....Do you mean she should try adb12 ...does she need Metafolin if her tests said NOT deficient.

Thank you
Susan

h

Hi Susan,

The remark about "unneeded" was my misunderstanding of your comment about only one person had testing showing that the methylb12 was needed. That's why talkining about these things helps hash out misunderstandings.

I don't know where you are at currently. What symptoms do you have from that list posted at the beginning of this thread. Also I am repeating the checklist form there.

Reasons B12 doesn't work for a person

• They take active b12 as an oral tablet reducing absorption to below 1%. A 1000mcg active b12 oral tablet might bind as much as 10mcg of b12. Again the b12 has to be squeezed through a keyhole that limits the amount and is subject to binding problems in the person whether genetic or acquired.
• They take an inactive b12, either cyanob12 or hydroxyb12. The research validating their use was primarily for reducing blood cell size in Pernicious Anemia, keeping the serum b12 level over 300pg/ml at the end of the period between injections. They make a statistically significant effect that can be seen in lab tests in a significant percentage of people compared to placebo. They do not heal most damage done by active b12 deficiencies and have little or no effect on the vast majority of symptoms. They may even block active b12 from receptor sites hindering the effects of real b12. They both cause a keyhole effect of having only a very limited amount (estimated at 10mcg/day) that can actually be bound and converted to active forms. They in no way increase the level of unbound active cobalamins which appear required for most healing.
  
  They do nothing beneficial in a substantial percentage of people (20-40%) while giving the illusion that the problem is being treated and if it doesnt work, oh well, thats the accepted therapy. There is no dose proportionate healing with these inactive b12s because it all has to go through this keyhole.
• Some people are totally incapable of converting these to active forms because they lack the enzyme.
  
• They take a sublingual tablet of active b12 and chew it or slurp it down quickly reducing absorption back to that same 1% and limited to binding capacity. With sublingual tablets absorption is proportionate to time in contact with tissues. Make it last 45-120 minutes under the upper lip or other placement. I performed a series of absorption tests comparing sublingual absorption to injection via hypersensitive response and urine colorimetry to determine rate of absorption is 15-25% for 45-120 minutes.,.
• Wrong Brand - Of the many brands of sublingual methylb12 only some are very effective. Some are completely ineffective and some have a little effect. Jarrow and Enzymatic Therapy mb12 sublinguals are 5 star as is Country Life Dibencozide (adenosylb12).
• For injectable methylb12, if it is exposed to too much light (very little light actually is too much) it breaks down. Broken down methylb12 is hydroxyb12. It doesnt work at healing brain/cord problems of those who have a presumed low CSF cobalamin level. That requires a flood of unbound methylb12 and adenosylb12 (2 separate deficiencies) that can enter by diffusion. Adenosyl12from sublinguals can ride along with injected methylb12.
• Some methylb12 just isn't as neurologically active as other batches of b12, injectable or tablets.
• They dont take BOTH active b12s.
• They dont take enough active b12s for the purpose, especially amounts needed to penetrate CSF by diffusion.
• Lack of methylfolate.
• Lack of other critical cofactors.
• Lack of basic cofactors.
• Taking glutathione or glutathione generating cofactors that induce an active b12 and methylfolate deficiency.

Check against all those reasons. At the very least Metafolin appears to be more likely to help produce results and has proven to be for a lot of people.

There isn't a test around that will accurately predict response or non-response to the 5 star active b12s and Metafolin, only a trrial of all of them with the basic cofactors and finally with the critical cofactors will accurately determine what does or doesn't work. And in advance nobody knows what combinations will do the trick. Some need all critical cofactors to get a response.

 

[Freddd]

Hi all, just want to share that the B12 therapy is definitely one of the cornerstones that has helped my recovery. It wasn't easy. I have tried B12 several times in the past but each time had to stop becos it was giving me problems, too many side effects. I would then forget about it and move onto something else until I come across it again or until someone mentions how it has helped them. I think this process of 'forgetting' about it is very important. I seem to go though it with almost all the supplements I take. It seems as if the body needs time to process the encounter with the new chemical and needs times to process the experience itself before it can take the B12 again. Its just that I notice the same thing with almost all the supplements that I have taken in the past that have at one point or another helped me eg, Artemisinin, Mussels, Reishi/Maitake, IP6, Arabinogalactan ... I am not trying to give supplements a spiritual component but rather I attribute it too the complex reactions that take place in us.

I would luv to get subcutaneous B12 and if someone can tell me where I can get it I would appreciate it.

Right now I am on

Deplin (methylfolate) 15mg
Leuvocorin (folinic acid aka formylfolate) 15mg
Methylcobalamin 5mg tabs from Source Naturals - as much as I need a day to get relief, can end up coming up to almost 10 tabs. *Note: This brand of B12 has been reviewed poorly on PR. But I think it more a statement of how much recovery I have made over all these years to be able to take a crappy supplement, or it may just be that if i switched to a better brand I wont need so many tabs a day.

Its been great though, together with the Valcyte, it is helping so much and I really feel better. All my cfs symptoms are slowly fading away. The Cycloferon is abit iffy but that is mainly my fault. Sadomachochism has never been my thing and I have yet to self-inject myself with anything even once ! No matter how much I try to convince myself that there is a greater benefit at stake.

I guess what I am trying to say is dont underestimate the detox process of B12. It can happen in as little as one dose, which if you think about is it really alot of B12. And it might put you off of it entirely. But then you might be missing the whole chance of benefiting from whatever recovery it might eventually bring you. I am sorry if cfs does not make more sense

Hi Undcvr,


Methylcobalamin 5mg tabs from Source Naturals - as much as I need a day to get relief, can end up coming up to almost 10 tabs. *Note: This brand of B12 has been reviewed poorly on PR. But I think it more a statement of how much recovery I have made over all these years to be able to take a crappy supplement, or it may just be that if i switched to a better brand I wont need so many tabs a day.

When I and the other 4 performed the 10 brand testing we were using single tablets only of 1 or 3 or 5mg. The one mg Enzymatic Therapy and 1 and 5mg Jarrow tablets blew our socks off while a single SOurce Naturals 5mg did nothing at all except allow our symptoms to return at the same rate as taking nothing at all. So I wonder what effectiveness you might have if you actually tried one of the brands we rated much higher. Also, I am remarkably unimpressed with folinic acid. It does not perform in any way similar to Metafolin. You might find that you do substantially better on the 5 star mb12 plus Country Life adenosylb12 (dibencozide) and Metafolin with the basic cofactors and the critical cofactors.

I would suggest you try the 5 star brands and titrate to body equilibrium then try the 50mg test to see if you need that much to get into the CSF/CNS beofre you actually try mb12 injections. First of all they are expensive. Second they are nowhere near as reliable as the 5 star mb12 brands for several reasons. And third, if you get an effective batch it might blow your socks off without telling you whehter you need body dosing or CNS dosing. And the CNS dosing needs to be tried after all cofactors and critical cofactors are in place or you will not know where to take it from there.

For many of us taking the active b12 protocol with the 5 star mb12 and adb12 and metafolin, glutathione was a total disaster. It was easily the worst supplement I have ever tried. Two years after my 6 week trial my nervous system still has not recovered to the point of functionality it had been at immediately before the trial and has left my need for Metafolin increased by a factor of 11 (8800mcg instead of 800mcg) to achieve the same results.

It's good that you made as much progress as you have. Good luck.

 

[undcvr]

When I and the other 4 performed the 10 brand testing we were using single tablets only of 1 or 3 or 5mg. The one mg Enzymatic Therapy and 1 and 5mg Jarrow tablets blew our socks off while a single SOurce Naturals 5mg did nothing at all except allow our symptoms to return at the same rate as taking nothing at all. So I wonder what effectiveness you might have if you actually tried one of the brands we rated much higher. Also, I am remarkably unimpressed with folinic acid. It does not perform in any way similar to Metafolin. You might find that you do substantially better on the 5 star mb12 plus Country Life adenosylb12 (dibencozide) and Metafolin with the basic cofactors and the critical cofactors.

Fredd, correct me if I am wrong but folinic acid in that form goes directly into the folate cycle and is usuable for dna sysnthesis where pyrimidines and thymines are produced. It is not methylfolate but formylfolate that is needed to complete this step. If that step is broken down then dna synthesis cannot occur. I know this becos Leuvocorin is given with a chemo drug because the chemo drug interferes with this step in the cycle. DNA systhesis is really important. How does methylfolate come into play here ?

 

[Freddd]

Fredd, correct me if I am wrong but folinic acid in that form goes directly into the folate cycle and is usuable for dna sysnthesis where pyrimidines and thymines are produced. It is not methylfolate but formylfolate that is needed to complete this step. If that step is broken down then dna synthesis cannot occur. I know this becos Leuvocorin is given with a chemo drug because the chemo drug interferes with this step in the cycle. DNA systhesis is really important. How does methylfolate come into play here ?

Hi Undcr,

correct me if I am wrong but folinic acid in that form goes directly into the folate cycle and is usuable for dna sysnthesis

Rich would be the person to ask on that. It was his explanation that convinced me that Folinic acid was worth giving a try. I simply replaced one tablet a day when I was on 4800 mcg per day of Metafolin and moved that down to 4000mcg plus 800mcg of folinic acid. In about 5 weeks I developed my telltale first "fast" symptom, angular cheilitis and right behind that deterioration of skin around my nails and on fingertips. Going back to 4800 Metafolin corrected angular cheilitis in less than a week whereas the fingertips take longer and are still improving, again, with the difference being felt in a day with angular chelilitis. That made me decide that 4800mcg was too close to the edge and moved it up a bit.

then dna synthesis cannot occur.

Exactly. And when I take folinic acid instead of some more Metafolin, I start having tissue formation problems that shows up first as angular cheilitis and then, looking at my history, increased MCV, acne type lesions, hypersensitivity to chemicals and foods, asthma and allergies, and nervous system deterioration. I can't explain it except that it happens for me that way and quite a sizable percentage of persons that got to their deficiencies in all sorts of different ways including vegetarian. I was also a vegetarian for 25 years or so, a bad bad bad choice which almost killed me. Without the mb12/adb12 from meat I couldn't get along on cyanocbl.

As Metafolin is relatively new, Merck having relatively recently inventing a process for making a stable methylfolate, there are a lot of old leftover therapies that may not have worked as well but worked better than folic acid. When experience and results contradict theory, I go with experience and results. Also, almost the entire medical understanding of b12 and folate is based on cyanocbl, hydroxycbl and folic acid as the backdrop and standard of comparison. A whole lot of biochemistry might look different if based on mb12,adb12 and Metafolin as the standard and backdrop. The fact that I am alive and in good health now demonstrates that.

In the USA we have two groups of people, of possibly near equal size; group one without loads of symptoms on the list, no mysterious neurological or other mysterious maladies and no 2 hour response to a 5 star mb12 and group two with dozens to hundreds of "non-specific" symptoms on the list, lots of mysterious maladies neurological and otherwise and at least some response to a 5 star mb12 within 2 hours. I've spent most of my working life involved with group health insurance and HMOs (before they became a dirty word by the abuses committed in becoming "profit centers" instead of community based non-profit hospitals and Health Maintenance Organizations. By converting all these community non-profit hospitals and HMOs to "profit centers" we have increased our medical costs 25-50%. I had a box seat to the MaxiCare debacle. http://publishing.cdlib.org/ucpress...020tn&chunk.id=ch05&toc.id=ch05&brand=ucpress

 

[richvank]

Why doesn't hydroxocobalamin work for Freddd and some other folks?

Hi, Freddd and the group.

I've been puzzling over this question: Why doesn't hydroxocobalamin work for Freddd and some others, while methylcobalamin and adenosylcobalamin do?

Now I have a possible answer, which I would like to share.

First, as I have reviewed in the past, the normal transport of B12 and its import into the cells involves its binding with transcobalamin for carriage in the blood, and the linking of transcobalamin with its receptors on the cells for bringing the B12 into the cells. Then, the normal B12 processing within the cells involves stripping off the beta ligand (methyl-, adenosyl-, aquo- or cyano-) and reconstructing appropriate amounts of methylcobalamin and adenosylcobalamin for use by the cells.

Freddd has noted that the normal intracellular B12 processing does not work well in his case because of an inborn error of metabolism (i.e., a genetic mutation in one or more of the intracellular B12 processing enzymes).

Fortunately, by a persistent and exhaustive effort on his part over many years, he has found that he can compensate for this deficit by direct application of large dosages of both methylcobalamin and adenosylcobalamin (together with methylfolate and certain cofactor nutrients), delivered sublingually (or by injection) directly into the bloodstream. This does the trick for him, and for a number of other people with whom he has interacted. On the other hand, he reports that hydroxocobalamin doesn't work for him.

Meanwhile, based on the work of Dr. Amy Yasko, primarily in autism, I proposed use of sublingual hydroxocobalamin as part of the socalled "Simplified Treatment Approach" for ME/CFS. Clinical study of this protocol has shown that about two-thirds of people screened to have an "official" diagnosis of ME/CFS, including post-exertional fatigue and malaise, experienced a significant improvement from this protocol over a period of several months.

So how can this be?

Well, it seems likely that Freddd's treatment approach is bypassing the normal transport, import and processing of B12, and instead is relying on diffusion of methylcobalamin and adenosylcobalamin directly through the phospholipid bilayer plasma membranes of the cells to deliver these cofactor forms of B12 for use by the cells without further processing. I think this is the key to the explanation of the failure of hydroxocobalamin to work for Freddd.

It is known that in order for a molecule to diffuse through the cell membrane, it is important that it be uncharged, i.e. a neutral molecule. The reason for this is that if a molecule in an aqueous (i.e. water) solution (such as blood plasma) has a net positive or negative charge, the surrounding water molecules will orient themselves so that their oppositely charged ends will be closer to the molecule, on the average, forming a "cage" around the molecule. In order to pass through the cell membrane, the molecule would have to shed this cage, but the binding energy of these water molecules makes it difficult for this to happen. Therefore, charged molecules generally do not pass through cell membranes readily. ( There are exceptions to this, involving "porins," but they are not involved with B12, as far as I know.)

(Note that this phenomenon occurs because a water molecule has a dipole moment; that is, its center of positive charge is separated by a small distance from its center of negative charge. This results from the shape of the molecule, in which the two hydrogen atoms are not at 180 degrees from each other, but are unsymmetrically located on the oxygen atom as a result of the shapes of the electron orbitals that are involved in the bonding, which gets into quantum mechanics, and I will spare you that! Anyway, this is the reason why a water molecule has a dipole moment.)

O.K., here's the point of giving you all this gobbledygook:

Hydroxocobalamin, when it enters the blood plasma, mostly becomes aquacobalamin by picking up a hydrogen ion from the plasma. That is, instead of hydroxide being bound to the cobalamin, there will now be a complete water molecule bound to it. (This occurs because there's a chemical equilibrium established between aquacobalamin and hydroxocobalamin. The so-called "pKa" value for aquacobalamin is 7.8 while the pH of the blood is normally about 7.4 . This means that the equilibrium will be shifted toward formation of aquacobalamin.) But the hydrogen ion brings with it a positive charge, and that causes the aquacobalamin molecule to have a net positive charge, because hydroxocobalamin is a neutral molecule. So now you can probably see where I'm going with this. When hydroxocobalamin is used as the B12 supplement, we are really dealing in the blood primarily with aquacobalamin, a charged molecule, and charged molecules don't diffuse readily through cell membranes. So I suggest that that's why hydroxocobalamin supplementation doesn't work for Freddd or for others who are depending on direct delivery of the B12 coenzymes to their cells.

Now, why does hydroxocobalamin work for the other people? Well, I suggest that they are able to utilize normal transcobalamin delivery and normal processing of B12 inside their cells. They put hydroxocobalamin into their blood via the sublingual route. It rapidly converts mostly to aquacobalamin. However, transcobalamin will bind to all the forms of cobalamin, and it is therefore able to carry the aquacobalamin into the cells, where it then undergoes normal processing to form methycobalamin and adenosylcobalamin for use by the cells.

You might ask why it's necessary for this latter group to put the hydroxocobalamin into their bodies by the sublingual route, rather than just taking it orally. I think the answer to this question is that the absorption from the gut (using intrinsic factor) has a limited capacity, and the amount of B12 that is needed in ME/CFS or autism to overcome the hijacking by toxins in the absence of sufficient protection by glutathione (because it is depleted) is much greater than can be put into the blood by the intrinsic factor mechanism.

I think this can explain this seeming paradox that has bedeviled us (or me, at least!) for such a long time.

Best regards,

Rich

 

[Freddd]

Hi, Freddd and the group.

I've been puzzling over this question: Why doesn't hydroxocobalamin work for Freddd and some others, while methylcobalamin and adenosylcobalamin do?

Now I have a possible answer, which I would like to share.

First, as I have reviewed in the past, the normal transport of B12 and its import into the cells involves its binding with transcobalamin for carriage in the blood, and the linking of transcobalamin with its receptors on the cells for bringing the B12 into the cells. Then, the normal B12 processing within the cells involves stripping off the beta ligand (methyl-, adenosyl-, aquo- or cyano-) and reconstructing appropriate amounts of methylcobalamin and adenosylcobalamin for use by the cells.

Freddd has noted that the normal intracellular B12 processing does not work well in his case because of an inborn error of metabolism (i.e., a genetic mutation in one or more of the intracellular B12 processing enzymes).

Fortunately, by a persistent and exhaustive effort on his part over many years, he has found that he can compensate for this deficit by direct application of large dosages of both methylcobalamin and adenosylcobalamin (together with methylfolate and certain cofactor nutrients), delivered sublingually (or by injection) directly into the bloodstream. This does the trick for him, and for a number of other people with whom he has interacted. On the other hand, he reports that hydroxocobalamin doesn't work for him.

Meanwhile, based on the work of Dr. Amy Yasko, primarily in autism, I proposed use of sublingual hydroxocobalamin as part of the socalled "Simplified Treatment Approach" for ME/CFS. Clinical study of this protocol has shown that about two-thirds of people screened to have an "official" diagnosis of ME/CFS, including post-exertional fatigue and malaise, experienced a significant improvement from this protocol over a period of several months.

So how can this be?

Well, it seems likely that Freddd's treatment approach is bypassing the normal transport, import and processing of B12, and instead is relying on diffusion of methylcobalamin and adenosylcobalamin directly through the phospholipid bilayer plasma membranes of the cells to deliver these cofactor forms of B12 for use by the cells without further processing. I think this is the key to the explanation of the failure of hydroxocobalamin to work for Freddd.

It is known that in order for a molecule to diffuse through the cell membrane, it is important that it be uncharged, i.e. a neutral molecule. The reason for this is that if a molecule in an aqueous (i.e. water) solution (such as blood plasma) has a net positive or negative charge, the surrounding water molecules will orient themselves so that their oppositely charged ends will be closer to the molecule, on the average, forming a "cage" around the molecule. In order to pass through the cell membrane, the molecule would have to shed this cage, but the binding energy of these water molecules makes it difficult for this to happen. Therefore, charged molecules generally do not pass through cell membranes readily. ( There are exceptions to this, involving "porins," but they are not involved with B12, as far as I know.)

(Note that this phenomenon occurs because a water molecule has a dipole moment; that is, its center of positive charge is separated by a small distance from its center of negative charge. This results from the shape of the molecule, in which the two hydrogen atoms are not at 180 degrees from each other, but are unsymmetrically located on the oxygen atom as a result of the shapes of the electron orbitals that are involved in the bonding, which gets into quantum mechanics, and I will spare you that! Anyway, this is the reason why a water molecule has a dipole moment.)

O.K., here's the point of giving you all this gobbledygook:

Hydroxocobalamin, when it enters the blood plasma, mostly becomes aquacobalamin by picking up a hydrogen ion from the plasma. That is, instead of hydroxide being bound to the cobalamin, there will now be a complete water molecule bound to it. (This occurs because there's a chemical equilibrium established between aquacobalamin and hydroxocobalamin. The so-called "pKa" value for aquacobalamin is 7.8 while the pH of the blood is normally about 7.4 . This means that the equilibrium will be shifted toward formation of aquacobalamin.) But the hydrogen ion brings with it a positive charge, and that causes the aquacobalamin molecule to have a net positive charge, because hydroxocobalamin is a neutral molecule. So now you can probably see where I'm going with this. When hydroxocobalamin is used as the B12 supplement, we are really dealing in the blood primarily with aquacobalamin, a charged molecule, and charged molecules don't diffuse readily through cell membranes. So I suggest that that's why hydroxocobalamin supplementation doesn't work for Freddd or for others who are depending on direct delivery of the B12 coenzymes to their cells.

Now, why does hydroxocobalamin work for the other people? Well, I suggest that they are able to utilize normal transcobalamin delivery and normal processing of B12 inside their cells. They put hydroxocobalamin into their blood via the sublingual route. It rapidly converts mostly to aquacobalamin. However, transcobalamin will bind to all the forms of cobalamin, and it is therefore able to carry the aquacobalamin into the cells, where it then undergoes normal processing to form methycobalamin and adenosylcobalamin for use by the cells.

You might ask why it's necessary for this latter group to put the hydroxocobalamin into their bodies by the sublingual route, rather than just taking it orally. I think the answer to this question is that the absorption from the gut (using intrinsic factor) has a limited capacity, and the amount of B12 that is needed in ME/CFS or autism to overcome the hijacking by toxins in the absence of sufficient protection by glutathione (because it is depleted) is much greater than can be put into the blood by the intrinsic factor mechanism.

I think this can explain this seeming paradox that has bedeviled us (or me, at least!) for such a long time.

Best regards,

Rich

Hi Rich,

This looks like another BINGO for explaining the selective nature of the diffusion process. Now let's take it to the next level, diffusion into the CSF/CNS. This takes a much higher dose into serum raising peak serum quite a lot higher than body only effective doses. As the knowledge that at least some disorders are associated with low CSF/CNS cobalamin levels, such as CFS and FMS, why would some people have so much difficulty getting cobalamin into the CSF and/or keeping it there? I would guess that the same differential effect between charged and uncharged cobalamins would exist diffusing into the CSF thereby favoring methylb12 and adenosylb12, which both diffuse into the CSF in a similar time and if anything the adenosylb12 appears possibly a little quicker at it.


Well, it seems likely that Freddd's treatment approach is bypassing the normal transport, import and processing of B12, and instead is relying on diffusion of methylcobalamin and adenosylcobalamin directly through the phospholipid bilayer plasma membranes of the cells to deliver these cofactor forms of B12 for use by the cells without further processing. I think this is the key to the explanation of the failure of hydroxocobalamin to work for Freddd.

(Note that this phenomenon occurs because a water molecule has a dipole moment; that is, its center of positive charge is separated by a small distance from its center of negative charge. This results from the shape of the molecule, in which the two hydrogen atoms are not at 180 degrees from each other, but are unsymmetrically located on the oxygen atom as a result of the shapes of the electron orbitals that are involved in the bonding, which gets into quantum mechanics, and I will spare you that! Anyway, this is the reason why a water molecule has a dipole moment.)

As H2O has a bond angle of 104.5 degrees it is a LONG way from 180 degrees. Takes me back to chemistry class and calculating bond angles, bond energy and such.

When hydroxocobalamin is used as the B12 supplement, we are really dealing in the blood primarily with aquacobalamin, a charged molecule, and charged molecules don't diffuse readily through cell membranes.

And that is presumably equally true for everybody. So adenosylb12 appears to have similar diffusion characteristics to methylb12 so presumably it is also a neutral charge.

 

[Freddd]

Why B12 Deficiency is a HIDDEN Problem

There are multiple contributing causes for b12 deficiencies to be a hidden problem. Based on what the two "official" b12s, cyanocbl and hydroxycbl, only about 100 symptoms are recognized as those are the ones that that the periodic (1 per month to 1 per 3-monthsi njection) of inactive b12s affect. The other 200 or so symptoms that generally only respond well to active b12s are totally ignored and are equally non-specific. None of these symptoms are specifically b12 deficiency. Many are folate or folate and b12 deficiencies. Many have entirely different possible causes. Many people with b12 deficiency are accused of being alcoholics by their doctors despite their denials. Many b12 deficiency symptoms are also low testosterone symptoms ignoring the fact that b12 deficiency can cause low testosterone. CFS and FMS, were considered such things as "yuppie flu" or "imaginary woman's disease" rather that giving them credibility leading to much mistreatment. Failure to recognize the documented CNS/CSF deficiency of cobalamin in CFS/FMS leads to all sorts of hypothesis.

As there are 4 distinct sets of b12 deficiency symptoms and a distinct set of folate deficiency symptoms, and that officially there is one size fits all b12 deficiency that in the view of many doctors starts and stops with pernicious anemia (IF insufficiency) and macrocytotic anemia, the resulting anemia from IF insufficiency. This ignores totally that many people have major neurological involvement up to and including permanent damage completely without anemia and that the major problem set can be limited to the central nervous system.

It's hidden because of the current trend to diagnose from tests. The only tests available; serum cobalamin, serum Hcy, uMMA and serum bound cobalamin can tell you if you are terribly deficient with biological breakdown well under way or serum levels so low it's bound to be trouble but on th other hand they can't indicate sufficiency. They don't have "deficiency symptom free" levels. As average serum levels over 700pg/ml and some over 1500pg/ml were found in studies that accept participants by symptoms rather than test results, a "high" serum marker of 900-100pg/ml is nonsense. If 1100pg/ml is "high" how can methylb12 responsive neuropathies exist above 1500pg/ml with low uMMA and low Hcy? Going by test result rather than the positive responses would have excluded more than 60% of the positive responders.

 

[richvank]

Hi Rich,

This looks like another BINGO for explaining the selective nature of the diffusion process. Now let's take it to the next level, diffusion into the CSF/CNS. This takes a much higher dose into serum raising peak serum quite a lot higher than body only effective doses. As the knowledge that at least some disorders are associated with low CSF/CNS cobalamin levels, such as CFS and FMS, why would some people have so much difficulty getting cobalamin into the CSF and/or keeping it there? I would guess that the same differential effect between charged and uncharged cobalamins would exist diffusing into the CSF thereby favoring methylb12 and adenosylb12, which both diffuse into the CSF in a similar time and if anything the adenosylb12 appears possibly a little quicker at it.


Well, it seems likely that Freddd's treatment approach is bypassing the normal transport, import and processing of B12, and instead is relying on diffusion of methylcobalamin and adenosylcobalamin directly through the phospholipid bilayer plasma membranes of the cells to deliver these cofactor forms of B12 for use by the cells without further processing. I think this is the key to the explanation of the failure of hydroxocobalamin to work for Freddd.

(Note that this phenomenon occurs because a water molecule has a dipole moment; that is, its center of positive charge is separated by a small distance from its center of negative charge. This results from the shape of the molecule, in which the two hydrogen atoms are not at 180 degrees from each other, but are unsymmetrically located on the oxygen atom as a result of the shapes of the electron orbitals that are involved in the bonding, which gets into quantum mechanics, and I will spare you that! Anyway, this is the reason why a water molecule has a dipole moment.)

As H2O has a bond angle of 104.5 degrees it is a LONG way from 180 degrees. Takes me back to chemistry class and calculating bond angles, bond energy and such.

When hydroxocobalamin is used as the B12 supplement, we are really dealing in the blood primarily with aquacobalamin, a charged molecule, and charged molecules don't diffuse readily through cell membranes.

And that is presumably equally true for everybody. So adenosylb12 appears to have similar diffusion characteristics to methylb12 so presumably it is also a neutral charge.

Hi, Freddd.

Yes, both methycobalamin and adenosylcobalamin have neutral (uncharged) molecules. They are fairly large in size, though, and are not fat-soluble, and that will limit how well they can diffuse through phospholipid membranes.

I would like to better understand the transport of B12 into the brain, also. I've looked over the published work a little, as I suppose you have, too. It looks as though there is some evidence of active transport of B12 across the blood-brain barrier, but it doesn't look as though it's very well understood yet. Since the normal transport of B12 in the blood involves binding to transcobalamin, I'm guessing that there would have to be transcobalamin receptors involved in the blood-brain barrier if there is active transport. Then I would also guess that cells in the brain would have the usual B12 processing enzymes.

In your case, given the genetic issue, it would seem that the mutation would also be present in the cells in the brain, so the usual processing of B12 would not work so well there, either. It would seem, then, that the alternative for getting coenzyme B12 forms into the cells of the brain would again be diffusion, in this case across the blood-brain barrier as well as across the cell membranes. Given that the blood-brain barrier is a "tighter" effective barrier than an ordinary cell membrane, and that there would be two effective barriers to surmount, including the cell membrane, it would make sense (based on Fick's first law of diffusion) that a higher concentration gradient would be needed to push the B12's into the brain than is needed to push them into other cells of the body that are not protected by the blood-brain barrier, and that would explain why the serum concentration of the B12's has to be raised higher to move them into the brain at effective rates. And again, the neutral B12 forms would be much more easily diffused into the brain than would aquacobalamin, descended from hydroxocobalamin. So that would be a qualitative sort of explanation, which I think is consistent with your experience.

Best regards,

Rich

 

[Freddd]

Hi, Freddd.

Yes, both methycobalamin and adenosylcobalamin have neutral (uncharged) molecules. They are fairly large in size, though, and are not fat-soluble, and that will limit how well they can diffuse through phospholipid membranes.

I would like to better understand the transport of B12 into the brain, also. I've looked over the published work a little, as I suppose you have, too. It looks as though there is some evidence of active transport of B12 across the blood-brain barrier, but it doesn't look as though it's very well understood yet. Since the normal transport of B12 in the blood involves binding to transcobalamin, I'm guessing that there would have to be transcobalamin receptors involved in the blood-brain barrier if there is active transport. Then I would also guess that cells in the brain would have the usual B12 processing enzymes.

In your case, given the genetic issue, it would seem that the mutation would also be present in the cells in the brain, so the usual processing of B12 would not work so well there, either. It would seem, then, that the alternative for getting coenzyme B12 forms into the cells of the brain would again be diffusion, in this case across the blood-brain barrier as well as across the cell membranes. Given that the blood-brain barrier is a "tighter" effective barrier than an ordinary cell membrane, and that there would be two effective barriers to surmount, including the cell membrane, it would make sense (based on Fick's first law of diffusion) that a higher concentration gradient would be needed to push the B12's into the brain than is needed to push them into other cells of the body that are not protected by the blood-brain barrier, and that would explain why the serum concentration of the B12's has to be raised higher to move them into the brain at effective rates. And again, the neutral B12 forms would be much more easily diffused into the brain than would aquacobalamin, descended from hydroxocobalamin. So that would be a qualitative sort of explanation, which I think is consistent with your experience.

Best regards,

Rich

Hi Rich,

I would like to better understand the transport of B12 into the brain, also. I've looked over the published work a little, as I suppose you have, too. It looks as though there is some evidence of active transport of B12 across the blood-brain barrier, but it doesn't look as though it's very well understood yet.

You can say that again. In reading the high dose mb12 research I have found that they hypothesize that there is some kind of damage or malfunction to the unknown presumed active transport system. Much b12 research bases many of their conclusions on assumptions that have been passed on like a computer virus or research based on previous faulty research and invalid assumptions and just plain misunderstandings which ends up making the symptoms unrecognizable and undiagnosable

As far as the high dose mb12 research going on in a pragmatic sense of what works they don't know as well as we do here and at wrongdiagnosis. There is no research going on with adenosylb12 and CSF/CNS penetrating doses that I have found. Very little of the research includes cofactors and when it does it is almost always folic acid and B6 instead of Metafolin and P-5-P. You appear to have put together the best explanation of the diffusion model I have seen yet, and there is very little on the diffusion model. I don't know if it helps to refine this model for you to know that adb12 appears to join with mb12 as far as the diffusion gradient is concerned so that a sizable dose of mb12 injected will allow adb12 from a sublingual to accompany the mb12 into the CNS/CSF with proper peak timing in satisfactory amounts. Also, that too much adb12 in the CNS/CSF compared to the amount of mb12 over a multiweek period appears to cause neurological and neuropsych problems similar to CSF/CNS mb12 deficiency which is different from the volatility caused by mb12 during healing.

Further, there is a "threshold" effect on the mb12 dosage that is needed to penetrate the CNS/CSF. While the normal sublingual doses appear to produce some limited CSF/CNS effects even in those with a clear problem in that area, this effect tops out at about 2-3mg absorbed dose and then there is a sudden one time increase of effect at between 5-10mg injected SC depending upon the person. Above that more does not appear to make any difference except for small increases in duration. So I have found that 7.5mg 4 times per day or 10mg 3 times per day to be equally effective. Another person has found that 15mg twice a day or 10mg 3 times per day also performs as well for him. The duration of activity is different from person to person. Some appear to need such an injection only each few days for CNS/CSF effectiveness while others once a day and others 2-4 times per day. This appears in line with the diabetic neuropathy intrathecal injections lasting from less than 3 months to more than 12 months.

The problems with much of the research being done in awareness of the decreased CSF cobalamin levels is that the studies they do are with hydroxcbl or cyanocbl (plus folic acid and B6) which fail to have any significant effectiveness as the explanation you present would predict AND they do it with doses that would not be sufficient if done with mb12 and/or adb12 in any case, to reach a CSF penetrating diffusion gradient.

After my analysis of all the systemic failures I could find for not being able to diagnose blatant B12 deficiencies, which was the "automatic" presumed diagnosis by most all my doctors, until they saw test results and found out I was taking 1mg of cyanocbl daily orally at which time they said "impossible" because of their incorrect assumptions and understandings. Then I set out to eliminate all the assumptions possible and see if the probability of results could be increased which lead to the checklist of why b12 therapies frequently don't work. So assumptions of folic acid being a satisfactory folate for everybody turned out to be known to be false even though very few docs know that, or act on it. I worked through every assumption, including b6 versus p-5-p and so on. Also I examined the assumption that the typical diet provides satisfactory vitamin and nutrient content which was blatantly untrue in the presence of active b12s and active folate as those appear to be the most limiting factors, but not only limiting factors.

If b6 instead of p-5-p does limit effectiveness, it is less frequent than any of the b12 or folate limitations and only if those things are sufficient is it noticeable, usually. I eliminated them anyway in order to maximize probability of results.

 

[bluezone]

I recently discovered a new probiotic called L. reuteri and after some initial research it seems that it is the only probiotic that seem to be able to produce both folate and cobalamin. I have started taking it a low dose, as I have a couple of stomach isues that I am dealing with. I was wondering if anyone has ever tried it or got any more information on it; and this is a stretch, but perhaps there is enough evidence to add it to the methylation protocol as the last article seems to suggest that it might be of benefit to those with b12 problems. Anyway, here are some links to a couple of papers on it:

http://www.mendeley.com/research/vitamin-b12-synthesis-in-lactobacillus-reuteri/

http://mic.sgmjournals.org/cgi/content/abstract/154/1/81

http://microbewiki.kenyon.edu/index.php/Lactobacillus_reuteri

 

[Freddd]

I recently discovered a new probiotic called L. reuteri and after some initial research it seems that it is the only probiotic that seem to be able to produce both folate and cobalamin. I have started taking it a low dose, as I have a couple of stomach isues that I am dealing with. I was wondering if anyone has ever tried it or got any more information on it; and this is a stretch, but perhaps there is enough evidence to add it to the methylation protocol as the last article seems to suggest that it might be of benefit to those with b12 problems. Anyway, here are some links to a couple of papers on it:

http://www.mendeley.com/research/vitamin-b12-synthesis-in-lactobacillus-reuteri/

http://mic.sgmjournals.org/cgi/content/abstract/154/1/81

http://microbewiki.kenyon.edu/index.php/Lactobacillus_reuteri

Hi Bluezone,

You need to recognize what you have found here, part of the search for the holy grail. This is a part of a discussion that has been going on since the discovery of b12 with the vegetarians proclaiming from the mountain that at last they can be free of b12 supplements because it can be obtained from a vegetarian diet, thereby proving that vegetarianism isn't a literal dead end evolutionarily. So far in the 50 years or so this has been going on it has never worked out. Here are the reasons. First of all gut bacteria producing b12 are normally below the area in the small intestine from which b12 is normally absorbed. This can make for some really great manure. A study found that fermented manure has even more cobalamins in it than fresh manure. Before modern cleanliness it is suspected that vegetarians got their b12 from manure that wasn't fully cleaned off of food. I would rather get my b12 from a nice steak than a steaming platter of fresh manure or fermented manure. Second, all three of the articles references are very carefully specific in saying "cobalamin" and "b12". There are at least 18, and maybe more, of plant only cobalamins. These don't work in animals and can't be converted to work in animals by any animal biological process. "B12" by definition is cyanocobalamin. If it was anything usable they would be specifying it to the ceiling.

The limitations of this method are first, it is highly unlikely to produce more than a few mcgs per day of b12, if it produces anything actually usable in a place it can be absorbed and that has to go through the IF keyhole we have spoken about before which isn't enough to heal or reestablish the the methylation cycle. Methylation can be started up, apparently within minutes to hours, with suitable doses of methylb12 and methylfolate and a few other cofactros which may be needed. This can be demonstrated very easily by dropping potassium levels that indicate cell reproduction is occurring which indicates that the DNA transactions are occurring. Further, various epithelial tissues can demonstrate healing starting within days. Why struggle indefinitely with trying to get methylation started?

With adenosylb12. methylb12, methylfolate, l-carnitine fumarate and a few other cofactors, mitochondrial functioning can be restarted within minutes to days in many cases. Again, it doesn't have to be a long protracted struggle. The one thing a lot of people struggle with is that these fast start-ups are unpleasant and so they stop trying to get them going.

Good luck in your journey to health.

 

[kerrilyn]

Ok, I just had a bad reaction and it's something I've not experienced before. I've been taking Adenosylb12 (1 Country Life tab) sublingually in the morning and then 1 B-Right and a 1/4 tab Folapro together in the evening and then 1/2 a Methylb12 tab sublingually shortly after that, before bed. Somedays I forget to take the Methylb12 and there have been days I've not taken any of the pills. Today I forgot to take the Adb12 in the morning so I put it and the Methylb12 under my tongue at the same time. Apparently that was a huge mistake.

Before the Methylb12 had completely dissolved I started to have a reaction. The skin on my arms (from the shoulders down to the hands) and the skin on the front of my knees started to burn, turn red and itch intensely. It felt like my skin was on fire. It happened to a lesser degree on my face too but nowhere else on my body. Besides the red patches, the skin had a goosebump appearance but not welts like hives. I had to apply cold water to take some the burning/itchiness away. This isn't just simple flushing is it? Does flushing itch/burn to that degree?

My skin is still red/blotchy with goosebumps but the burning and itching has started to subside so hopefully it will go away completely soon. Anyway else ever taken Methyl and Adb12 together and have a similar reaction? Any idea why it happened?

I've been pretty tired all day and my heart feels like it's been fluttering in my chest because I've really been overdoing it lately. This evening, before I took the pills, I was experiencing some lightheadedness/dizziness, again probably from overdoing it. I still don't feel great after this rash episode but can't say I feel worse than I did earlier, perhaps a bit more lightheaded.

 

[Freddd]

Ok, I just had a bad reaction and it's something I've not experienced before. I've been taking Adenosylb12 (1 Country Life tab) sublingually in the morning and then 1 B-Right and a 1/4 tab Folapro together in the evening and then 1/2 a Methylb12 tab sublingually shortly after that, before bed. Somedays I forget to take the Methylb12 and there have been days I've not taken any of the pills. Today I forgot to take the Adb12 in the morning so I put it and the Methylb12 under my tongue at the same time. Apparently that was a huge mistake.

Before the Methylb12 had completely dissolved I started to have a reaction. The skin on my arms (from the shoulders down to the hands) and the skin on the front of my knees started to burn, turn red and itch intensely. It felt like my skin was on fire. It happened to a lesser degree on my face too but nowhere else on my body. Besides the red patches, the skin had a goosebump appearance but not welts like hives. I had to apply cold water to take some the burning/itchiness away. This isn't just simple flushing is it? Does flushing itch/burn to that degree?

My skin is still red/blotchy with goosebumps but the burning and itching has started to subside so hopefully it will go away completely soon. Anyway else ever taken Methyl and Adb12 together and have a similar reaction? Any idea why it happened?

I've been pretty tired all day and my heart feels like it's been fluttering in my chest because I've really been overdoing it lately. This evening, before I took the pills, I was experiencing some lightheadedness/dizziness, again probably from overdoing it. I still don't feel great after this rash episode but can't say I feel worse than I did earlier, perhaps a bit more lightheaded.

Hi Kerrilyn,

Hmmmm. Very puzzling. I sincerely doubt that it is from taking adb12 and mb12 at the same time as that is commonly and frequently done by myself and others. The rash doesn't give m any ideas.

I guess the question is is it repeatable?

 

[kerrilyn]

Hi Kerrilyn,

Hmmmm. Very puzzling. I sincerely doubt that it is from taking adb12 and mb12 at the same time as that is commonly and frequently done by myself and others. The rash doesn't give m any ideas.

I guess the question is is it repeatable?

I really didn't want to replicate it because it's pretty unpleasant, but the same reaction happened again tonight. I didn't take the pills over the weekend, or at least didn't take any mb12 and only started them again today. I took the adb12 around 5pm, the B-Right and 1/4 folapro around 9pm and the mb12 at 9:45pm. Only a 1/4 tab of m12 tonight. Before it was completely dissolved under my tongue my face felt odd (tingly) and then very rapidly my knees and arms were burning, red and itchy again.

Now it's happened twice and the common factor has been while the mb12 is in my mouth. I've taken a whole tab previously and didn't have this reaction before. When I took the adb12 tonight I thought it made me feel odd too, can't really explain the feeling but it didn't cause the itchy/redness. I take Melatonin not long after or before taking the mb12, but have been doing that for a while now as well. Also been taking potassium, zinc, vit D, E, C in the mornings.

I thought I've seen some people talking about rashes in this thread, but can't find the posts now. This is not a reaction I want to keep having to this degree anyway.

 

[Freddd]

I really didn't want to replicate it because it's pretty unpleasant, but the same reaction happened again tonight. I didn't take the pills over the weekend, or at least didn't take any mb12 and only started them again today. I took the adb12 around 5pm, the B-Right and 1/4 folapro around 9pm and the mb12 at 9:45pm. Only a 1/4 tab of m12 tonight. Before it was completely dissolved under my tongue my face felt odd (tingly) and then very rapidly my knees and arms were burning, red and itchy again.

Now it's happened twice and the common factor has been while the mb12 is in my mouth. I've taken a whole tab previously and didn't have this reaction before. When I took the adb12 tonight I thought it made me feel odd too, can't really explain the feeling but it didn't cause the itchy/redness. I take Melatonin not long after or before taking the mb12, but have been doing that for a while now as well. Also been taking potassium, zinc, vit D, E, C in the mornings.

I thought I've seen some people talking about rashes in this thread, but can't find the posts now. This is not a reaction I want to keep having to this degree anyway.

Hi Kerrilyn,

You have identified the item, which is a good start. Would you please identify brand and size of mb12? That does not sound like any kind of mb12 reaction or any b12 reaction for that matter that I have ever heard of. It could be a reaction to one of the other ingredients. I would suggest trying Enzymatic Therapy if it was Jarrow or one of the Jarrow sizes if it was Enzymatic therapy or either if it was a different brand. Check the ingredients list.

The "rashes" talked about in relation to b12 is usually related to hydroxycobalamin and is typically an acne like lesion, or several of them erupting after several days of being itchy bumps under the skin, usually starting on the scalp and spreading to the face and lasting until methylb12 is started or weeks have passed without either hycbl or broken down mb12 (=hycbl). If it goes on longer it can spread to the chest and other parts of the body.

I'll see what else I can find. You keep lookimg as well and try another brand. Good luck.

 

[kerrilyn]

Hi Kerrilyn,

You have identified the item, which is a good start. Would you please identify brand and size of mb12? That does not sound like any kind of mb12 reaction or any b12 reaction for that matter that I have ever heard of. It could be a reaction to one of the other ingredients. I would suggest trying Enzymatic Therapy if it was Jarrow or one of the Jarrow sizes if it was Enzymatic therapy or either if it was a different brand. Check the ingredients list.

I'll see what else I can find. You keep lookimg as well and try another brand. Good luck.

Thanks Freddd, I've been using the Jarrow 1000 mcg. Down to a 1/4 tab is only 250 mcg + the 100 mcg in the Jarrow B-Right. I'll try a different brand and see if the issue continues. It will probably take me awhile for me the Enzymatic Therapy mailed here, is it wise to continue with (Country Life) Adb12 on it's own with the B-Right? I took the Adb12 for quite a long time before taking the Methyl over the summer and it seemed to improve my energy and pain levels significantly.

I saw in another thread you mentioned about Adb12 and 2 reactions and only one is felt quickly, compared to approx 600 reactions for Mb12, I was just wondering what those reactions are with Adb12?

 

[kerrilyn]

From what I've been reading this reaction seems similar to a niacin flush, but that doesn't make sense to me if it happens in relationship to taking Methylb12 and not niacin. I also read that you should not drink hot beverages around the time you take niacin because that may increase the likelihood of flushing. Both times I had a reaction I laid down with a heating pad on my lower back. I wonder if that could have any significance as well? Also curious about the role of toxin release and histamine response if this isn't a reaction to the other ingredients.

 

[Freddd]

Thanks Freddd, I've been using the Jarrow 1000 mcg. Down to a 1/4 tab is only 250 mcg + the 100 mcg in the Jarrow B-Right. I'll try a different brand and see if the issue continues. It will probably take me awhile for me the Enzymatic Therapy mailed here, is it wise to continue with (Country Life) Adb12 on it's own with the B-Right? I took the Adb12 for quite a long time before taking the Methyl over the summer and it seemed to improve my energy and pain levels significantly.

I saw in another thread you mentioned about Adb12 and 2 reactions and only one is felt quickly, compared to approx 600 reactions for Mb12, I was just wondering what those reactions are with Adb12?

From what I've been reading this reaction seems similar to a niacin flush, but that doesn't make sense to me if it happens in relationship to taking Methylb12 and not niacin. I also read that you should not drink hot beverages around the time you take niacin because that may increase the likelihood of flushing. Both times I had a reaction I laid down with a heating pad on my lower back. I wonder if that could have any significance as well? Also curious about the role of toxin release and histamine response if this isn't a reaction to the other ingredients.

Hi Kerrilyn,

From what I've been reading this reaction seems similar to a niacin flush, but that doesn't make sense to me if it happens in relationship to taking Methylb12 and not niacin.

That is what my thoughts were at first flush, and that it doesn't make sense.

Also curious about the role of toxin release and histamine response if this isn't a reaction to the other ingredients


2 reactions and only one is felt quickly, compared to approx 600 reactions for Mb12, I was just wondering what those reactions are with Adb12?

Adb12 is immediately and directly involved in the production of ATP in the mitochondria. It is at the heart of energy generation. It can spread into the muscles starting within a few minutes of starting the tablet and continues for some hours afterward, as long as the diffusion gradient is enough. It can also enter the neurons of the brain and cord, though this can take about a 2 hour minimum and is increased by substantially larger doses. Again this is most felt as "energized" but also can have a substantial effect on mood and quieting multisensory hallucinations. The other effect is that adb12 is involved in schwann cell formation of myelin. This takes longer to have any noticeable effect and then that effect is of healing nerves and mb12, omega3 oils and other cofactors are needed.

Let's examine what mb12 does and how fast or slow it does things.

1 -60 minutes:
Mb12 combines with cyanide in the blood forming cyanocobalamin that is rapidly flushed out of the body. Mb12 rapidly combines with (excess?) glutathione forming glutathionylcobalamin that is rapidly flushed from the body. Mb12 starts neutralizing Botox. Mb12 starts neutralizing tetanus toxin. Mb12 starts neutralizing nitroprusside and protecting neurons from glutamate toxicity, protecting neurons from the factors that cause cascading neuron death, combining with nitrous oxide flushing it from the body and increasing neuron speed and signal strength. Autonomic nerves are affected too, possibly dilating blood vessels.

1-10 Days:
Cell formation picks up speed, including immune system cells often depleting serum potassium to sometimes dangerous levels from about the 3rd day onwards. By ten days inflamed tissues are healing, especially epithelial tissues and blood, inflammation is declining, CRP is declining. Bacteria and such start being killed in this period and can start releasing toxins. The effect is not large and doesn't normally cause a massive sudden reaction typical of a Herxheimer reaction If large amounts are taken and there is deep tissue penetration by diffusion, some mercury might be starting to be methylated, picked up in the blood stream and excreted by the liver.

10 - 365+ Days:

Neurological healing may start to be noticable as increased tingling starts quieting down and more normal feeling starts returning, to small areas at a time, and quite suddenly. There is usually a period of hypersensitivity in those newly returned areas of feeling that fades to normal.


Everything I can find indicates that methylb12 and Metafolin both lower histamine levels.

When I first started mb12 I did have a minor skin reaction over the first few weeks. All the areas of rough irritated skin and also infected follicles and acne type lesions all sort of got pushed up and off by rapid new skin formation underneath and when these areas were shed, there was healthy pink new skin underneath instead of the white dead skin or red irritated skin. When I have folate deficiency and my skin starts deteriorating and then I increase Metafolin, the same thing happens over again.

I just don't know what would cause the appearance of a niacin type reaction unless the b12 is the critical cofactor in the process of that happening. It should be fine to continue the adb12 and b-right. Good luck.

 

[bertiedog]

I have just caught up with this very interesting thread. I definitely have a problem with folate because I had a stillborn baby way back in 1973 that had a neural tube defect. Since I found out about Rich's protocol I have been doing a similar sort of protocol since 2007 using 3 Thornes Basic Nutrients daily as well as lots of other supplements. However I haven't really improved at all and wonder whether its because I haven't been taking enough sublingual B12 (only half a tab of Jarrows 1000 mcg and used to chew it). I also think maybe I haven't been taking enough active folate (about 500 mcg of mixed active folates in the BN).

For those who have been following Fredds advice and have a bad case of ME/CFs are you taking just the 800 mg of Metafolin? I have in the cupboard some Actifolate which I haven't opened and wondered if its worth adding that in until the Metafolin I receive the Metafolin? This would be on top of the 500 mg mixed active folates in my multi from Thorne.

The reason I have come to this conclusion is that I had a massage the other day and within an hour or so I started aching very badly all over. I felt quite ill by the evening and had to take pain killers for it and also had very poor sleep that night. The next day I had a severe migraine with exhaustion. Surely this can only be from an excess of toxins in my body not being moved out? I know I still have excess nickel in my body, its been that way for years and I was mercury poisoned but that level came back to normal a few years ago even though it took around 5 years for that to happen despite lots of chelation as per Cutler.

I also tested positive for XMRV last year (antibodies).

Thanks for any advice.

Pam