Methylation protocol and glutathione

[Vegas]

Correct me if I am wrong, but doesn't this study just suggest that the caffeine

is doing just what other stimulants do, they increase dopamine and stimulate methylation on a temporary basis. Does this really result in any net gains, and does this apply to a human with low glutathione. Obviously improvement in lipid peroxidation, SOD activity etc., is desirable; however, I wonder how well this translates to someone who has abnormal methylation capacity. In someone with low glutathione would this have any lasting consequence if they are not correcting the limiting factors. I would have to speculate that there is a consequence to this binge since glutathione resources are finite, and a temporary rise in brain concentration could result in deficits later. At least that is how I have always looked at it; everyone has finite resources, but ours are much more susceptible to the effects of stimulating energy.

In this study, caffeine seems to increase reduced glutathione in the rat brain:

Pharmacol Biochem Behav. 2011 Jun 15. [Epub ahead of print]
Chronic coffee and caffeine ingestion effects on the cognitive
function and antioxidant system of rat brains.
Abreu RV, Silva-Oliveira EM, Moraes MF, Pereira GS, Moraes-Santos T.
Laboratrio de Nutrio Experimental (LNE), Faculdade de Farmcia,
Universidade Federal de Minas Gerais, Av. Antnio Carlos, 6627,
Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil; Ncleo de
Neurocincias, Departamento de Fisiologia e Biofsica, Instituto de
Cincias Biolgicas, Universidade Federal de Minas Gerais, Av. Antnio
Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901,
Brazil, 31270-901.
Coffee is a popular beverage consumed worldwide and its effect on
health protection has been well studied throughout literature. This
study investigates the effect of chronic coffee and caffeine ingestion
on cognitive behavior and the antioxidant system of rat brains. The
paradigms of open field and object recognition were used to assess
locomotor and exploratory activities, as well as learning and memory.
The antioxidant system was evaluated by determining the activities of
glutathione reductase (GR), glutathione peroxidase (GPx) and
superoxide dismutase (SOD), as well as the lipid peroxidation and
reduced glutathione content. Five groups of male rats were fed for
approximately 80days with different diets: control diet (CD), fed a
control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both
fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and
0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented
with caffeine. The estimated caffeine intake was approximately 20 and
40mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments,
respectively. At 90days of life, the animals were subjected to the
behavioral tasks and then sacrificed. The results indicated that the
intake of coffee, similar to caffeine, improved long-term memory when
tested with object recognition; however, this was not accompanied by
an increase in locomotor and exploratory activities. In addition,
chronic coffee and caffeine ingestion reduced the lipid peroxidation
of brain membranes and increased the concentration of reduced-
glutathione. The activities of the GR and SOD were similarly
increased, but no change in GPx activity could be observed. Thus,
besides improving cognitive function, our data show that chronic
coffee consumption modulates the endogenous antioxidant system in the
brain. Therefore, chronic coffee ingestion, through the protection of
the antioxidant system, may play an important role in preventing age-
associated decline in the cognitive function.
Copyright 2011. Published by Elsevier Inc.
PMID: 21693129 [PubMed - as supplied by publisher]

 

[Waverunner]

is doing just what other stimulants do, they increase dopamine and stimulate methylation on a temporary basis. Does this really result in any net gains. In someone with low glutathione would this have any lasting consequence if they are not correcting the limiting factors. I would have to speculate that there is a consequence to this binge since glutathione resources are finite, and a temporary rise in brain concentration could result in deficits later.

Well, that's an interesting question. In my eyes 90 days are pretty long for a short term effect but this cannot be excluded of course. Moreover I don't know how long after the last caffeine intake, they measured glutathione. And last but not least we have to ask ourselves if human brains react accordingly.

 

[Dreambirdie]

When sufficiently large amounts of both methylfolate and methylcobalamin are supplied to a cell, these feedback loops are overridden. The result is that the activity of methionine synthase remains high, regardless of the body's needs. The effect of this is to cause both the methylation cycle and the folate cycle to run faster than normal, while the flow down the transsulfuration pathway to make cysteine (needed for the sythesis of glutathione) and also to make coenzyme A, taurine, sulfate and other sulfur-containing metabolites that are needed for a variety of purposes, is held lower than normal.

I don't know what the long-term consequences of this will be. What I see in the test results of people who are supplementing both methylfolate and methylcobalamin at dosages in the several milligrams per day range are indications that glutathione is not coming up, while the methylation cycle and folate metabolism are carrying out a "futile cycle" by passing methyl groups back and forth between them via sarcosine and methylfolate. As a minimum, it seems to me that this would slow their recovery.

Thanks for this explanation, Rich. The methylB12 has been an ongoing problem for me, even with using the TD-glutathione to assist the flood of toxicity that results when I take more than a smidge. I wish I had the funds to do a lab test to see if it actually causes over-methylation, but since I don't, I am going to opt for the hydroxo for my next round of this protocol.

There is nothing sacred about the simplified protocol as far as I'm concerned. If an individual finds something that works better for them, my attitude is more power to them! I'm a researcher, not a clinician, and I see my role as trying to figure out what's going on in this disorder. Hopefully that will provide clues to treatment, but it isn't straightforward to determine the best treatment protocol simply on the basis of biochemical theory.

For one thing, people are all unique in terms of their genetics, and I have to object when treatment results for an individual or a group of individuals are extrapolated and claimed to apply to all cases. They may indeed apply to many others, but I have seen enough heterogeneity in the ME/CFS population that I don't believe in one-size-fits-all treatments, and sometimes there can be unpleasant surprises when this approach is taken.

This is what I appreciate most about your approach. Being open to what works for each individual is the best way to go.

 

[mellster]

Well, that's an interesting question. In my eyes 90 days are pretty long for a short term effect but this cannot be excluded of course. Moreover I don't know how long after the last caffeine intake, they measured glutathione. And last but not least we have to ask ourselves if human brains react accordingly.

I think this depends on the individual and if it is otherwise well tolerated - if my stomach permits I do drink coffee/espresso in moderation (recommend it on a full stomach) and energy-wise it makes me feel better without crashing later. It could be very well some of the additional supplements for some people in a modified methylation protocol.

 

[Richard Lee]

Hi, Richard.

I don't know enough to give simple answers to your questions (above). I think that all three of the aspects you mentioned are potential issues.

At this point, the only way I can tell whether the amounts an individual is taking are causing the overdriving problem I'm concerned about is to see certain types of lab test results on that person.

My goal in commenting on treatment of the vicious circle mechanism that I believe is associated with the partial methylation cycle block in ME/CFS is to try to help people with ME/CFS to restore this part of the metabolism to normal operation, because I believe it's the core issue in this disorder.

What I can do is to describe the situation in the biochemistry as I see it, based on what is known about this part of the metabolism as applied to the interpretation of test results that some people have sent me.

In normal operation, the activity of the methionine synthase enzyme (which I believe, based on lab testing, is partially blocked in ME/CFS) is continuously varied to balance the body's needs for methyl groups, folate vitamers, and antioxidant protection. There are several feedback loops involved in this overall system that normally balance the response to these needs.

When sufficiently large amounts of both methylfolate and methylcobalamin are supplied to a cell, these feedback loops are overridden. The result is that the activity of methionine synthase remains high, regardless of the body's needs. The effect of this is to cause both the methylation cycle and the folate cycle to run faster than normal, while the flow down the transsulfuration pathway to make cysteine (needed for the sythesis of glutathione) and also to make coenzyme A, taurine, sulfate and other sulfur-containing metabolites that are needed for a variety of purposes, is held lower than normal.

I don't know what the long-term consequences of this will be. What I see in the test results of people who are supplementing both methylfolate and methylcobalamin at dosages in the several milligrams per day range are indications that glutathione is not coming up, while the methylation cycle and folate metabolism are carrying out a "futile cycle" by passing methyl groups back and forth between them via sarcosine and methylfolate. As a minimum, it seems to me that this would slow their recovery.

If a person should also happen to have inherited a slow version of the enzyme glycine N-methyltransferase, which some people have, this overdriving of the methylation cycle could cause the SAMe level to rise high above normal, and that would affect gene expression as well as the rates of a large number of methyltransferase reactions. I can't predict the outcome of that.

Methylation is also involved in cancer, in silencing tumor suppressor genes, so elevating the availability of methyl groups above normal levels, such as might occur if the glycine N-methyl transferase activity is low for genetic reasons, could potentially have some effect on that as well.

It's known that cancer cells have a higher demand for B12 and folate and have higher numbers of receptors for them than normal cells do, presumably to support their more rapid multiplication, so that if there are incipient cancers present, high dosing of these two together could potentially accelerate tumor growth. One person reported activation of a long-dormant incipient skin cancer (actinic keratosis) on this type of treatment.

In theory, methylcobalamin can methylate inorganic mercury, making it fat-soluble and able to cross the blood-brain barrier. When sublingual methylcobalamin is held in contact with teeth that have amalgam fillings for long times, it would seem that the concentrations of both methylcobalamin and inorganic mercury could be high enough to achieve a significant reaction rate and significant production of methylmercury.

All this having been said, some PWCs do need to take the methyl form of B12 because of their particular inherited genetic polymorphisms. Dr. Amy Yasko bases the choice of which form to use on characterization of these polymorphisms. In suggesting the simplified approach, I decided to opt for hydroxocobalamin in the basic protocol, and it was found to work for most of the PWCs in our clinical trial. The idea was to enable people to do something that has a good chance of helping, without the cost and complexity of the full Yasko program. I did this with the knowledge that this protocol would not be optimum for everyone, but it is a place to start. When people observe effects from the simplified protocol, they become interested in the methylation issue, and then they are motivated to look into it further, perhaps get some testing if it is feasible for them to do so, and perhaps modify their treatment to something that is a better match for them.

If a PWC finds that the simplified protocol does not work for them after two or three months, I suggest doing some testing to find out why, and changing the treatment appropriately. I favor using the smallest dosage that will do the job, so that the body will be able to balance its needs by regulating this part of the metabolism as well as it can.

I also recommend working with a physician while on this type of treatment. If injections are feasible in a person's situation, that is certainly an option. As Freddd has pointed out, it's important that the injected solution be of good quality and properly prepared, as methylcobalamin does not have high chemical stability.

There is nothing sacred about the simplified protocol as far as I'm concerned. If an individual finds something that works better for them, my attitude is more power to them! I'm a researcher, not a clinician, and I see my role as trying to figure out what's going on in this disorder. Hopefully that will provide clues to treatment, but it isn't straightforward to determine the best treatment protocol simply on the basis of biochemical theory.

For one thing, people are all unique in terms of their genetics, and I have to object when treatment results for an individual or a group of individuals are extrapolated and claimed to apply to all cases. They may indeed apply to many others, but I have seen enough heterogeneity in the ME/CFS population that I don't believe in one-size-fits-all treatments, and sometimes there can be unpleasant surprises when this approach is taken.

I also believe that when judging the effects of a treatment, we need to define the treated population as tightly as we can. If we are looking at an undefined population that includes people with the whole variety of B12-related problems, and not only those who satisfy the (admittedly imprecise) criteria for ME/CFS, I think we have to question how applicable the results are to the ME/CFS population.

I again want to reiterate that I very much appreciate the contribution that Freddd has made to this field. I think we can learn a lot from his experience, and I certainly have myself. My concern is that we examine it in the light of Freddd's own situation, which he has shared with us, and apply it appropriately to other cases. There is still a great deal that we don't know about ME/CFS, the metabolism related to the methylation cycle, and how to apply appropriate treatment. I also very much appreciate reading reports of the experiences of people in these forums. These experiences are a big part of the "acid test" for me of whether my hypotheses make sense or not.

Best regards,

Rich

Thank you, Rich, for patiently explaining the ideas behind your protocol. It's given me much food for thought.

I'm not sure how many people would be taking "both methylfolate and methylcobalamin at dosages in the several milligrams per day range". I myself am taking 800mcg methylfolate and 10mg sublingual (i.e. perhaps 1.5mg absorbed) methylcobalamin, and I would be curious to know if my testing reveals "futile cycles". Which test is it that would define this?

I know that Freddd himself is taking doses in the higher range, but he has also titrated it to find the minimum that works for him, and therefore satisfies your "smallest dosage that will do the job". I would be very curious to see Freddd's test results.

It is true that cancer cells have a voracious appetite for B12. But surely they will get a disproportionate share of B12 even if they are fed conventionally by holoTC instead of by diffusion, due to their higher number of TC-receptors. Perhaps diffusion might even distribute B12 more equitably.

Also the chain of causation might be the other way around: someone's B12 might have become low BECAUSE his cancer-cells were stealing the lion's share, or because his body ran low levels of B12 deliberately to frustrate the cancer cells.
William S Beck 1995: "In cancer patients, values of holoTC and RBC-Cbl were subnormal."

The risk of methyl-mercury is of concern to me. I wish that there were some conclusive research. I would like to experiment with hydroxocbl as an alternative, but I am not sure that I can switch with impunity. Once started on these B12 protocols, it often seems to be a case of "crash through or crash".

The other concern that I have about B12 therapy, which applies equally to hydroxo- as well as to methyl-cobalamin, is the possibility of an immune-reaction to B12 itself. If high supplementation is likely to saturate the body's TC and HC, there is a risk to someone (like me) who is prone to allergies that he will eventually develop an IgG-IgM-B12 immune-complex. I refer to two recent papers:
2006 Markedly Increased Vitamin B12 Concentrations Attributable to IgG-IgMVitamin B12 Immune Complexes
2010 An IgG-complexed form of vitamin B12 is a common cause of elevated serum concentrations

The immune-complex shows up on conventional B12 tests as an elevated (and misleading) level for serum B12. The long-term implications are unknown. Even the saturation of haptocorrin is problematic, because the consequent proliferation of inactive B12 analogs might interfere with B12 metabolism and cause "setbacks".

Altogether there is a daunting number of unknowns with B12 therapy. Yet inaction is not an option. I'd rather take my chances with a shark-infested ocean than remain on a burning boat. I appreciate that you and Freddd are helping us navigate treacherous waters.

 

[richvank]

***Hi, Richard.

Thank you, Rich, for patiently explaining the ideas behind your protocol. It's given me much food for thought.

***You're very welcome. I've been appreciating your contributions to these forums also.

I'm not sure how many people would be taking "both methylfolate and methylcobalamin at dosages in the several milligrams per day range". I myself am taking 800mcg methylfolate and 10mg sublingual (i.e. perhaps 1.5mg absorbed) methylcobalamin, and I would be curious to know if my testing reveals "futile cycles". Which test is it that would define this?

***I don't know how many are doing it, either, though I think quite a few have been following Freddd's protocol, which features dosages in this range. I would be interested to know how your test data would look, too. From what you've posted, it sounds as though you might have developed an absolute B12 deficiency, rather than only a functional deficiency, which appears to be involved in most cases of ME/CFS.

***The tests I have been using to characterize this situation are a combination of the methylation pathways panel (offered by the European Laboratory of Nutrients in the Netherlands and the Health Diagnostics and Research Institute in New Jersey, USA), the Genova Diagnostics Metabolic Analysis Profile or the Metametrix Organix urine organic acids tests, and the Metametrix plasma 40-amino acids test or the Doctor's Data urine amino acids test. I also like to see results of the Doctor's Data Lab urine toxic and essential elements test. People in Australia have been ordering the first one from the lab in the Netherlands, using FedEx shipping with a regular ice pack. I believe that Metametrix serves Australia. With this combination, it is possible to see what's going on in the methylation cycle, the folate metabolism, and the sulfur metabolism in general, including glutathione.

I know that Freddd himself is taking doses in the higher range, but he has also titrated it to find the minimum that works for him, and therefore satisfies your "smallest dosage that will do the job". I would be very curious to see Freddd's test results.

***I would be very curious to see test results on Freddd, also. However, he has several times expressed his view that testing is not of much value, and prefers to govern his treatment by observing his symptoms. And of course, there is a financial cost involved in getting all these tests run, and I know that that is an important factor for most of us. I think that Freddd has some interesting genomic features that may not be shared by very many in the ME/CFS community, but that has not been pinned down.

It is true that cancer cells have a voracious appetite for B12. But surely they will get a disproportionate share of B12 even if they are fed conventionally by holoTC instead of by diffusion, due to their higher number of TC-receptors.

***I suspect that you are correct about this.

Perhaps diffusion might even distribute B12 more equitably.

***Maybe, but the important thing in cancer promotion may not be how equitable the distribution is, but what the absolute amount is that gets into the cancer cells. The more B12 that is taken, the higher this would be expected to be.

Also the chain of causation might be the other way around: someone's B12 might have become low BECAUSE his cancer-cells were stealing the lion's share, or because his body ran low levels of B12 deliberately to frustrate the cancer cells.
William S Beck 1995: "In cancer patients, values of holoTC and RBC-Cbl were subnormal."

***I expect that the latter is more likely, i.e. that the cancer cells are scooping up the B12.

The risk of methyl-mercury is of concern to me. I wish that there were some conclusive research. I would like to experiment with hydroxocbl as an alternative, but I am not sure that I can switch with impunity. Once started on these B12 protocols, it often seems to be a case of "crash through or crash".

***I, too, wish there was better research on this topic. There is a paper involving guinea pigs that indicates that mercury can be methylated by methyl B12, but it isn't clear whether it happened in bacteria in the gut of the animals, or in their own metabolism. I don't know whether switching to hydroxo B12 would cause you to crash.

The other concern that I have about B12 therapy, which applies equally to hydroxo- as well as to methyl-cobalamin, is the possibility of an immune-reaction to B12 itself. If high supplementation is likely to saturate the body's TC and HC, there is a risk to someone (like me) who is prone to allergies that he will eventually develop an IgG-IgM-B12 immune-complex. I refer to two recent papers:
2006 Markedly Increased Vitamin B12 Concentrations Attributable to IgG-IgMVitamin B12 Immune Complexes
2010 An IgG-complexed form of vitamin B12 is a common cause of elevated serum concentrations

The immune-complex shows up on conventional B12 tests as an elevated (and misleading) level for serum B12. The long-term implications are unknown. Even the saturation of haptocorrin is problematic, because the consequent proliferation of inactive B12 analogs might interfere with B12 metabolism and cause "setbacks".

***I hadn't been aware of the autoimmune problem in connection with B12. Thanks for the information. One thing that might be of interest: I just read in the Science News magazine that vitamin D can help to prevent the immune system from developing autoimmune reactions. There is quite a bit of evidence that many people are too low in vitamin D, especially those who don't get much exposure to sunshine.

Altogether there is a daunting number of unknowns with B12 therapy. Yet inaction is not an option. I'd rather take my chances with a shark-infested ocean than remain on a burning boat. I appreciate that you and Freddd are helping us navigate treacherous waters.

***Yes, I guess we all have to do risk-benefit analyses in the light of our own situations. I hope you will be able to successfully dodge the sharks as well as the fire!

***Best regards,

***Rich

 

[Freddd]

***Hi, Richard.

Originally Posted by Richard Lee Thank you, Rich, for patiently explaining the ideas behind your protocol. It's given me much food for thought.

***You're very welcome. I've been appreciating your contributions to these forums also.

I'm not sure how many people would be taking "both methylfolate and methylcobalamin at dosages in the several milligrams per day range". I myself am taking 800mcg methylfolate and 10mg sublingual (i.e. perhaps 1.5mg absorbed) methylcobalamin, and I would be curious to know if my testing reveals "futile cycles". Which test is it that would define this?

***I don't know how many are doing it, either, though I think quite a few have been following Freddd's protocol, which features dosages in this range. I would be interested to know how your test data would look, too. From what you've posted, it sounds as though you might have developed an absolute B12 deficiency, rather than only a functional deficiency, which appears to be involved in most cases of ME/CFS.

***The tests I have been using to characterize this situation are a combination of the methylation pathways panel (offered by the European Laboratory of Nutrients in the Netherlands and the Health Diagnostics and Research Institute in New Jersey, USA), the Genova Diagnostics Metabolic Analysis Profile or the Metametrix Organix urine organic acids tests, and the Metametrix plasma 40-amino acids test or the Doctor's Data urine amino acids test. I also like to see results of the Doctor's Data Lab urine toxic and essential elements test. People in Australia have been ordering the first one from the lab in the Netherlands, using FedEx shipping with a regular ice pack. I believe that Metametrix serves Australia. With this combination, it is possible to see what's going on in the methylation cycle, the folate metabolism, and the sulfur metabolism in general, including glutathione.

I know that Freddd himself is taking doses in the higher range, but he has also titrated it to find the minimum that works for him, and therefore satisfies your "smallest dosage that will do the job". I would be very curious to see Freddd's test results.

***I would be very curious to see test results on Freddd, also. However, he has several times expressed his view that testing is not of much value, and prefers to govern his treatment by observing his symptoms. And of course, there is a financial cost involved in getting all these tests run, and I know that that is an important factor for most of us. I think that Freddd has some interesting genomic features that may not be shared by very many in the ME/CFS community, but that has not been pinned down.

It is true that cancer cells have a voracious appetite for B12. But surely they will get a disproportionate share of B12 even if they are fed conventionally by holoTC instead of by diffusion, due to their higher number of TC-receptors.

***I suspect that you are correct about this.

Perhaps diffusion might even distribute B12 more equitably.

***Maybe, but the important thing in cancer promotion may not be how equitable the distribution is, but what the absolute amount is that gets into the cancer cells. The more B12 that is taken, the higher this would be expected to be.

Also the chain of causation might be the other way around: someone's B12 might have become low BECAUSE his cancer-cells were stealing the lion's share, or because his body ran low levels of B12 deliberately to frustrate the cancer cells.
William S Beck 1995: "In cancer patients, values of holoTC and RBC-Cbl were subnormal."

***I expect that the latter is more likely, i.e. that the cancer cells are scooping up the B12.

The risk of methyl-mercury is of concern to me. I wish that there were some conclusive research. I would like to experiment with hydroxocbl as an alternative, but I am not sure that I can switch with impunity. Once started on these B12 protocols, it often seems to be a case of "crash through or crash".

***I, too, wish there was better research on this topic. There is a paper involving guinea pigs that indicates that mercury can be methylated by methyl B12, but it isn't clear whether it happened in bacteria in the gut of the animals, or in their own metabolism. I don't know whether switching to hydroxo B12 would cause you to crash.

The other concern that I have about B12 therapy, which applies equally to hydroxo- as well as to methyl-cobalamin, is the possibility of an immune-reaction to B12 itself. If high supplementation is likely to saturate the body's TC and HC, there is a risk to someone (like me) who is prone to allergies that he will eventually develop an IgG-IgM-B12 immune-complex. I refer to two recent papers:
2006 Markedly Increased Vitamin B12 Concentrations Attributable to IgG-IgMVitamin B12 Immune Complexes
2010 An IgG-complexed form of vitamin B12 is a common cause of elevated serum concentrations

The immune-complex shows up on conventional B12 tests as an elevated (and misleading) level for serum B12. The long-term implications are unknown. Even the saturation of haptocorrin is problematic, because the consequent proliferation of inactive B12 analogs might interfere with B12 metabolism and cause "setbacks".

***I hadn't been aware of the autoimmune problem in connection with B12. Thanks for the information. One thing that might be of interest: I just read in the Science News magazine that vitamin D can help to prevent the immune system from developing autoimmune reactions. There is quite a bit of evidence that many people are too low in vitamin D, especially those who don't get much exposure to sunshine.

Altogether there is a daunting number of unknowns with B12 therapy. Yet inaction is not an option. I'd rather take my chances with a shark-infested ocean than remain on a burning boat. I appreciate that you and Freddd are helping us navigate treacherous waters.


***Yes, I guess we all have to do risk-benefit analyses in the light of our own situations. I hope you will be able to successfully dodge the sharks as well as the fire!

***Best regards,

***Rich

Hi Rich and Richard,

A few comments on the things said here. The research that speaks of "B12" without specifying what cobalamin is being considered is speaking of cyanocbl by definition. Methylb12 and adenosylb12 are both "b12 analogs"

Methylb12 is being researched for it's anti-cancer properties. Methylb12 is being researched for it's lack playing a role in the cause of a dozen or so cancers.

B12 deficiency is known to cause at least two autoimmune diseases and is suspected as a cause of others.

I am not against testing. I spent out of pocket (not insured) approximate US$200,000 over 20 years in the dollars of the time for testing and treatment based on that testing. It was 100% a total waste of time and money. Testing and treatment based on studies done on cyanocbl and hydroxycbl don't have relevant interpretations and lead the physicians to wrong and ineffective conclusions.

 

[L'engle]

B12 deficiency is known to cause at least two autoimmune diseases and is suspected as a cause of others.

Hi Freddd,

Which autoimmune diseases are linked with B12 deficiency? Thanks!

 

[Freddd]

Hi Freddd,

Which autoimmune diseases are linked with B12 deficiency? Thanks!

Hi L'engle,

Hashimoto's thyroiditis. If it is still in active phase there is a little evidence that it can reverse with the mb12. The other one is the process that develops antibodies to intrinsic factor. Some others are suspected. Mb12 (and Metafolin) deficiency causes hyper-responsiveness in multiple ways (MCS, allergies, asthma, neurological, smell, taste, sensation, pain, startlement) and causes havoc with the immune system.

 

[richvank]

Hi L'engle,

Hashimoto's thyroiditis. If it is still in active phase there is a little evidence that it can reverse with the mb12. The other one is the process that develops antibodies to intrinsic factor. Some others are suspected. Mb12 (and Metafolin) deficiency causes hyper-responsiveness in multiple ways (MCS, allergies, asthma, neurological, smell, taste, sensation, pain, startlement) and causes havoc with the immune system.

Hi, Freddd and the group.

For what it's worth, my hypothesis for Hashimoto's thyroiditis in ME/CFS is that glutathione becomes depleted in the thyroid gland. Normally, the thyroid makes hydrogen peroxide for use in oxidizing iodide ions in the pathway for making the thyroid hormones. Normally, the thyroid cells themselves are protected from damage due to this self-produced hydrogen peroxide by glutathione. When it becomes depleted, the hydrogen peroxide is able to oxidize proteins in the thyroid, and the immune system views them as foreign substances and mounts an autoimmune attack against them. The basic model for this is due to Duthoit, et al.

Glutathione depletion can result from B12 deficiency because methylcobalamin is needed as a cofactor for methionine synthase. If it becomes depleted, the methylation cycle drains metabolites into the transsulfuration pathway, and the entire sulfur metabolism becomes dysfunctional, including the synthesis of glutathione, and this precipitates Hashimoto's thyroiditis in the thyroid gland.

Best regards,

Rich

 

[Freddd]

Hi, Freddd and the group.

For what it's worth, my hypothesis for Hashimoto's thyroiditis in ME/CFS is that glutathione becomes depleted in the thyroid gland. Normally, the thyroid makes hydrogen peroxide for use in oxidizing iodide ions in the pathway for making the thyroid hormones. Normally, the thyroid cells themselves are protected from damage due to this self-produced hydrogen peroxide by glutathione. When it becomes depleted, the hydrogen peroxide is able to oxidize proteins in the thyroid, and the immune system views them as foreign substances and mounts an autoimmune attack against them. The basic model for this is due to Duthoit, et al.

Glutathione depletion can result from B12 deficiency because methylcobalamin is needed as a cofactor for methionine synthase. If it becomes depleted, the methylation cycle drains metabolites into the transsulfuration pathway, and the entire sulfur metabolism becomes dysfunctional, including the synthesis of glutathione, and this precipitates Hashimoto's thyroiditis in the thyroid gland.

Best regards,

Rich

Hi Rich,

Thank you for the insight into possible mechanisms. A hydrogen peroxide mechanism appears to be at work in the whitening of hair from b12 deficiency as we have previously discussed. Would this basically be the same or similar mechanism with the H2O2? Could there be a similar mechanism at work in other autoimmune responses including parietal cell and IF antibody production? I'm thinking of Lupus too among other things.

 

[redo]

Interesting thread. I have heard of several people whom have had great effects from glutathione (I.V. not oral, because of the hardship of getting high doses orally). Many feel it within the day, if not hour. Anyone who knows someone who's done glutathione IV? I think K. De Meirleir gives suppositories with it.

 

[leela]

Redo,
I have done IV GSH. I get equally good results (if not better, due to being able to administer as needed) from the TD GSH available from Lee Silsby compounding pharmacy. You need someone to Rx it, but the pharmacists are very helpful in assisting the prescribing physician who may not be familiar with it (most aren't.)

 

[redo]

What's TD GSH? Are they tablets or suppositories?

 

[richvank]

What's TD GSH? Are they tablets or suppositories?

Hi, redo.

The "TD" stands for transdermal. It is applied to the skin.

Rich

 

[lucyhem]

how to assess what kind of B12 will be best for me

I don't think that the HydroxyB12 is working for me in the SMP. I might have a slight adverse reaction to it or the fillers. I have had that reaction in the past to sublingual B12 as well. I have also had a months trial on methylB12 injections several years ago for neuropathy from Wellness Pharmacy, before SMP, without much response either way. I do suspect that B12 is important for me as I have many nervous system symptoms and have this feeling at times that my cells are starving that the methylfolate seems to address. How do I assess, make some trials about what kind of B12 to try? I will be getting the Great Plains OAT test. Will that tell me more about B12 use? Does it make sense to do that while I am a month into the SMP protocol? Or should I go off of the protocol for a short time so I have a baseline?

 

[hixxy]

I've tried TD glutathione in the past and found it was hard to get a decent amount into your system this way. Has anyone tried liposomal glutathione as an alternative?

 

[richvank]

I don't think that the HydroxyB12 is working for me in the SMP. I might have a slight adverse reaction to it or the fillers. I have had that reaction in the past to sublingual B12 as well. I have also had a months trial on methylB12 injections several years ago for neuropathy from Wellness Pharmacy, before SMP, without much response either way. I do suspect that B12 is important for me as I have many nervous system symptoms and have this feeling at times that my cells are starving that the methylfolate seems to address. How do I assess, make some trials about what kind of B12 to try? I will be getting the Great Plains OAT test. Will that tell me more about B12 use? Does it make sense to do that while I am a month into the SMP protocol? Or should I go off of the protocol for a short time so I have a baseline?

Hi, Lucy.

It is difficult to sort out whether there is a reaction to the supplements or whether the detox system is mobilizing toxins because it has started to function better as a result of the supplements. I am currently suggesting that people stick with the SMP for three months before deciding whether it's helping or not. If it doesn't seem to be producing positive results by three months, then I think something needs to be changed.

When you had the trial on methyl B12 injections, were you also supplementing active folate, such as methylfolate? If not, this may be the reason you did not experience a response. It's necessary to supplement B12 and folate together to lift the partial methylation cycle block. From what you've reported, it does seem that you receive a positive response to methylfolate.

The easiest thing to do to try to determine which B12 is best for you is to try one for 3 months, and if it isn't helping, try the other.

If you are planning to run a urine organic acids test, I would recommend the Genova Diagnostics Metabolic Analysis Profile, because it has both Figlu and MMA on it. It will give indirect information about the status of your methylation cycle, folate metabolism, and glutathione. However, it will not tell you which B12 form would be best.

Dr. Amy Yasko offers a nutrigenomic panel, and from the results for the COMT and VDR Bsm SNPs, she determines whether hydroxo B12 or methyl B12 is better for the person. I don't know of published experimental support for this approach. She bases it on her experience.

Best regards,

Rich

 

[lampkld2]

Dr. Amy Yasko offers a nutrigenomic panel, and from the results for the COMT and VDR Bsm SNPs, she determines whether hydroxo B12 or methyl B12 is better for the person. I don't know of published experimental support for this approach. She bases it on her experience.

Best regards,

Rich

Rich,

Do you know or know where I can find the guidelines she uses with regards to this? Choosing MB12 vs HXB12 based on Snps? I have 23 and me, COMT ++, Still trying to figure out VDR.

Thanks

 

[Freddd]

I don't think that the HydroxyB12 is working for me in the SMP. I might have a slight adverse reaction to it or the fillers. I have had that reaction in the past to sublingual B12 as well. I have also had a months trial on methylB12 injections several years ago for neuropathy from Wellness Pharmacy, before SMP, without much response either way. I do suspect that B12 is important for me as I have many nervous system symptoms and have this feeling at times that my cells are starving that the methylfolate seems to address. How do I assess, make some trials about what kind of B12 to try? I will be getting the Great Plains OAT test. Will that tell me more about B12 use? Does it make sense to do that while I am a month into the SMP protocol? Or should I go off of the protocol for a short time so I have a baseline?

Hi Lucyhem,

I have also had a months trial on methylB12 injections several years ago for neuropathy from Wellness Pharmacy, before SMP, without much response either way.

A large percentage of injectable mb12 is worthless or near worthless. Many pharmacies expose it to too much light while mixing so that what you get is photolytically decomposed mb12 otherwise known as hydroxcbl. Furthyer moast people then further degrade it by exposing it to light. It should be kept in the frig wrapped in foil so it can be drawn without exposing it to light. Further the syringe must be wrapped in foil. Even if it is well protected from light about 80% of the original crystal is such that it is zero to 2 stars just like the sublingual mb12. Further if there is a missing cofactor, Metafolin about 80% of the time and including zinc, magnesium, Vit D, adb12, l-carnitine fumarate, SAM-e, TMG and maybe some others, the mb12 may be a complete non-starter. All of these may need to be in place along with A, D, E, C, POATASSIUM and others in order for mb12 to actually work. The only 2 brands of sublingual mb12 that can be counted on to work well are Jarrow and Enzymatixc Therapy and they need to be kept in tissue contact (unter tongue or lip) for 45-120 minutes or more. And one more set of things can prevent mb12/adb12/Metafolin from working; glutathione, glutathione precursors, whey (especially undenatuered), folic acid, folinic acid and for a few, vegetable food source folate. So it is a little more complicated than merely figuring out "which" b12 you need. That is a question that will almost always give you a wrong or incomplete answer just based on how it is phrased and the assumptions behind that. Most people have separate responses to each of mb12 and adb12.