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B-12 - The Hidden Story

richvank

Senior Member
Messages
2,732
Importance of testing methylation cycle

Hi, all.

I just want to note that methyl B12 has only one known function in the human body, which is to serve as a coenzyme for methionine synthase in the methylation cycle. Adenosyl B12 also has only one known function, and it is to serve as a coenzyme for methylmalonyl-CoA mutase. All the effects of vitamin B12 have been found to derive from these two functions.

Normally, the various forms of B12 in the diet or in supplements at RDA-level dosages go through the normal absorption, transport and intracellular processing and are converted to the amounts of these two coenzymes that are needed by the cells.

When very large dosages of methyl B12 compared to RDA levels are taken sublingually or by injection, the normal absorption, transport and processing of vitamin B12 into these two coenzymes are bypassed. Under these conditions, I think it may be possible to get too much methyl B12 into the cells, and that this could overdrive methionine synthase, so that cystathionine beta synthase will not receive sufficient homocysteine to feed the transsulfuration pathway sufficiently for the production of cysteine, glutathione, taurine, sulfate and other sulfur-containing metabolites. In addition, the methylation capacity might rise too high, which could affect DNA methylation and therefore gene expression. I think this is relatively uncharted territory, and going there may produce some deleterious effects.

Therefore, I think it would be wise to do some testing periodically while on high-dose B12 supplementation. The best test panel is the Vitamin Diagnostics methylation pathways panel. Unfortunately, because of a lab move, the availability of this test will probably be hampered until about the end of January. I think the next best would be a plasma amino acids panel, such as is offered by Doctor's Data Lab. The condition of the methylation cycle and the transsulfuration pathway can be inferred from this panel, though the interpretation is not as direct as with the Vitamin Diagnostics panel.

I again want to note that I think that the response to high-dose B12 treatment will differ for those who have inborn errors of metabolism involving the intracellular B12 processing enzymes and those who do not. It is not normal for a person's body not to be able to use hydroxocobalamin, and it is also not normal for glutathione to interfere with the utilization of B12. In fact, its normal role is to protect B12. The presence of these abnormalities suggests that there is an inborn error of metabolism involving the B12 processing enzymes.

In the past, I have noted that the simplified treatment approach, which utilizes hydroxocobalamin, has been found to help at least two-thirds of the people with CFS who have tried it. It is not clear that the treatment failure in the other nearly one-third is due to their inability to utilize hydroxocobalamin, as freddd has suggested. Rather, it looks as though deficiencies in cofactors or in amino acids are responsible in many cases, based on lab test results I've studied so far.

Best regards,

Rich
 

Marylib

Senior Member
Messages
1,155
for Rich

Thanks for your post.

Earlier I had assumed that your reluctance to recommend methyl b12 was due to concerns about mercury.

Am I correct in reading your current post that your concerns about methyl b12 have expanded somewhat?

Thanks.
 

DrD

Messages
45
Hi, all.

I just want to note that methyl B12 has only one known function in the human body, which is to serve as a coenzyme for methionine synthase in the methylation cycle. Adenosyl B12 also has only one known function, and it is to serve as a coenzyme for methylmalonyl-CoA mutase. All the effects of vitamin B12 have been found to derive from these two functions.

Normally, the various forms of B12 in the diet or in supplements at RDA-level dosages go through the normal absorption, transport and intracellular processing and are converted to the amounts of these two coenzymes that are needed by the cells.

When very large dosages of methyl B12 compared to RDA levels are taken sublingually or by injection, the normal absorption, transport and processing of vitamin B12 into these two coenzymes are bypassed. Under these conditions, I think it may be possible to get too much methyl B12 into the cells, and that this could overdrive methionine synthase, so that cystathionine beta synthase will not receive sufficient homocysteine to feed the transsulfuration pathway sufficiently for the production of cysteine, glutathione, taurine, sulfate and other sulfur-containing metabolites. In addition, the methylation capacity might rise too high, which could affect DNA methylation and therefore gene expression. I think this is relatively uncharted territory, and going there may produce some deleterious effects.

Therefore, I think it would be wise to do some testing periodically while on high-dose B12 supplementation. The best test panel is the Vitamin Diagnostics methylation pathways panel. Unfortunately, because of a lab move, the availability of this test will probably be hampered until about the end of January. I think the next best would be a plasma amino acids panel, such as is offered by Doctor's Data Lab. The condition of the methylation cycle and the transsulfuration pathway can be inferred from this panel, though the interpretation is not as direct as with the Vitamin Diagnostics panel.

I again want to note that I think that the response to high-dose B12 treatment will differ for those who have inborn errors of metabolism involving the intracellular B12 processing enzymes and those who do not. It is not normal for a person's body not to be able to use hydroxocobalamin, and it is also not normal for glutathione to interfere with the utilization of B12. In fact, its normal role is to protect B12. The presence of these abnormalities suggests that there is an inborn error of metabolism involving the B12 processing enzymes.

In the past, I have noted that the simplified treatment approach, which utilizes hydroxocobalamin, has been found to help at least two-thirds of the people with CFS who have tried it. It is not clear that the treatment failure in the other nearly one-third is due to their inability to utilize hydroxocobalamin, as freddd has suggested. Rather, it looks as though deficiencies in cofactors or in amino acids are responsible in many cases, based on lab test results I've studied so far.

Best regards,

Rich

hi Rich

"which could affect DNA methylation and therefore gene expression. I think this is relatively uncharted territory, and going there may produce some deleterious effects.



could you indicate which disease states would manifest themselves as a result of these deleterious effects? I assume Cancer, amongst others......
 

richvank

Senior Member
Messages
2,732
To marylib and DrD re: methyl B12

Hi, Marylib and Dr D.

I've expressed two concerns on this board in the past: possible methylation of inorganic mercury and movement of it into the brain, and the high dosages relative to what PWCs can tolerate in the presence of detox.

Another concern, which I've expressed on other boards in the past but perhaps not here, is that I believe that the goal should be to restore the methylation cycle to normal operation, not to overdrive it. This issue has come up several times in connection with concerns about cancer. It is known that methylation is abnormal in cancer cells. The tumor suppressor genes are overmethylated, silencing them, and the oncogenes are undermethylated. I don't think it's understood how this occurs.

There is a mechanism built into cells to limit the ratio of SAMe to SAH in the methylation cycle, involving glycine and sarcosine. I think there must be a reason for the presence of this mechanism, and it is probably intended to prevent overmethylation. My concern is that I suspect that it is possible to override this putative safety mechanism if large enough dosages of methylcobalamin are used.

I think that in order to make sure that the methylation cycle is not being overdriven, it is prudent to run a test periodically to see how it's doing, especially if very high dosages of methyl B12 are being used. I have recommended the same for the Simplified Treatment Approach, which uses a fairly high dosage of hydroxo B12, on other boards.

I just think people should be cautious about this, since I don't think possible effects of overdriving the methylation cycle are well understood.

Rich
 

klutzo

Senior Member
Messages
564
Location
Florida
TMG and LDL

Dear Freddd or Rich,
A few posts back there was a reference to a study which included the info that TMG raised LDL in research subjects.

This is alarming to me because my LDL is already high due to Lyme Disease, and I am tired of my Lyme-ignorant doctors giving me a hard time about it. They don't realize that the body raises LDL in Lyme patients because it can remove endotoxins from the blood, and they won't believe me when I tell them this, since I am just a dumb patient. I sure don't want my LDL going even higher and end up having to explain once again why I can't/won't take statin drugs.

I have taken 500 mgs. TMG from the very first day I started this protocol. I have zero reaction to it, just like I had zero reaction to SAMe. If I remember what I read correctly, 100 mgs. TMG was enough to raise LDL and it was recommended not to take more than that if taking B vitamins....I believe that comment was from Dr. Sahelian, who is quite cautious about dosing (I've been getting his newsletter for years).

I have labs done one month from now. Do you think I need TMG when I do not react to it?

klutzo
 
I

imgeha

Guest
I've expressed two concerns on this board in the past: possible methylation of inorganic mercury and movement of it into the brain, and the high dosages relative to what PWCs can tolerate in the presence of detox.

Another concern, which I've expressed on other boards in the past but perhaps not here, is that I believe that the goal should be to restore the methylation cycle to normal operation, not to overdrive it. This issue has come up several times in connection with concerns about cancer. It is known that methylation is abnormal in cancer cells. The tumor suppressor genes are overmethylated, silencing them, and the oncogenes are undermethylated. I don't think it's understood how this occurs.

There is a mechanism built into cells to limit the ratio of SAMe to SAH in the methylation cycle, involving glycine and sarcosine. I think there must be a reason for the presence of this mechanism, and it is probably intended to prevent overmethylation. My concern is that I suspect that it is possible to override this putative safety mechanism if large enough dosages of methylcobalamin are used.

I think that in order to make sure that the methylation cycle is not being overdriven, it is prudent to run a test periodically to see how it's doing, especially if very high dosages of methyl B12 are being used. I have recommended the same for the Simplified Treatment Approach, which uses a fairly high dosage of hydroxo B12, on other boards.

I just think people should be cautious about this, since I don't think possible effects of overdriving the methylation cycle are well understood.

Rich

Hi Rich

What doses of the methylfolate and mB12 would you say would NOT overdrive the methylation cycle? I know that the RDA for B12 is actually very low, but is genetic testing the only way to estimate how much we individually need? I understood that excess B12 is filtered out by the kidneys and urine, so how could too much enter the cells?

thanks

Nicola
 

richvank

Senior Member
Messages
2,732
Dosages

Hi Rich

What doses of the methylfolate and mB12 would you say would NOT overdrive the methylation cycle? I know that the RDA for B12 is actually very low, but is genetic testing the only way to estimate how much we individually need? I understood that excess B12 is filtered out by the kidneys and urine, so how could too much enter the cells?

thanks

Nicola

Hi, Nicola.

I think that the dosages that will not overdrive the methylation cycle probably vary from one person to another, because we have different sets of polymorphisms in the genes that code for enzymes in the methylation cycle and the related pathways. That's why I recommend periodic testing.

As you know, the Simplified Treatment Approach uses hydroxocobalamin rather than methylcobalamin. I realize that freddd has not found this to be helpful in his case, and reportedly in some others. However, it does seem to work for most people who have CFS, and who apparently do not have inborn errors of metabolism in the genes that code for the intracellular B12 processing enzymes. An advantage of using hydroxocobalamin is that it must be converted to methylcobalamin by these enzymes before it can be used to support methionine synthase in the methylation cycle. These enzymes can therefore control this conversion, so that the methylation cycle will not be overdriven.

It is probably true that some people need the methylcobalamin form, either because of a serious lack of methylation capacity to convert hydroxocobalamin into methylcobalamin, or because they have a genetic problem with the processing enzymes, as freddd appears to have, based on what he has reported.

In the case of low methylation capacity, a small amount of TMG would be another thing to try, because it stimulates the BHMT alternate pathway from homocysteine to methionine in the liver and kidneys, and this can help to produce more SAMe, and thus higher methylation capacity. Thus, the BHMT pathway can be used to "bootstrap" the methionine synthase pathway. However, too high a TMG dosage may cause the BHMT pathway to dominate, so that the methionine synthase pathway will not come up. This is a problem, because they are not interchangeable. It's necessary to get the methionine synthase pathway running because it impacts the folate metabolism, too, and that is necessary to make new DNA and RNA as well as to process Figlu to form glutamate. There is a small amount of TMG in the multi that is part of the Simplified treatment.

Taking some SAMe directly is another way to lift the methylation capacity in order to facilitate the conversion of hydroxocobalamin to methylcobalamin.
Some people do well with this, and others don't tolerate it well, perhaps because their sulfite oxidase enzyme is not able to handle the processing of the additional sulfur metabolites that come from metabolism of SAMe. Sometimes molybdenum will help with this, because it forms a cofactor for sulfite oxidase.

It's true that excess B12 is filtered out by the kidneys and dumped into the urine. However, this takes some time, so that the blood level can remain elevated for a while after taking high-dose methylcobalamin sublingually or by injection. The result is that there is a concentration gradient between the blood plasma and the cells for a while, in the direction that tends to push the methylcobalamin into the cells. It's a transient effect, but by repeating high dosages, over time the levels in the cells will build up. This is what freddd is depending on to get methylcobalamin and adenosylcobalamin into his cells, because the normal processing system apparently does not work in his case.

Please understand that in cases in which high-dose methylcobalamin is helping people, I'm glad. I just know that we all have a tendency to reason that if a little is good, more is better. That is often not true in biochemistry, where the metabolites each have a range of normal values, and either too little or too much can cause problems. So I advocate measuring to see how things are going.

I think we also all have a tendency to reason that if something works well for one person, it will also work in the same way for others. Often this logic works for us, but it's also true that it may not, because we all have a different set of genomic polymorphisms, and people with the symptoms of CFS are a very heterogeneous group, having different things going on.

I spend a considerable amount of time consulting on individual cases, and each one takes a lot of study, because they are all different. I try to find common features that could be dealt with by a "mass production" approach, and the combination of methylation cycle block and glutathione depletion appears to be one of them that is common to many PWCs. But it isn't the whole story. Lifting this block helps most people, but there are other aspects that must be dealt with in individual cases.

And there are reasons why it doesn't work well in some people. So far, I think they include lack of enough of some of the cofactors (especially B-vitamins and some of the essential minerals), lack of enough amino acids (which is probably due to a combination of problems in digestion and absorption as well as the fact that PWCs burn amino acids for energy moreso than normals, because the early part of the Krebs cycle is partially blocked due to glutathione depletion. Carbs and fats have to come in before this partial block, while amino acids can come in after the block).

There are also people who have infectious diseases such as Lyme or its coinfections, or mold illness, and these must be treated in addition. I think we have yet to learn whether viruses, including XMRV, need to be treated also. So it's complicated, and as much as I would like one size to fit all, it doesn't seem to.

Best regards,

Rich
 

dmholmes

Senior Member
Messages
350
Location
Houston
I think that the dosages that will not overdrive the methylation cycle probably vary from one person to another, because we have different sets of polymorphisms in the genes that code for enzymes in the methylation cycle and the related pathways. That's why I recommend periodic testing.

Rich, what are we looking for in the test that points to overdriving methylation?

I was about to do my next methylation panel, disappointing to hear it's going to take that long to get it done. Is the plasma amino acid going be informative for me since I haven't had one before?
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi, all.

I just want to note that methyl B12 has only one known function in the human body, which is to serve as a coenzyme for methionine synthase in the methylation cycle. Adenosyl B12 also has only one known function, and it is to serve as a coenzyme for methylmalonyl-CoA mutase. All the effects of vitamin B12 have been found to derive from these two functions.

Normally, the various forms of B12 in the diet or in supplements at RDA-level dosages go through the normal absorption, transport and intracellular processing and are converted to the amounts of these two coenzymes that are needed by the cells.

When very large dosages of methyl B12 compared to RDA levels are taken sublingually or by injection, the normal absorption, transport and processing of vitamin B12 into these two coenzymes are bypassed. Under these conditions, I think it may be possible to get too much methyl B12 into the cells, and that this could overdrive methionine synthase, so that cystathionine beta synthase will not receive sufficient homocysteine to feed the transsulfuration pathway sufficiently for the production of cysteine, glutathione, taurine, sulfate and other sulfur-containing metabolites. In addition, the methylation capacity might rise too high, which could affect DNA methylation and therefore gene expression. I think this is relatively uncharted territory, and going there may produce some deleterious effects.

Therefore, I think it would be wise to do some testing periodically while on high-dose B12 supplementation. The best test panel is the Vitamin Diagnostics methylation pathways panel. Unfortunately, because of a lab move, the availability of this test will probably be hampered until about the end of January. I think the next best would be a plasma amino acids panel, such as is offered by Doctor's Data Lab. The condition of the methylation cycle and the transsulfuration pathway can be inferred from this panel, though the interpretation is not as direct as with the Vitamin Diagnostics panel.

I again want to note that I think that the response to high-dose B12 treatment will differ for those who have inborn errors of metabolism involving the intracellular B12 processing enzymes and those who do not. It is not normal for a person's body not to be able to use hydroxocobalamin, and it is also not normal for glutathione to interfere with the utilization of B12. In fact, its normal role is to protect B12. The presence of these abnormalities suggests that there is an inborn error of metabolism involving the B12 processing enzymes.

In the past, I have noted that the simplified treatment approach, which utilizes hydroxocobalamin, has been found to help at least two-thirds of the people with CFS who have tried it. It is not clear that the treatment failure in the other nearly one-third is due to their inability to utilize hydroxocobalamin, as freddd has suggested. Rather, it looks as though deficiencies in cofactors or in amino acids are responsible in many cases, based on lab test results I've studied so far.

Best regards,

Rich


Hi Rich,

I just want to note that methyl B12 has only one known function in the human body, which is to serve as a coenzyme for methionine synthase in the methylation cycle

You use your words most carefully and I appreciate that. However, I think many may infer far more meaning from your careful choice of words than you would be willing to state. For instance, the "one known function" certainly appears to be a main function, critical to the maintenance and healing of every tissue in the body. The "upregulation of neural tissue healing" in the central nervous system noted by the Japanese in high dose research appears to be another function. It promotes the healing of myelin lesions among otyher things. The functioning of damaged neural tissue is enhanced when mb12 enters the CSF in sufficient quantity, which ability appears impaired in CFS/FMS/ME patients. The improvment in functioning remains as long as the mb12 level remains relatively high. For instance it is some combination of the effects of mb12 on the central nervous sytem that keeps me at 30mg/day injected. Otherwise a single 5mg sublingual is probably fully sufficient. At 5mg sublingual daily my central neurology deteriorates and I would be in a wheelchair without feeling or control over my lower legs, feet and toes and continual muscle contractures requiring Dilantin and Valium to control.

So MAYBE that is all a result of the single function you mention being performed more completely or maybe it isn't.

Adenosyl B12 also has only one known function, and it is to serve as a coenzyme for methylmalonyl-CoA mutase

Large dose Adb12 also gets into the CSF and does its single function in the neurons. As regards Adb12 I agree fully that it has a single function and it does it quite well. It's amazing the changes that occur when the neuronal mitochondria start working well with adb12 within the CNS. And while I know of no research to document it, there are plenty of persons who can demonstrate it. The effect is quite real. There are 4 clearcut response patterns; body mb12, body adb12, CNS mb12 and CNS adb12.

and it is also not normal for glutathione to interfere with the utilization of B12. In fact, its normal role is to protect B12.

I don't think that there is enough evidence to say that. A significant percentage of people who are paying attention and trying these things find that gutathione does in fact interfer with methylfolate, methylb12 and adenosylb12, but perhaps the interference with the active b12s is secondary to the active folate interference. Even if it is "ONLY" 1/3 of folks for which that happens that is still a very sizable minority.

its normal role is to protect B12.

In sufficient quantity methylb12 doesn't need protection. In fact it's normal role appears to be to detoxify these things that would destroy it and cause the excretion of these toxins. Mb12 needs protection only when it is present in insufficient quantities. In a sense then, protecting b12 is a vital nutrient starvation response to remove it from one of its normal roles when not enough is present and would only be seen in deficiency states. Mb12 removes cyanide from the body, it is disabled by mercury which in turn is excreted by the liver at about 1% per day after reacting witn mb12, it protects against botulism neurotoxin, it protects against tetanus neurotoxin, it protects neurons from glutamate toxicity, it protects neurons from cascading neuronal death, it detoxifes nitrous oxide and removes it from the body. It does these anti toxin things only when presnt in high enough quantioty to do it. In various studies the list of toxins against which it is protective or that it removes is growing regularly now that more research is being done on active b12s instead of the laboratory mistake, cyanocobalamin.

Research over and over notes that mb12 has unique properties not matched by any inactive b12 forms. Mb12 has a dose proportionate healing curve unlioke inactive cobalamins. I and a number of others have explored the characteristics of that curve and found it's characterisitcs at sublingual dose levels and with injections. My internist is simply amazed at what has occurred. I walked into his office 6.5 years ago, slowly dying, typically sick almost all the time with one thing after another each lasting way too long. Now I haven't been sick in 6.5 years. I have gone from 200 sick days a year to ZERO. That in itself is an interesting demonstration. I have gone from total disability to looking for a suitable job or consulting contracts.


When very large dosages of methyl B12 compared to RDA levels are taken sublingually or by injection, the normal absorption, transport and processing of vitamin B12 into these two coenzymes are bypassed. Under these conditions, I think it may be possible to get too much methyl B12 into the cells, and that this could overdrive methionine synthase

Or maybe not. Honestly I don't know either. I would be pleased to provide a blood sample for analytical work and I know many others that would be too. My opinion is that there is a "channel" capacity that can be fully filled but that it isn't overdriven. If it were being overdriven what would be the characteristics? How would this be expressed in symptoms? Diseases? Biochemistry? In the studies done with uremics and very large injections of mb12 they were looking for all sorts of toxic effects and were unable to find any effect at all. The uremics were chosen because they are the only folks who can accumualte tremdously huge serum levels. The rest of us excrete it via the urine at better than 99% per day. It is the proverbial most expensive urine. The most painful side effect of that is paying for it out of pocket. The ONLY reason I am willing to do so is to keep me out of a wheelchair and keep my brain working well. About 3 months of sublinguals only at normal doses and I would not be able to walk.


It is not normal for a person's body not to be able to use hydroxocobalamin, and it is also not normal for glutathione to interfere with the utilization of B12. In fact, its normal role is to protect B12. The presence of these abnormalities suggests that there is an inborn error of metabolism involving the B12 processing enzymes.

It is not clear that the treatment failure in the other nearly one-third is due to their inability to utilize hydroxocobalamin,

There is that word again "NORMAL". It implies to most people far more than a technically correct usage of the term means. Why should anybody be expected to be able to utilize an inactive form of the vitamin, a pseudo vitamin as it were, other than how it is naturally supplied in our foods? Converting it to active is nothing our bodies evolved for. It puts a bias into the biochemistry having to perform this unnatural conversion. This bias is so widepsread that it has become "normal" by the BIG LIE method of frequent repetition.

That "1/3" who fail to utilize hydoxcobalamin is an interesting number. It is solidly in the range established by hundreds of research studies of the percentage of people who have no response to hydroxycobalamin in the area being researched. The range there is 20% to 40% for most studies and as high as 60% in some special situations dealing with inborn processing errors.

So 2/3 have some response to hydroxycobalamin. Statistically that puts it into the plus-minus 1 standard deviation on a normal distribution curve. However, the response is incomplete. It only affects about 1/3 of the symptoms and signs that a combination of mb12 and adb12 do. This can be easily demonstrated.

In a single challange sublingual dose trial, with 5 star rated sublinguals only, I performed over several years with about 1000 people in all, about half of them symptomatic and about half of them without any symptoms that one might expect to be affected. I'm sorry to say I did this on the run without keeping good records and it needs to be repeated with good record keeping. About 95% of those with symptoms had a response within one hour to either mb12, adb12 or both. In the next trial I will obviously have to include hydroxycobalamin and cyanocobalamin in a double blind situation. However, nobody actually expects "just a vitamin" to do anything they would actually notice. Those without symptoms, in good health and all, had a basically zero rate of response. The only ones of those that started up in the symtom free group and had a response were those who after a response said, "Oh. I had forgotten about those symptoms they started so long ago and the doctors never thought they were important" or something similar. They turned out to be symptomatic after all and had a response. It turns out that many of the nonspecific symtoms that doctors routinely ignore and train patients to routinely ignore are in fact low level b12 deficiency symptoms.

The creeping MCV (and corresponding MCH) values in the USA also indicate that a change is happening. Normal values used to be <92-93 depending upon the lab. My internist was shocked to see that I had suddenly healed by doing nothing at all when my alertable 99.8 MCV when the lab was alerting >96 had become non allertable when they changed to >100. It seems that MCV=99.8 has become "normal" since it is now within 2 standard deviations of mean which they explained to me. It seems that so many people were now allertable that the docs were ignoring it. How to LIE with statistics. Normal has a techincal meaning but that is not how most people understand it.

With more people than ever taking vitamins containing inactive b12 and inactive folate and inactive b6, more and more people are becoming borderline macrocytotic.

It is not clear that the treatment failure in the other nearly one-third is due to their inability to utilize hydroxocobalamin, as freddd has suggested. Rather, it looks as though deficiencies in cofactors or in amino acids are responsible in many cases, based on lab test results I've studied so far.

With the active b12s it is very clear when a failure to respond is due to lack of cofators. It appears something like this.

About 5% have total failure to respond due to lack of one or more cofactors, most frequently methylfolate, but including SAM-e, l-carnitine fumarate, magnesium, Zinc and Vitamin D3. Much more common is a limited response.

About 90% have a limited response to some degree or another due to lack of cofactors. Again, the most common needed cofactor is that usually supplied by another pseudo vitamin, folic acid. There is a pattern here. It is the pattern of the "depleted methylator" or "methylation block" being an artifact of inactive pseudo vitamins and lack of the real vitamins. I had it. Lots of people have/had it. Dr Myhill states that the way to unblock it is with Methylb12. What percentage of people develope "methylation block" if they are taking methylb12 and methylfolate all along? Do any develop it under those conditions?



These estimates are based on real world responses, not hypotheses based on lab reports. Lab reports are incredibly non predictive about who will respond to mb12, adb12 or methylfolate. If my treatment were based on lab reports I would be dead or most certainly in a wheelchair by now. The statistics based treatment with these items is ruining health, destroying lives and killing some people.

"NORMAL" is enshrined with values based on chronic deficiency states and poor to borderline funtioning based on 60 years of research and statistics based on inactive pseudo vitamins.

Just this year the new explosion of Ricketts exposed that very problem of low vitamin D. And they were not off by just a little, like a factor of 2. Rather many are suggesting a change of an entire order of magnitude, to 2000-4000 units from 200-400 units.

Again, I think you place far to much importance on my IMEs, whether they are as rare as thought or not. I almost certainly never would have had my CFS crash without being a vegetarian and trusting cyanob12 as a supplement, because I had no choice.
 
Messages
84
web page

fredd , i think u should have a web page where u can explain the whole protocol and answer the critics .. otherwise it seems like u ll have to defend the active b12 theory against the same argument over and over and over ..
i just cant understand why this happens , there comes an argument u answer it and no response to it and then some time later the same argument comes again and u have to anwser it again .. if u had a web page maybe u could just copy paste links here .. in addition the whole protocol could be studied much easier there ..
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Hi Rich--

I want to let you know how much I appreciate your input on this thread. :):):)

I am one of those who has had a very hard time tolerating the active B12's, due to my heavy metal toxicity load. I absolutely CANNOT TAKE HIGH DOSES of the methyl or ad B12 without experiencing major detox reactions. In fact, even small doses (1/2 tab every other day) of either of these can cause overwhelming discomfort for me. So for now, I have given up on them.

I haven't tried the simplified protocol yet, but I am really glad to know it's an option when I'm ready to do so.

Thanks again, Dreambirdie
 

jenbooks

Guest
Messages
1,270
Rich, just updated myself on this thread and saw your cogent, nicely nuanced posts. I appreciate them. It's a delicate balance--and we are best erring on the side of caution.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
fredd , i think u should have a web page where u can explain the whole protocol and answer the critics .. otherwise it seems like u ll have to defend the active b12 theory against the same argument over and over and over ..
i just cant understand why this happens , there comes an argument u answer it and no response to it and then some time later the same argument comes again and u have to anwser it again .. if u had a web page maybe u could just copy paste links here .. in addition the whole protocol could be studied much easier there ..


Hi Lebowski,

You know, it probably will have a web page when I consider this finalized. At this time it is still underconstructiob and debugging. However, I also think that this discussion is important to it's refinement. I look to learn everything I can. The back and forth with Rich is important because he is knowledgeable and brings up important things. He knows a whole lot more about the biochemistry and such than I do. True, I'm challanging some of his ideas and trying to challange some of his assumptions or the basis on which the stand. I like things that I do to be bulletproof. As long as real questions can come up, they need to. One must be careful to distinguish questions that are intellectual devices to gain points as it were to questions about something that make a meaningful and REAL difference. If there are certain situations in which something is dangerous, I think it important to know that. I think it important to know what unintended side effects and consequences are possible and how probable they may be. However, I am quite aware that "statistically significant resuts on a statistically significant number of people" my also amount to nothing at all in the real world. With hydroxyb12 for instance, while it helps some percentage of people with some percentage of symptoms it never produces a level of active b12 in a person that restores them to a level of nonresponsiveness to active b12s across all symptoms such as normal healthy people have. People without b12 deficiency symptoms have no responsivenss to active b12s. Hydroxycobalamin doesn't produce that state no matter how many years taken. Selected b12 deficiency symptoms continue to worsen in many people despite taking hydroxycobalamin often leading to the most intense reactions to mb12 and adb12 being those who have been taking an inactive b12 all along. It is because of the lack of equivalence of results with hydroxycobalmin over any time period that I have difficult accepting the idea that it is an acceptable substitute. Maybe that can be answered. I would certainly like to know if it can be. For that exposure is necessary. I am certainly challanging Rich's ideas and underlying assumptions. And he is challanging mine, which is as it should be. That we agree on almost everything but this one item and a few side issues having come at things from very different directions is what I find amazing and actually rather reassurring of being on the right track.

As I am working from pragmatic response of myself consolodated with hundreds of others most likely without most of my IMEs except for inability to convert folic acid adequately whch afflicts at least 50% of the population, their reasons for being deficient are many varied including the vegetarian which I have run affoul of too. Not one of them has found hydroxyb12 to be a satisfactory complete substitute for either of the real active b12s. When I have a theory presented that disagrees with real world results, I go with the real world results. So theory has to change to account for real world results.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi Rich,

As far as I can tell your objections all boil down to dose quantity and the possible uninteded side effects. As there is a very substantial qualitative difference I think that even very small doses will have superior results. So is there any reason you would object to 30mcg a day of each kind of active b12, or if not that, then name a number that meets with your satisfaction. That is easy enough to approximately do in any of several ways.

Now these small doses will in no way affect the supressed CSF/CNS cobalamin that has been identified in FMS/CFS which cause a huge amount of the central symptoms. They will certainly be a superior start to hydroxycobalamin. They will not have the same effectiveness as the higher dosage of unbound b12s. It will be interesting to see the effects. At least they will remove 100% of the uncertainty around all the gymnastics the body has to do to use hydroxyb12. So there is the challange for whomever wishes to try a low dose approach. Use the low dose of combined active cobalamins and lets see the differences from hydroxyb12 on the same amount of active b12s that in theory, the hydroxyb12 is converted to. Let's see if the results are about the same as theory says they should be.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi Rich--

I want to let you know how much I appreciate your input on this thread. :):):)

I am one of those who has had a very hard time tolerating the active B12's, due to my heavy metal toxicity load. I absolutely CANNOT TAKE HIGH DOSES of the methyl or ad B12 without experiencing major detox reactions. In fact, even small doses (1/2 tab every other day) of either of these can cause overwhelming discomfort for me. So for now, I have given up on them.

I haven't tried the simplified protocol yet, but I am really glad to know it's an option when I'm ready to do so.

Thanks again, Dreambirdie


Hi Dreambirdie,

How about taking the challange of tiny doses of active b12s at the level at which the hydroxyb12 is theoretically supposed to convert at. Try it and see if they really are the same or if hydroxyb12 doesn't really convert. I posted a micro dose method recently. Other methods can be used such as crumbs etc.
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Hi Dreambirdie,

How about taking the challange of tiny doses of active b12s at the level at which the hydroxyb12 is theoretically supposed to convert at. Try it and see if they really are the same or if hydroxyb12 doesn't really convert. I posted a micro dose method recently. Other methods can be used such as crumbs etc.

Hi Freddd--

Maybe in the future. Definitely not right now. What page is that micro dose method on?
 
Messages
84
hi fredd ,

people on the protocol come here to tell their experiences , side effects , good effects , their feelings about what they live .. and of course for ur invaluable guidance for a problem which is still unsolved in scientific history..it is invaluable cause no one knows ur protocol as u do and it is just the same for the simplified meth. block theory for rich .. i appreciate all these information very much ( i exclude the objections to the protocol here like
" my mother who is 97 with terminal cancer tried the protocol , she had a rash and my poor old mother was very afraid when she saw the rash , now i think no one who is not a doctor should give medical advise online , where is our government ! .. " ) ( and it is not medical advice but medical option one can choose to go into or not i know fredd ..but she doesn't know : )

my point on previous post was different tough .. there should be a scientific challenge for sure which is the healthy way .. but come on it should not be the same scientific challenge every time .. the scientific argument stops when u answer an objection and it doesn't start from the place it was left at a later time , it just starts from the beginning .. looks like the movie bill murray lived the same day over and over again (i forgot the name of the movie sure ) .. it is just like u never made an explanation for the same argument .. i still think a developing web page can be made for the protocol in which u could answer the questions , objections , etc and update them as u like .. but sure u know best how u should use ur resources .. again thanks to u to rich and to everyone writing with a real reason ..
 

DrD

Messages
45
Hi, Marylib and Dr D.

I've expressed two concerns on this board in the past: possible methylation of inorganic mercury and movement of it into the brain, and the high dosages relative to what PWCs can tolerate in the presence of detox.

Another concern, which I've expressed on other boards in the past but perhaps not here, is that I believe that the goal should be to restore the methylation cycle to normal operation, not to overdrive it. This issue has come up several times in connection with concerns about cancer. It is known that methylation is abnormal in cancer cells. The tumor suppressor genes are overmethylated, silencing them, and the oncogenes are undermethylated. I don't think it's understood how this occurs.

There is a mechanism built into cells to limit the ratio of SAMe to SAH in the methylation cycle, involving glycine and sarcosine. I think there must be a reason for the presence of this mechanism, and it is probably intended to prevent overmethylation. My concern is that I suspect that it is possible to override this putative safety mechanism if large enough dosages of methylcobalamin are used.

I think that in order to make sure that the methylation cycle is not being overdriven, it is prudent to run a test periodically to see how it's doing, especially if very high dosages of methyl B12 are being used. I have recommended the same for the Simplified Treatment Approach, which uses a fairly high dosage of hydroxo B12, on other boards.

I just think people should be cautious about this, since I don't think possible effects of overdriving the methylation cycle are well understood.

Rich

hi Rich can you indicate which tests (are they all blood serum tests?) that would be required for measuring the various aspects of the methylation cycle? I can try to educate my doctor and have the tests run, and then post the results for you to analyze.
 

richvank

Senior Member
Messages
2,732
Hi, all.

Lots of good questions and issues have been raised. I'm going to be out today, but I'll try to respond to them tomorrow. Maybe we can get some closure on some of them, and bring the results of the pragmatic approach together with the biochemical picture, to the degree it is known at present. It all has to fit together somehow, because truth is truth. We just have to find it. Thanks for everyone's input.

Best regards,

Rich
 

dmholmes

Senior Member
Messages
350
Location
Houston
Hi, all.

Lots of good questions and issues have been raised. I'm going to be out today, but I'll try to respond to them tomorrow. Maybe we can get some closure on some of them, and bring the results of the pragmatic approach together with the biochemical picture, to the degree it is known at present. It all has to fit together somehow, because truth is truth. We just have to find it. Thanks for everyone's input.

Best regards,

Rich

Rich and Fred, anything we can do to assist with further collaboration between you guys? Maybe take up a donation?