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B-12 - The Hidden Story

Messages
66
I am up to and maintaining 30 000 mcg's throughout the day of the methyl B12. My urine is not discolored in the manner referred to here. But I am also taking 3200 mcg's of methylfolate throughout the day as well, and I do take it at the same time as the methyl and ad B12's. So this would mean to me that the timing of these doses for me and the absence of the red tinge to urine, would be my body is absorbing the methyl b12?

Laurie

Yes, it would seem so. Are you taking injections? How many? The peak serum concentration will vary considerably for someone taking 6 lozenges one at a time throughout the day (lower) than an individual who takes two 15 mg injections per day (higher).

The idea is that higher doses at once penetrate further into the body and that a dose of ~7.5mg injectable is able to penetrate the CSF, even if the total amount is the same, the lower more frequent dosages will not have the same depth of effect.

I never saw the red in my urine when I used the lozenges, no matter how many I took...

Velha
 

cigana

Senior Member
Messages
1,095
Location
UK
Cigana,

What you've described is a very common phenomena - once you've gotten the mB12 and methylfolate (and possibly other things in place), your body starts up a whole lot of things it hasn't before. This can and typically does create other deficiencies which can lead to returning to fatigue!

This happened to me in particular with the adB12, I felt great at first and had a lot more energy (this is all in relation to what I was feeling then, great at that time is still a WHOLE lot less great than I feel now!!).

You need to follow Fred's full protocol if you want to avoid deficiencies of other things - basic vitamins and also the mitochondrial co-factors. When one has CFS, they are not producing enough energy - this means an issue with your mito, thus other mito support nutrients (d-ribose, carnitine fumarate, alpha lipoic acid, others) can come into play here.

Fred recommends you have everything in place and feel well prior to dropping things. This is what I did, I also had to play with doses of certain things considerably prior to really starting to feel well. In addition I needed prescription amino acids, so while the protocol is very helpful to a large number of people there is still personalization that comes into play.

Read this link and try the suggestions, don't give up now, the fact that you had such a strong reaction initially shows this is an issue for you...

http://forums.wrongdiagnosis.com/showthread.php?p=191131&posted=1#post191131

Velha

Hi Velha,

Thanks for your reply, it really helps to know that the recovery curve was not linear for others. I sometimes wish we could draw graphs, so we could see how people's conditions improved over time. Thanks also for your link, I am going through all threads in reverse chronological order.

There is no way I'm giving up. Since yesterday I also tried taking: zinc, coQ10, l-carnitine fumarate, B-right, d-ribose, alpha lipoic acid, SAMe and TMG. No effect though. I may try upping to large doses, but I think it might be better to wait till I can have some blood tests, hopefully the methylation panel.

One thing I don't understand, why do a lot of people with B12 deficiency need to keep taking high doses every day? Doesn't that suggest their is some mechanism to either (a) cause B12 to leak back out of cells almost as fast as it is diffused into them or (b) cause B12 to change chemically in the cells so it no longer does its job....in which case shouldn't we focus also on that as being a primary problem??

Cheers,

Cig
 
Messages
27
Improvement

I started methyl b12 (jarrow - 5000 mcg, one per day) about a week ago, and am already noticing a large improvement in my symptoms. My symptoms are strongly neurological (i.e. heavy brain fog, constant "out of it" feeling, anxiety, photosensitivity, etc.), and mb12 is helping so much...

I am hesitant to change anything and do Fredd's full protocol, just because I have been feeling so well lately. Fredd - is there anything wrong with just taking methyl b12 by itself?
 
Messages
9
Freddd and others,

My wife has been following Freddd's protocol for about two months and is up to 50 mg single dose sublingual aB12 in the morning, mB12 at bedtime and oral mFolate each time. I expect she will get a prescription soon for SC injections of mB12.

She has had the serious neurological disease Ataxia for more than 5 years which causes her coordination problems with most voluntary movements including walking, typing, speech and reading. On MRI she has visible damage to the cerebellum. She is mostly wheelchair bound at this time. She also has substantial Parkinsonian tremors in her hands.

We are following almost all of the protocol but dropped SAM-e because of the warnings on the box and have currently suspended TMG temporarily.

She has become aware of her sense of smell in the last week and the noisy breathing she does with sleep apnea has greatly diminished and appears to be going away. The latter was very pronounced (scary) and audible at considerable distance.

Before getting the protocol really started she had one night of moderate serotonin syndrome (serotonin poisoning). She stopped taking her antidepressant (an SSRI) the next day and after a few days most of the symptoms were gone.

In the last week or so she has had a return of fairly mild versions of some of the Serotonin Syndrome symptoms. She gets very sleepy, cannot sit up straight particularly when tired and at night her legs may slowly collapse as if they could not handle her body weight.

I suspect she is producing enough extra serotonin to cause the symptoms. She will probably get a blood test in a week. I know SAM-e is involved in serotonin production (which is why we stopped it and for the moment TMG) but I wonder how directly mB12,aB12,mFolate are involved. I don't know if her symptoms are a sign of healing from a number of starved reactions starting back up that are not properly regulated or some other issue(s).

My primary question is do you think I can directly control her serotonin production by changing the amount of mB12, aB12 or mFolate or should I look at the other supplements in the protocol. Her symptoms are mild but a definite downward step from where she was a couple of months ago.

I am looking for opinions/thoughts as I suspect no one has a definitive answer. She has a serious disease (untreatable according to most doctors) and we are taking a number of experimental steps to try to control it. This protocol is far from the first we have tried.

She does have some peripheral neuropathy in her feet which has improved some but until recently she did not have much in the way of a start up reaction at lower doses.

While I am posting, does anyone know if a regular doctor can order a B12 test on a spinal tap (CSF, not just a blood test) or is this only available to researchers.

Thanks,

CSFbear
 

richvank

Senior Member
Messages
2,732
One thing I don't understand, why do a lot of people with B12 deficiency need to keep taking high doses every day? Doesn't that suggest their is some mechanism to either (a) cause B12 to leak back out of cells almost as fast as it is diffused into them or (b) cause B12 to change chemically in the cells so it no longer does its job....in which case shouldn't we focus also on that as being a primary problem??

Cheers,

Cig

Hi, Cig.

For what it's worth, in my hypothesis for CFS (the Glutathione Depletion--Methylation Cycle Block Hypothesis) B12 is being "hijacked" by reactions with toxins.

It has been found (and published) that glutathione normally protects B12 at an intermediate stage in its metabolism inside the cells, before it is converted to the active forms methylcobalamin and adenosylcobalamin.

Lab testing has shown that glutathione is usually depleted in CFS. In an individual case, one can have this measured by the Health Diagnostics and Research Institute methylation pathways panel. I have seen the results of many reports of this panel from people who have CFS, and most are depleted in glutathione. There is, however, a subset of PWCs who do not have depleted glutathione. In those cases, I suspect that there are polymorphisms in the enzymes that use glutathione: the glutathione peroxidases and/or glutathione transferases. This could produce essentially the same effects as depleted glutathione.

Because glutathione is depleted, it is necessary for people with CFS to take very large dosages of B12 initially, until their glutathione levels are restored.

It is necessary to take both large dosages of B12 and at least RDA levels of one or both of the active folates (folinic acid or 5-methyl tetrahydrofolate, or preferably both) in order to lift the partial methylation cycle block, which will eventually raise glutathione automatically. I think this is the key feature of the methylation protocols, of which there are now several in use, including the one suggested by freddd and the Simplified Treatment Approach that I extracted from the full Yasko protocol, with the help of a CFS patient. (I should note that Dr. Alan Vinitsky's protocol uses folic acid instead of the active forms of folate, but he uses massive doses of it, rather than RDA levels. The other methylation-type protocols all use active forms of folate.)

freddd and a few others on this forum have reported that boosting glutathione or its precursors set them back. I don't understand this in the light of the GD-MCB hypothesis, though freddd has reported that he has an inherited mutation in his B12 processing enzymes, and I think that could account for it in his case. Nevertheless, direct glutathione boosting is not part of the Simplified Treatment Approach. We have found by lab testing that when the methylation cycle is brought back up to normal operation, the glutathione level is automatically restored.

Best regards,

Rich
 

richvank

Senior Member
Messages
2,732
Freddd and others,

My wife has been following Freddd's protocol for about two months and is up to 50 mg single dose sublingual aB12 in the morning, mB12 at bedtime and oral mFolate each time. I expect she will get a prescription soon for SC injections of mB12.

She has had the serious neurological disease Ataxia for more than 5 years which causes her coordination problems with most voluntary movements including walking, typing, speech and reading. On MRI she has visible damage to the cerebellum. She is mostly wheelchair bound at this time. She also has substantial Parkinsonian tremors in her hands.

We are following almost all of the protocol but dropped SAM-e because of the warnings on the box and have currently suspended TMG temporarily.

She has become aware of her sense of smell in the last week and the noisy breathing she does with sleep apnea has greatly diminished and appears to be going away. The latter was very pronounced (scary) and audible at considerable distance.

Before getting the protocol really started she had one night of moderate serotonin syndrome (serotonin poisoning). She stopped taking her antidepressant (an SSRI) the next day and after a few days most of the symptoms were gone.

In the last week or so she has had a return of fairly mild versions of some of the Serotonin Syndrome symptoms. She gets very sleepy, cannot sit up straight particularly when tired and at night her legs may slowly collapse as if they could not handle her body weight.

I suspect she is producing enough extra serotonin to cause the symptoms. She will probably get a blood test in a week. I know SAM-e is involved in serotonin production (which is why we stopped it and for the moment TMG) but I wonder how directly mB12,aB12,mFolate are involved. I don't know if her symptoms are a sign of healing from a number of starved reactions starting back up that are not properly regulated or some other issue(s).

My primary question is do you think I can directly control her serotonin production by changing the amount of mB12, aB12 or mFolate or should I look at the other supplements in the protocol. Her symptoms are mild but a definite downward step from where she was a couple of months ago.

I am looking for opinions/thoughts as I suspect no one has a definitive answer. She has a serious disease (untreatable according to most doctors) and we are taking a number of experimental steps to try to control it. This protocol is far from the first we have tried.

She does have some peripheral neuropathy in her feet which has improved some but until recently she did not have much in the way of a start up reaction at lower doses.

While I am posting, does anyone know if a regular doctor can order a B12 test on a spinal tap (CSF, not just a blood test) or is this only available to researchers.

Thanks,

CSFbear

Hi, CFSbear.

I'm sorry to hear about your wife's situation. I don't know much about Ataxia.

It might be helpful to run a Health Diagnostics and Research Institute methylation pathways panel on her to see what the status is of her methylation cycle, her folate metabolism, and her glutathione. Contact info for that is below.

It's true that the methylation cycle (including via SAMe) has major impact on the levels of the neurotransmitters, including serotonin. Some of this occurs by direct methylation reactions, such as in the conversion of serotonin to melatonin, and some occurs via the folate metabolism because of its link to the biopterin cycle. Tetrahydrobiopterin is necessary in the synthesis of both serotonin and dopamine from their precursor amino acids.

I think you are probably correct in thinking that her body has been able to produce more serotonin as a result of being on freddd's protocol. Hopefully, that is a good thing, but it may take some time to get things into proper balance (assuming that is possible in a case of Ataxia, which as I mentioned, I don't know much about).

I might note that the other B vitamins (especially B2 and B6) are also very important in the metabolism of the neurotransmitters, both in their synthesis and in their breakdown, so that if she has also been taking B2 and B6, that could also be affecting her serotonin levels.

I hope this is helpful.

Best regards,

Rich


Methylation Pathways Panel

This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinician’s letterhead.


Available from:

Health Diagnostics and Research Institute
540 Bordentown Avenue, Suite 4930
South Amboy, NJ 08879
USA
Phone: (732) 721-1234
Fax: (732) 525-3288

Lab Director: Elizabeth Valentine, M.D.

Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone.
 

*GG*

senior member
Messages
6,389
Location
Concord, NH
Freddd and others,

My wife has been following Freddd's protocol for about two months and is up to 50 mg single dose sublingual aB12 in the morning, mB12 at bedtime and oral mFolate each time. I expect she will get a prescription soon for SC injections of mB12.

She has had the serious neurological disease Ataxia for more than 5 years which causes her coordination problems with most voluntary movements including walking, typing, speech and reading. On MRI she has visible damage to the cerebellum. She is mostly wheelchair bound at this time. She also has substantial Parkinsonian tremors in her hands.

We are following almost all of the protocol but dropped SAM-e because of the warnings on the box and have currently suspended TMG temporarily.

She has become aware of her sense of smell in the last week and the noisy breathing she does with sleep apnea has greatly diminished and appears to be going away. The latter was very pronounced (scary) and audible at considerable distance.

Before getting the protocol really started she had one night of moderate serotonin syndrome (serotonin poisoning). She stopped taking her antidepressant (an SSRI) the next day and after a few days most of the symptoms were gone.

In the last week or so she has had a return of fairly mild versions of some of the Serotonin Syndrome symptoms. She gets very sleepy, cannot sit up straight particularly when tired and at night her legs may slowly collapse as if they could not handle her body weight.

I suspect she is producing enough extra serotonin to cause the symptoms. She will probably get a blood test in a week. I know SAM-e is involved in serotonin production (which is why we stopped it and for the moment TMG) but I wonder how directly mB12,aB12,mFolate are involved. I don't know if her symptoms are a sign of healing from a number of starved reactions starting back up that are not properly regulated or some other issue(s).

My primary question is do you think I can directly control her serotonin production by changing the amount of mB12, aB12 or mFolate or should I look at the other supplements in the protocol. Her symptoms are mild but a definite downward step from where she was a couple of months ago.

I am looking for opinions/thoughts as I suspect no one has a definitive answer. She has a serious disease (untreatable according to most doctors) and we are taking a number of experimental steps to try to control it. This protocol is far from the first we have tried.

She does have some peripheral neuropathy in her feet which has improved some but until recently she did not have much in the way of a start up reaction at lower doses.

While I am posting, does anyone know if a regular doctor can order a B12 test on a spinal tap (CSF, not just a blood test) or is this only available to researchers.

Thanks,

CSFbear

Have you heard of Low Dose Naltrexone (LDN)?

GG
 
Messages
9
Have you heard of Low Dose Naltrexone (LDN)?

GG

Yes, a number of years ago. It's immunomodulation seemed less well understood than other methods so we gave it a pass at the time. We may revisit in the future but for the moment CNS mB12, aB12 and mFolate seem a far better bet.

Thanks for reminding me though!

CFSBear
 
Messages
9
Hi, CFSbear.

I'm sorry to hear about your wife's situation. I don't know much about Ataxia.

It might be helpful to run a Health Diagnostics and Research Institute methylation pathways panel on her to see what the status is of her methylation cycle, her folate metabolism, and her glutathione. Contact info for that is below.

It's true that the methylation cycle (including via SAMe) has major impact on the levels of the neurotransmitters, including serotonin. Some of this occurs by direct methylation reactions, such as in the conversion of serotonin to melatonin, and some occurs via the folate metabolism because of its link to the biopterin cycle. Tetrahydrobiopterin is necessary in the synthesis of both serotonin and dopamine from their precursor amino acids.

I think you are probably correct in thinking that her body has been able to produce more serotonin as a result of being on freddd's protocol. Hopefully, that is a good thing, but it may take some time to get things into proper balance (assuming that is possible in a case of Ataxia, which as I mentioned, I don't know much about).

I might note that the other B vitamins (especially B2 and B6) are also very important in the metabolism of the neurotransmitters, both in their synthesis and in their breakdown, so that if she has also been taking B2 and B6, that could also be affecting her serotonin levels.

I hope this is helpful.

Best regards,

Rich


Methylation Pathways Panel

This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinicians letterhead.


Available from:

Health Diagnostics and Research Institute
540 Bordentown Avenue, Suite 4930
South Amboy, NJ 08879
USA
Phone: (732) 721-1234
Fax: (732) 525-3288

Lab Director: Elizabeth Valentine, M.D.

Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone.

Hi Richvank,

Sorry I didn't respond sooner, I somehow overlooked your reply. Thank you for the quick reply.

I think there are common problems among the major neurological diseases and B12, folate deficiencies in the brain are among them. I know this site is dedicated to CFS but I think a lot of the methylation cycle applies to others particularly with age or exposure to nitrous oxide or other B12 depleting compounds.

We are using Freddd's protocol as a indirect diagnostic of CSF B12/folate deficiency in my wife until we can find out if there is a way a clinician can test it directly (from a spinal tap). Her prognosis has taking a substantial turn for the worse lately but it is not the symptoms she has had for the last few years, it is new symptoms. She has had a couple of changes that may be signs of CNS healing.

I have been thinking of asking her neurologist to prescribe Deplin (metfolin) and it occurs to me that she has been getting the equivalent amount of metfolin from the Solgar supplement as she would from a higher Deplin dose. For the moment she will stay off mefoline to see if it affects her symptoms in a few days. I expect she will then start back with a lower dose.

I am rather unclear on the ratio of aB12, mB12 and metfolin. I know Freddd is trying to get high enough blood levels for each of the above to diffuse into the brain before the kidneys can remove it. At the blood and at the cellular level, what should be the ratio be of the different forms. At first guess one might assume the same number of moles of each but the body does not seem to be bound by what we consider reasonable assumptions.

One other question, do you know if people have had trouble getting insurance companies to pay for the Methylation Pathways Panel? It is amazing some of the hoops we have had to go through.

Thanks in advance!

CFSbear
 

cigana

Senior Member
Messages
1,095
Location
UK
Hi, Cig.

For what it's worth, in my hypothesis for CFS (the Glutathione Depletion--Methylation Cycle Block Hypothesis) B12 is being "hijacked" by reactions with toxins.

It has been found (and published) that glutathione normally protects B12 at an intermediate stage in its metabolism inside the cells, before it is converted to the active forms methylcobalamin and adenosylcobalamin.

Lab testing has shown that glutathione is usually depleted in CFS. In an individual case, one can have this measured by the Health Diagnostics and Research Institute methylation pathways panel. I have seen the results of many reports of this panel from people who have CFS, and most are depleted in glutathione. There is, however, a subset of PWCs who do not have depleted glutathione. In those cases, I suspect that there are polymorphisms in the enzymes that use glutathione: the glutathione peroxidases and/or glutathione transferases. This could produce essentially the same effects as depleted glutathione.

Because glutathione is depleted, it is necessary for people with CFS to take very large dosages of B12 initially, until their glutathione levels are restored.

It is necessary to take both large dosages of B12 and at least RDA levels of one or both of the active folates (folinic acid or 5-methyl tetrahydrofolate, or preferably both) in order to lift the partial methylation cycle block, which will eventually raise glutathione automatically. I think this is the key feature of the methylation protocols, of which there are now several in use, including the one suggested by freddd and the Simplified Treatment Approach that I extracted from the full Yasko protocol, with the help of a CFS patient. (I should note that Dr. Alan Vinitsky's protocol uses folic acid instead of the active forms of folate, but he uses massive doses of it, rather than RDA levels. The other methylation-type protocols all use active forms of folate.)

freddd and a few others on this forum have reported that boosting glutathione or its precursors set them back. I don't understand this in the light of the GD-MCB hypothesis, though freddd has reported that he has an inherited mutation in his B12 processing enzymes, and I think that could account for it in his case. Nevertheless, direct glutathione boosting is not part of the Simplified Treatment Approach. We have found by lab testing that when the methylation cycle is brought back up to normal operation, the glutathione level is automatically restored.

Best regards,

Rich

Hi Rich,

Thanks for your reply, I find your theory fascinating. But what I still don't understand is that Freddd and others like him have to keep supplementing with the active forms of B12 (which from what you've said are not hijacked by the toxins - only the intermediate forms are hijacked). What is it that causes the active forms to be rendered useless or depleted from the cells on a daily timescale, any ideas?

Cheers,

Cig
 

richvank

Senior Member
Messages
2,732
Hi, cig and aquariusgirl.

To the best of my current understanding, all the cobalamin forms except glutathionylcobalamin can be hijacked by toxins. There are still some parts of B12 metabolism that have not been sorted out completely by the researchers in this field, but here's a synopsis of what is believed to be known at this point:

When various forms of B12 are taken orally via food or ordinary oral supplements (not sublingually, transdermally, liposomally or by injection) in a normally operating digestive system, all the forms of B12 are separated from protein by acid in the stomach, and are bound to haptocorrin. In the early part of the small intestine, the haptocorrin is broken down, and the B12 forms are bound to intrinsic factor, which is produced by the parietal cells of the stomach. In the last part of the small intestine (the terminal ileum) there are receptors for intrinsic factor, and it is drawn into the cells lining the intestine (enterocytes), together with the forms of B12 that are bound to it. The enterocytes transfer the B12 forms to transcobalamin, which is carried in the blood to the various cells of the body. The cells have receptors for transcobalamin, and they draw it into lysosomes inside the cells. In the lysosomes, the transcobalamin is broken down, and the forms of B12 are freed. They are passed from the lysosomes into the cytosol, and their beta ligands are removed. These include hydroxo-, methyl-. and adenosyl-. At this point the B12 is just cobalamin. The cobalamin is then passed either to methionine synthase in the cytosol or into the mitochondria. The fraction that is passed to methionine synthase is methylated by SAMe to become methylcobalamin and it supports the methylation cycle. The fraction that passes into the mitochondria is converted to adenosylcobalamin, and it supports methylmalonyl-CoA mutase.

It has been proposed that during its metabolism in the cytosol of the cells, B12 is normally chaperoned by proteins over its entire pathway to formation of the B12 coenzyme forms. There is evidence that glutathione is involved in this chaperoning process, by formation of glutathionylcobalamin, which protects cobalamin from reacting with toxins during its transition from the initial form that was absorbed to its final coenzyme form, either methylcobalamin or adenosylcobalamin. But the details of this process are still not totally elucidated. I have hypothesized that this need for chaperoning is the reason why depletion of glutathione leads to loss of B12 function, and thus a partial block of the methylation cycle as well as a partial block of the methylmalonate reaction, which causes methylmalonate to rise in the urine organic acid tests.

Note that all forms of B12 that are taken by the ordinary oral route are normally treated the same way. Their individual ligands are removed, and then the two coenzyme forms of B12 are produced as needed by the cells. Because of this, the intake form of B12 are all vulnerable to hijacking, if there is not enough glutathione to protect the intermediate cobalamin.

Now, what about taking high dosages of forms of B12 by the artificial routes (sublingual, transdermal, liposomal, or injection)? If the dosages are high compared to usual RDA-type B12 dosages, which are in the few micrograms range, that is, if they are up to several milligrams, 1000 times higher than RDA-type levels, then the capacity of transcobalamin to bind the B12 in the blood will be overwhelmed. The transcobalamin will be saturated, and it will carry its bound B12 to the cells in the normal way. The B12 in excess of this will be carried in the blood in an unbound state. As far as I know, the behavior of this unbound B12 has not been researched, but based on the experiences of many people, it appears that some of it is able to diffuse across cell membranes and enter cells without benefit of the transcobalamin receptors. Whatever does not enter the cells in this way is extracted from the blood by the kidneys and passes into the urine.

Again, the behavior of unbound B12 forms after they diffuse into the cytosol of the cells has not been researched. However, based on experiences reported, at least some of both methylcobalamin and adenosylcobalamin appear to be able to perform their normal coenzyme functions after entering the cells in this manner. If the dosages are high enough, they can apparently overwhelm the hijacking by toxins sufficiently so that some survives to perform their normal functions. In the case of hydroxocobalamin given by these artificial routes, some apparently enters the cells, and it must be converted to methylcobalamin and adenosylcobalamin inside the cells, even though it did not come in via the transcobalamin mechanism, because the experimental evidence is that it does support the normal coenzyme functions of B12.

If a person has normal cobalamin processing enzymes in their cells, it seems to me that after sufficient detoxication has taken place and glutathione levels have been restored, the hijacking of B12 by toxins will decrease, and the amount of B12 supplementation needed should also decrease. It may take considerable time to get the toxin load down, though, especially if the person has been ill for a long time, and the toxins have built up considerably while the detox system was dysfunctional.

On the other hand, there are people who have genetic mutations in one or more of the intracellular B12 processing enzymes. These are called inborn errors of metabolism. In these cases, the cells may not be able to utilize B12 and make its own coenzyme forms in the normal way. If this is the situation, then the person may have to continue to take high-dosage B12, either methylcobalamin or adenosylcobalamin or both, depending on the mutations present. freddd has reported that this is his situation. Based on his experience that taking glutathione or its precursors caused a major setback in his B12 function, it would seem that his inborn error of metabolism must involve a step downstream of the formation of glutathionylcobalamin. Apparently, once glutathione combines with cobalamin, his cells are not able to use it to make the coenzyme forms. I don't think this is the situation with most people who have ME/CFS. Therefore, I think that with time, most will be able to drop back on their B12 dosages. There are a small number who have reported what appears to be complete recovery, and as far as I know, they haven't continued taking high dosages of B12, but I don't really have much data on this. I would very much appreciate hearing from people about their experiences with this.

I should also note that there are people who have various other problems in B12 handling. Some have low stomach acid, so that they are not able to liberate B12 from protein in the stomach. Some have pernicious anemia, so that they don't have enough intrinsic factor, and thus can't absorb B12 from the gut. Some have had an intestinal disease such as Crohn's or celiac, or they have had part of their intestine removed surgically, so they also cannot absorb B12 well from the gut. Some have a transcobalamin deficiency, so that they can't bind B12 and transport it properly in the blood. Some may lack transcobalamin receptors on their cells, and so on.

Just for completeness, let me note that the cells apparently export extra B12 that they don't need back to the blood, bound to haptocorrin. This actually constitutes most of the B12 that is normally found in the blood at any time. This B12 is eventually imported by the liver. Some is stored in the liver, and some is excreted in the bile, passing back to the intestine, where is again available to be bound to intrinsic factor and reabsorbed. This part of the B12 metabolism has not been completely researched, but apparently it is a salvage pathway that avoids wasting B12 and provides it at times when not much is coming in from the diet.

Best regards,

Rich
 

maryb

iherb code TAK122
Messages
3,602
Location
UK
Rich I tried the methylation program briefly) but gave up as I felt too ill (even on a fraction of the dose) and decided to wait until I had my mercury fillings out.
I have been injecting cynacobalamin and magnesium for a few years now and always felt better whilst on them.
I changed to hyroxycobalamin a few weeks ago and have gone downhill, I also started taking Lipospheric Vit C at the same time, do you think there could be a link?
I am due to go to the dentist to start mercury removals tomorrow and feel utterly rubbish.
I would really value your opinion.
 

richvank

Senior Member
Messages
2,732
Hi, maryb.

I'm sorry that you are feeling so badly and that the methylation treatment was not tolerable for you.

I don't understand how a switch from cyano- to hydroxo-cobalamin in itself would have caused you to go downhill, since if anything, the cyano- would have been putting some cyanide into your body, which the hydroxo- would not. Generally speaking, I don't think cyano-cobalamin is the best choice when milligrams level dosages are being given, because, though many people's bodies can deal with the cyanide alright, I have encountered one case in which this was very detrimental.

I don't have experience with hydroxocobalamin treatment combined with liposomal vitamin C, so I don't know whether that combination could have been responsible for your downturn.

On the amalgam removal, I think the best approach is to do it gradually, rather than having several amalgams removed on the same day. Also, I think it is best if the dentist uses a high flow of cooling water to keep the temperature (and hence the vapor pressure) of the mercury low during the procedure, and also gives the patient an external air supply to breathe, so as to avoid inhaling mercury vapor to the degree possible. I think that the main mercury exposure to the patient during this procedure is inhalation of vapor, rather than swallowing of solid pieces.

I wish I knew the best procedure overall to deal with amalgams. As you probably know, this is a controversial topic, and I don't think that controlled studies have been done to determine how best to proceed. I have read reports from several people who found that they experienced difficulty after having amalgams removed (presumably from mercury exposure), especially if many were removed at once, and the above precautions were not taken. Some argue that detoxing should not be done until after amalgams are removed, based on the general principle in toxicology that the source of the toxin should first be eliminated. The difficulty with amalgams is that removing the source of the toxin also entails giving the patient an acute exposure to mercury, especially if the above precautions are not taken.

Some people have left their amalgams in until after their detox system has had a chance to come back up and be functioning more normally, and I've read reports from some that this has worked O.K. for them.

These are all anecdotal reports, so it is difficult to reach a clear conclusion from them, and that is unfortunately the status of this issue, as far as I know.

I wish you success with the amalgam removal and subsequent treatment.

Best regards,

Rich
 

maryb

iherb code TAK122
Messages
3,602
Location
UK
Rich thank you for taking the time to reply, you really are so kind. I was hoping you would say that about the B12 and Vit C.
I had 2 amalgams out today and re-filled. The dentist is one of the few in the UK who does the specialised procedure as you outlined above. It was still very stressful though but hopefully if I can maintain it over the next 6 weeks they will all be gone, whether they are having any effect on my health I don't know, but they're like an itch I have to scratch:) take care and thanks once again.
 

kday

Senior Member
Messages
369
Rich,

I was previously taking large doses of B12 to make it through the day. And by large doses I mean talking 25 mg/ml of methylcobalamin IM.

It's been 4 or 5 months perhaps (I haven't been counting), and I now have continuous detox and don't feel the "B12 cravings" that I used to.

This was correlated by a detox I did that was created by William Lee Cowden. I know it sounds nuts, but it was it was a laser energetic detox using homeopathic nosodes.

Correlation vs. Causation: I can't say for sure that this detox is what turned my methylation status around, but it was heavily correlated.

Shortly after the detox, I no longer felt the need for the B12 shots. I also watched the lunulae on my fingers come back large and white. While I only have large lunulae on my thumbs, very small lunulae have appeared on my index on middle finger. Before doing a methylation protocol, I had no lunulae on any fingers (including thumbs). However, according to American standards, my B12 was "normal" (somewhere in the 300s I think).

While I did notice I had an absence of lunulae before the methylation protocol, I do not recall what they looked like or how many there were when I was in my healthy state.

I have tested positive for HPU via Vitamin Diagnostics, and I have low Zinc, so it may be the next thing I pursue.

In terms of methylation panels, I never did one. They were expensive, and I honestly didn't the point of throwing out money when I knew my protocol was working. I didn't keep track of my glutathione status or anything like that, but I'm sure if I did, it seems quite obvious that the papers would show improvement.

In terms of effectiveness, the methylating supplements I took were what I would call highly effective. It calmed me more than benzodiazepine drugs, and as long as I did my injection and supplements, I could tolerate something like loud wedding reception with a band playing. To illustrate the severity, if I didn't take the supplements, simply riding in a car was too overstimulating and would cause anxiety, overstimulation, and even panic attacks. While I was on them, I would compare it to an addiction. My body needed and craved the supplements. It was hard to go a day or two without. When I did my HPU test, I had to go five days without it, and I didn't feel like I could survive those 5 days.

Low doses and sublinguals did absolutely nothing for me. Perhaps this was the hijacking of toxins. As I've said in other threads I have had very obscure detox symptoms, and I can't find anyone that relates to me. I'm not sure why this is the case, but I consider my case somewhat unique in this sense.

When the floodgates opened, I was actually having urinary retention. I figured out on my own that I had to drink 1.5 liters at a time. You think this would cause dilute clear urine, but it was quite the opposite. Even though the releasing of whatever this is makes me feel better, it was so strange to me that I kept seeking tests of my kidney and liver function along with several laboratory performed UAs. I also bought an at-home kit because of my concern.

Now these symptoms I am speaking of are diminishing. I still think my kidneys and liver filter much more than your average Joe, but it's slowing and I am not experiencing the urinary retention like before.

Am I recovered? No. Do I feel a lot better? Yes. I was what a CFS scale would/ call severely ill and completely non-functional, so I think recovery will continue to be slow. I think damage has been done, and hopefully time can take care of it. I do feel like I am on a slow uphill climb. I don't know how far up the hill I will get, but I am hoping for wellness and do think it is possible.

I don't think I am experiencing the typical relapsing/remitting patterns you commonly hear about. I think there is too much clinical/objective evidence in my favor to draw such a conclusion.

I am on antibiotics and herbal antibiotics. I tried stopping antibiotics for about a month against my doctor's advice, and while I felt better than ever for about 3 weeks, it was obvious that I needed to go back to them. I am not one that likes taking antibiotics (I literally never took them in my life before I got ill), but I also learned through this journey that I must listen to my body.

Thanks Rich for your research and support (and everyone else). I am not doing a methylation protocol as of now, but I have been considering restarting it at lower dosages. However, I no longer feel the pharmacological-like effects like before, and it's hard for me to stick to things when I don't feel much.

-Kyle
 

richvank

Senior Member
Messages
2,732
Hi, Kyle.

Thanks for reporting your experience. I'm glad you have figured out some things that have been helpful for you, and I hope that your improvement will continue to a complete recovery.

I know Dr. Cowden and have seen him demonstrate his treatment. I can't say that I understand how it works on a basic scientific level, but I have confidence in him, and I have also heard of good results from others. I'm glad his treatment has helped you to detox. What toxins did he identify in your body with the Zyto machine? (I presume he used that in your case.)

I've read various discussions of the lunulae, but I don't understand what causes them to disappear and to reappear. Are you suggesting that B12 is involved?

The positive HPU test could well be a clue to what is going on in your case. As you noted, it would be consistent with low zinc, and zinc is very important for the operation of the methylation cycle. Dr. Klinghardt has made the point that HPU will block the methylation cycle as well as the transsulfuration pathway, because of the drop in zinc and B6, in particular.

I appreciate knowing that the sublingual B12 didn't help you. It does sound as though you needed higher dosages, and methylcobalamin rather than hydroxocobalamin. There seems to be a wide difference between different people in terms of what they need to boost their methylation, and how they tolerate the various protocols. I'm glad you persisted and found out what worked in your case.

The urinary retention you experienced is also unusual, at least in my experience. More commonly, people report diabetes insipidus symptoms, involving high daily urine volumes combined with more or less continuous thirst, in M.E./CFS.

The need for antibiotics seems to suggest that you have one or more bacterial infections. I'd be interested to know which antibiotics you are using, and in particular if they ones that are effective against intracellular bacteria, since those seem to be the dominant types in M.E./CFS.

You're certainly welcome for whatever I have been able to contribute to helping you regain your health. Thank you for sharing the path you have taken. I learn a great deal from knowing what actually works or doesn't work for people.

Best regards,

Rich
 
Messages
8
Great thread, I have read the whole thing in the last two weeks and have learned alot. Hopefully I can add to it as well. A little about me, I had 11 amalgams put in my mouth in 2004 as well as being exposed to toxic mold at work during the same time. In 2005, at 32 I was suffering dementia, chronic fatigue, auditory hallucinations, massive candida infestation etc. I am 90% better today as is my wife who went through the mold with me since we worked at the same place. We did it ourselves! At one point, the month of auditory hallucinations, I wanted to end it all every second of every day. Turns out that massive amounts of NAC with amalgams in my mouth was a bad idea from another bad doc! One doctor out of many ran some tests that showed me the way but I could not afford him since we were living off of credit and out of work for months. We slowly recovered, got my amalgams all out in 07/08 and moved to Vegas from FL to get away from the mold in 08.

We would both like more energy, our jobs are from physically strenuous to unbelievably strenuous (working in the desert installing solar in the middle of the summer).

We are taking MB12 injections (1mg a day). Jarrow MB12 5mg (1) a day.Source Naturals(SN) Dibencozide 10-22mgs a day, it is also in our B Complex. (SN) Coenzymate B Complex 2-4 a day.(SN) Coenzymated B-6 25-100mgs a day. Also taking (SN) Megafolinic and VRP Active Folate. Just received NSI Carnitine Fumarate, Enzymatic Therapy Krebs Cycle Chelates and (SN) Advanced Ferrochel (IRON). The Iron gave me tons of energy along with my wife, we took it first before the carnitine and Chelates. 30% of the world is iron deficient especially women. Look up Iron deficiency symptoms, Ferrrochel is probably the safest iron. Also, all of our Source Natural products are sublingual besides the Ferrochel and the Alpha Lipoic and Enzymes. The sublingual Coenzymated B Complex is UNBELIEVABLE!! Another supplement that is Outstanding is Peter Gillams Magnesium Drink Natural Calm. Only thing that come close to that is drinking Epsom salts! Of course we take all the Basics as well.

Some things I know about our protocol. It moves mercury for sure. I have used DMSA to get rid of brain fog several times so far from this protocol. I used it alot after I got my amalgams out.

TMG (betaine) slows down methylation, it depends on how much TMG you convert to DMG. DMG adds to methylation as I see it. N-Acetyl Cysteine really slows down methylation. Adding it not only frees up mercury (I know due to auditory hallucinations in the past) but it also slows down the folate cycle which adds to the Methylation Cycle.

I know FREDD had problems when he added NAC in the past and Ibelieve I understand why. NAC slows down methylation, but it also pulls mercury out of tissues and half-ass chelates it.Pulling mercury will slow down methylation by stealing methyl groups. I don't believe glutathione would slow down methylation besides the fact of what it will do with mercury just like NAC. Glutathione should not pull out of the Methylation Cycle like NAC though.

Here is a link to the Methylation/Folate Cycles and how they are connected to the Kreb Cycle. There are tons of these cycles on the net and many do not show all that goes on. This one may not but it is a good one.

http://www.google.com/imgres?imgurl...a=X&ei=OhT4TKbVF428sAOxwvGlAg&ved=0CB4Q9QEwAQ