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B-12 - The Hidden Story

Sunday

Senior Member
Messages
733
Oh drat, forgot the methyfolate, 1 pill, can't recall dosage. Don't know if this is just brainfog or me.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
It's so interesting to me to see how this protocol works a little differently for all of us, and that we each need slightly different combinations to open the lock.

Freddd, would it make sense to get in touch with the mb12 crystal manufacturers and ask what their regimen is for handling it? You might be able to give them valuable advice and get more consistent quality. Read with interest your report on the variations.

Lena, so glad to hear you are trying again with smaller doses. I agree the nausea is wearing. My doses at this point:

adb12: 6mg
mb12: 3 mg
B-Right: 2x a day

I'm traveling so I don't have other dosages as my pills are all in one bottle, but I'm also taking:

alpha lipoic acid
l carnitine fumarate
vit D
vit E
omega 3 oils
potassium
zinc
vitamin C 2000 mg
cal/mag

and I think that's it, without my panoply of bottles I'm not sure I've got them all, will check when I get home. Good luck!


Hi Sunday,

Freddd, would it make sense to get in touch with the mb12 crystal manufacturers and ask what their regimen is for handling it? You might be able to give them valuable advice and get more consistent quality. Read with interest your report on the variations.

I've made some effort in that regard. I was assured that their packaging equipment keeps everything in the dark and that the product is packaged in opaque foil bags in small quantity or aluminimum canisters for larger amounts. As many of the experts are Japanese, to which standards the product is manufactured, and the production and engineers are Chinese and english language web pages look like sort of a literal Chinese to English translation that is tricky to understand. There are some difficulties. What I did come across was directions for taking a blood draw for testing for type of cobalamin, and that must be done with all opaque vials and syringes etc or "results will be changed". My best advice is to use a deep red safe light for fast orthochromatic film as deep red will be fully reflected by cobalamins and not absorbed causing photolytic breakdown. I am continuing to look for information.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
In doing some reading I found a medication called Neuroflax. It is made in Mexico. It is a combination of a muscle relaxant with anti-inflammatory and analgesiac characteristics (Thiocolchicoside) and adenosylcobalamin. The contents of the vial are dry and the "solvent" is injected into the vial and agitated until disolved, then drawn into the syringe and injected. The cautions for storage are to store below 25 C. and protect from light.

I still have not found any actual descriptions of the fragility of adenosylb12 in solution as this is stored dry. It reconstitues to enough for 4 injections each containing 5mg of adb12 and 1 mg of thiocolchicoside and the cost is $209.

The $10/mg of adb12 is a far cry from the 3-4 cents/mg of the Country Life.
 
S

starcycle

Guest
One issue I don't see being discussed here that I think deserves mentioning is that B12 massively stresses the adrenals. That's bad enough for some people with CFS who have functional adrenal issues, but it's even worse for those of us with thyroid disorder, especially Hashimoto's.

The cells require cortisol to be able to use thyroid hormone. With the kind of adrenal insufficiency common in CFS, that cortisol often is not available, so the T3 just ends up "pooling" and circulating in the blood, unable to get into the cell or be used properly if it does. If you get a sudden increase of cortisol -- like through stimming w/ B12 -- you can create what's known as a "thyroid dump," where that excessive circulating thyroid hormone suddenly dumps into the cell and is used, creating a temporary hyperthyroidism to various degrees.

Usually, if the amount of increased cortisol is not massive, that in itself will not pose monumental problems -- you might get a racing heart, a really bad night's sleep, or mildly get any other typical hyperthyroid symptom. But then the larger problem comes because your pituitary, signaled by the cells that now have available hormone, cranks down the TSH and your T4 production, now leaving you hypo after the initial "boost." And that can last considerably longer -- days or weeks even. And if you keep cranking up the B12, you can really crash the adrenals and end up in bad shape, with or without thyroid issues, but of course even worse if you do have thyroid disease. And around we go.

So that might preclude me and select others from following this protocol, although I haven't tried adenosyl b-12 yet to see what effects that might have. But I would guess that if the adenosyl form has more impact on muscle/fibro pain, muscle energy, and so on, that it probably taxes the adrenals even more than methyl b. And regarding methylfolate, even though I'm folate deficient, I'm also currently folate intolerant, getting a massive depression whenever I take active folate (or any folate) until it wears off. That's more neurologically induced, however, from imbalanced neurohormones, receptors, transmitters, etc. in relation to the methylation problems, because a year or two ago it used to have the opposite effect on me. It drastically lowers my heart rate, too, into the 40s. So the Country Life adenosyl b12 at least would be out, as it contains folate, though I notice that Source Naturals has a version w/out folate and that's a pretty good brand.

But it still leaves the adrenal/thyroid issues, and I'm not sure taking the higher doses of b12 required by this protocol would do much of anything but create larger problems. I tried some B12 yesterday just to get a sense of how I'm reacting to it these days, about 1/8 of a jarrow 1mg. (I've always used Jarrow methyl-B - it also might be worth mentioning that when I tried hydroxy injections a few years ago they caused a frank paranoia until they wore off after a few days - it was very scary reaction, I thought it was going to be permanent). I definitely got stimmed from the methyl b, but predictably I had terrible sleep, being up much later than usual until 2AM, waking wide awake for a few hours, and then up at 7:30. There clearly was a minor thyroid dump (feet were warmer, heart pounding a little harder, etc.)

So I'm not really sure where that all leaves me, whether I want to risk trying the adenosyl or not, whether I can do it with depressed folate levels that seem to be uncorrectable at the moment, etc. But I thought I would throw some of that out there, especially about B12 being contraindicated in some more adrenally mediated cases of CFS and in thyroid disorder. If you'retaking B12 and getting worse, some of those issues could be implicated and worth considering.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
One issue I don't see being discussed here that I think deserves mentioning is that B12 massively stresses the adrenals. That's bad enough for some people with CFS who have functional adrenal issues, but it's even worse for those of us with thyroid disorder, especially Hashimoto's.

The cells require cortisol to be able to use thyroid hormone. With the kind of adrenal insufficiency common in CFS, that cortisol often is not available, so the T3 just ends up "pooling" and circulating in the blood, unable to get into the cell or be used properly if it does. If you get a sudden increase of cortisol -- like through stimming w/ B12 -- you can create what's known as a "thyroid dump," where that excessive circulating thyroid hormone suddenly dumps into the cell and is used, creating a temporary hyperthyroidism to various degrees.

Usually, if the amount of increased cortisol is not massive, that in itself will not pose monumental problems -- you might get a racing heart, a really bad night's sleep, or mildly get any other typical hyperthyroid symptom. But then the larger problem comes because your pituitary, signaled by the cells that now have available hormone, cranks down the TSH and your T4 production, now leaving you hypo after the initial "boost." And that can last considerably longer -- days or weeks even. And if you keep cranking up the B12, you can really crash the adrenals and end up in bad shape, with or without thyroid issues, but of course even worse if you do have thyroid disease. And around we go.

So that might preclude me and select others from following this protocol, although I haven't tried adenosyl b-12 yet to see what effects that might have. But I would guess that if the adenosyl form has more impact on muscle/fibro pain, muscle energy, and so on, that it probably taxes the adrenals even more than methyl b. And regarding methylfolate, even though I'm folate deficient, I'm also currently folate intolerant, getting a massive depression whenever I take active folate (or any folate) until it wears off. That's more neurologically induced, however, from imbalanced neurohormones, receptors, transmitters, etc. in relation to the methylation problems, because a year or two ago it used to have the opposite effect on me. It drastically lowers my heart rate, too, into the 40s. So the Country Life adenosyl b12 at least would be out, as it contains folate, though I notice that Source Naturals has a version w/out folate and that's a pretty good brand.

But it still leaves the adrenal/thyroid issues, and I'm not sure taking the higher doses of b12 required by this protocol would do much of anything but create larger problems. I tried some B12 yesterday just to get a sense of how I'm reacting to it these days, about 1/8 of a jarrow 1mg. (I've always used Jarrow methyl-B - it also might be worth mentioning that when I tried hydroxy injections a few years ago they caused a frank paranoia until they wore off after a few days - it was very scary reaction, I thought it was going to be permanent). I definitely got stimmed from the methyl b, but predictably I had terrible sleep, being up much later than usual until 2AM, waking wide awake for a few hours, and then up at 7:30. There clearly was a minor thyroid dump (feet were warmer, heart pounding a little harder, etc.)

So I'm not really sure where that all leaves me, whether I want to risk trying the adenosyl or not, whether I can do it with depressed folate levels that seem to be uncorrectable at the moment, etc. But I thought I would throw some of that out there, especially about B12 being contraindicated in some more adrenally mediated cases of CFS and in thyroid disorder. If you'retaking B12 and getting worse, some of those issues could be implicated and worth considering.


Hi Starcycle,

Hypothyroid is perhaps the most frequent co-correlate of b12 deficiency and B12 deficiency is directly linked to causing Hashimotto's. There have been a number of people operating on the "thyroid" hypothesis based on the direct effects of increased energy (increased ATP production because that is one of the major jobs of b12). They tested and retested and changed doses and all sorts of things and just screwed it all up. The changes from b12 happen much faster than the the T3 and t4 and tsh tests can catch. You are feeling the most common startup effect of b12, an increase in energy. Generally people who don't overinterpret do better getting through the startup. People who have all sorts of specific explanations tend to get themselves all anxious and that complicates everything. A good percentage of what happen with b12 is that it causes faster nervous signal transmission and more signal gets through with increased performance. Whether something actually intensifies or if its appearance intensifies or some combination shoudl be considered. Mostly ity isn't what people jump on and the thyroid hypothesis has caused considerable trouble for some. Many of these changes in symptoms are phantoms that one can chase after endlessly and fruitlessly.

I don't know if your application of thyroid hypotheis on this is correct this time for you or not. All I know is that most who make changes based on the thyroid hypothesis end up not being happy with having made the changes. I am hypothyroid and have been since 8-9 years old. I had lot's of stimulation from startup with methyb12 and a lesser startup with adb12 and no real changes in thyroid at all.

And regarding Source Naturals, we tested their 5mg methylb12. It was the only brand that rated ZERO stars, no effect at all for any of the 5 hypertsensitive testers.
 
I

imgeha

Guest
thyroid / adrenal / B12

Just to record my experience. I know we're all different. I have major thyroid / adrenal problems, and take a replacement dose of both hormones. I will be on adrenal support for life. I haven't had any problems related to thyroid / adrenals since starting this protocol in September. I anticipate having to adjust my Florinef dose downwards, as my blood pressure seems a bit on the high side (despite stopping the COQ10), but I have had no raciness or symptoms of overdose. I HAVE had a big improvement in sleep and orthostatic tachycardia, and have a clearer brain and feel more optimistic.

Best

Nicola
 
S

starcycle

Guest
Just to record my experience. I know we're all different. I have major thyroid / adrenal problems, and take a replacement dose of both hormones. I will be on adrenal support for life. I haven't had any problems related to thyroid / adrenals since starting this protocol in September. I anticipate having to adjust my Florinef dose downwards, as my blood pressure seems a bit on the high side (despite stopping the COQ10), but I have had no raciness or symptoms of overdose. I HAVE had a big improvement in sleep and orthostatic tachycardia, and have a clearer brain and feel more optimistic.

Best

Nicola

So you are on hydrocortisone or some other kind of steroid? That would tend to negate any effects B12 or anything else might have on adrenal function, wouldn't it?
 
S

starcycle

Guest
Hi Starcycle,

Hypothyroid is perhaps the most frequent co-correlate of b12 deficiency and B12 deficiency is directly linked to causing Hashimotto's. There have been a number of people operating on the "thyroid" hypothesis based on the direct effects of increased energy (increased ATP production because that is one of the major jobs of b12). They tested and retested and changed doses and all sorts of things and just screwed it all up. The changes from b12 happen much faster than the the T3 and t4 and tsh tests can catch. You are feeling the most common startup effect of b12, an increase in energy. Generally people who don't overinterpret do better getting through the startup. People who have all sorts of specific explanations tend to get themselves all anxious and that complicates everything. A good percentage of what happen with b12 is that it causes faster nervous signal transmission and more signal gets through with increased performance. Whether something actually intensifies or if its appearance intensifies or some combination shoudl be considered. Mostly ity isn't what people jump on and the thyroid hypothesis has caused considerable trouble for some. Many of these changes in symptoms are phantoms that one can chase after endlessly and fruitlessly.

I don't know if your application of thyroid hypotheis on this is correct this time for you or not. All I know is that most who make changes based on the thyroid hypothesis end up not being happy with having made the changes. I am hypothyroid and have been since 8-9 years old. I had lot's of stimulation from startup with methyb12 and a lesser startup with adb12 and no real changes in thyroid at all.

And regarding Source Naturals, we tested their 5mg methylb12. It was the only brand that rated ZERO stars, no effect at all for any of the 5 hypertsensitive testers.

So Freddd - Are you saying that the B12 protocol rarely seems to work for thyroid patients, for whatever reason (their own reluctance, etc.)? Or are you saying you don't agree with their conclusion regarding B12 affecting the adrenals (and then thyroid function) in any significant way, and therefore recommend continuing?

Iow, it seems that you believe it would be worth going ahead even with the concerns I have raised, is that right? I'm just trying to get sense of whether this will be worth trying, or just has the potential to cause a worsening like so many other things.

I'm also extremely leery of pumping in that much methyl b12 with known mercury poisoning issues. Can you summarize any effects or dangers that b12, adenosyl or methyl form, is known or theorized to cause in mercury patients? I get a day-long effect from 1/8 of a tablet - I really can't imagine taking 8 of those in a day, esp. if I'm going to end up methylating a ton of mercury and causing more neuro damage.

Finally, if the Source Naturals adenosyl-b is crap and the Country Life isn't tolerated, what other brand do you recommend? I think you said there were two good ones, with CL being the best? I don't care if it's not as good, as long as it's somewhat active and doesn't contain folate.
 
I

imgeha

Guest
[So you are on hydrocortisone or some other kind of steroid? That would tend to negate any effects B12 or anything else might have on adrenal function, wouldn't it?

Yes - my adrenals were in such a bad way when I started adrenal hormone replacement my doctor did not (and does not) expect them to regain function. So I am not aiming for that. I am aiming to regain sufficient quality of life to function with and enjoy my family. I fell sick with mercury toxicity five years ago after a trip to the dentist.

Nicola
 
S

starcycle

Guest
[So you are on hydrocortisone or some other kind of steroid? That would tend to negate any effects B12 or anything else might have on adrenal function, wouldn't it?

Yes - my adrenals were in such a bad way when I started adrenal hormone replacement my doctor did not (and does not) expect them to regain function. So I am not aiming for that. I am aiming to regain sufficient quality of life to function with and enjoy my family. I fell sick with mercury toxicity five years ago after a trip to the dentist.

Nicola

Okay, well that's the point I'm making. B12 appears to stress the adrenals, but if you are on HC that's not really going to be an issue, right? ;)

About the mercury issue, though, I'm still trying to find out. I might ask on the Cutler list, see what they know about it. Unless I was sure of the effects I would be very wary indeed of taking high doses of B12 with mercury being present. That could be a recipe for a major disaster, i.e., redistributive event that could really screw up a person for life (mercury has a half life of 17-18 years in the brain. And that's for "normal" people, with properly functioning glutathione systems and functional metabolic enzymes).
 

richvank

Senior Member
Messages
2,732
One issue I don't see being discussed here that I think deserves mentioning is that B12 massively stresses the adrenals.

Hi, starcycle.

I'm very interested in this. I haven't been aware of this. Can you provide more information on it? It this based on treatment experience, or biochemical theory, or both?

One of the central issues in the treatment of CFS that several of the clinicians and researchers are debating is, where do you start? It's true that most PWCs have HPA axis dysfunction, and many have Hashimoto's thyroiditis. It's generally agreed that support for the adrenal axis should come before (or concurrently with) support for the thyroid axis. But should the adrenal axis be supported first, before anything else? And if so, should the support be things like vitamin C and vitamin B5, which the adrenals are known to need, or should it be adrenal glandular extract, or things like ginseng or licorice? Or should low-dose glucocorticoids be used?

People seem to respond differently to these various treatments. One school of thought is that adrenal and thyroid hormones should be given in an attempt to normalize these levels. Another school of thought is that there is a more fundamental metabolic problem, and that the body is compensating for it by lowering the adrenal and thyroid output, so that if they are supported first, this will cause more harm than good. Dr. Cheney has emphasized to me that if a person is in heart failure (as are many of his patients), it is not a good idea to support the thyroid first, because this will place a greater load on the heart.

I have proposed the hypothesis that a chronic partial methylation cycle block is the fundamental biochemical abnormality in CFS, and that glutathione depletion is tied to it in a vicious circle mechanism. I've suggested that the HPA axis dysfunction results from improper synthesis of ACTH by the pituitary, owing to glutathione depletion in it. I've suggested that the Hashimoto's results from damage to proteins in the thyroid by its own hydrogen peroxide, as a result of glutathione depletion in the thyroid gland, also. I've suggested that the diastolic dysfunction causing heart failure is due to glutathione depletion in the mitochondria of the heart muscle cells, lowering the rate of production of ATP. If all of this is true, then treating the partial methylation cycle block should be one of the first things to do. Perhaps 3 or 4 people have reported that their thyroid function has recovered after they started the Simplified Treatment Approach for lifting the partial methylation cycle block, in a couple of cases quite soon after starting. One person has reported that her diurnal cortisol plot returned to normal from being low after a few months on this treatment. I don't have a lot of measured data yet on this.

I recommend approaching the treatment of the methylation cycle block slowly, so that all the organs will have a chance to respond and make changes gradually. Some people have started with much smaller dosages than those suggested in the protocol of the Simplified Treatment Approach, and have been able to increase the dosages over time. The longest time anyone has been on this treatment now is nearly 3 years. For some, it has taken this long to begin to experience significant improvement, while others experienced significant improvement in a few months.

I understand the desire of people to get well as soon as possible, but I think it takes time to restore the body's function to normal if the methylation cycle has been partially blocked for an extended time. In particular, I think this has caused the detox and immune systems to be dysfunctional, and the result is accumulation of toxins and infections over time. The rate at which these can be eliminated is limited, and I think that is a major factor in slowing the recovery.

I share your concern about mercury. I'm very interested in the use of some of the newer substances for detoxing mercury. Dr. Klinghardt reports good results with MicroSilica from BioPure. People in the Yahoo OxidativeStressRelief group seem to be reporting good results with OSR#2.

Best regards,

Rich
 
S

starcycle

Guest
Hi, starcycle.

I'm very interested in this. I haven't been aware of this. Can you provide more information on it? It this based on treatment experience, or biochemical theory, or both?

Both. It's well accepted in the thyroid community that treating B12 comes last (or later, at least), after Vit. D, ferritin, etc., then adrenals, then thyroid.

One of the central issues in the treatment of CFS that several of the clinicians and researchers are debating is, where do you start?

You have to start with adrenals or else thyroid is not treatable. It's also the case that treating adrenals in some cases will be all it takes to reverse hypothyroidism. When it's a case of hashimoto's, however, that is less likely to unlikely. So one needs to supplement thyroid replacement, and that necessitates functional adrenals.

It's true that most PWCs have HPA axis dysfunction, and many have Hashimoto's thyroiditis. It's generally agreed that support for the adrenal axis should come before (or concurrently with) support for the thyroid axis. But should the adrenal axis be supported first, before anything else? And if so, should the support be things like vitamin C and vitamin B5, which the adrenals are known to need, or should it be adrenal glandular extract, or things like ginseng or licorice? Or should low-dose glucocorticoids be used?

Any and all of the above, depending on the case. Since the objective is to repair adrenal function, obviously anything that supports that is desirable, whether Vit. C, B5, licorice, cortical extract, etc. B12 is thought to stress the adrenals, and therefore is generally considered to be contraindicated until later in the process, after adrenals are strengthened.


People seem to respond differently to these various treatments. One school of thought is that adrenal and thyroid hormones should be given in an attempt to normalize these levels. Another school of thought is that there is a more fundamental metabolic problem, and that the body is compensating for it by lowering the adrenal and thyroid output, so that if they are supported first, this will cause more harm than good.

Those are valid concerns. But if a person is dying from hashimoto's disease and the attempts to fix the underlying metabolic problems have failed, there is little choice but to take the first course of action.

I have proposed the hypothesis that a partial methylation cycle block is the fundamental biochemical abnormality in CFS. If that's true, then treating it should be one of the first things to do. Perhaps 3 or 4 people have reported that their thyroid function has recovered after they started the Simplified Treatment Approach for lifting the partial methylation cycle block, in a couple of cases quite soon after starting. One person has reported that her diurnal cortisol plot returned to normal from being low after a few months on this treatment. I don't have a lot of measured data yet on this.

So what is this simplified treatment plan for the methylation block, and how does that relate to the B12 protocol?

I recommend approaching the treatment of the methylation cycle block slowly. Some people have started with much smaller dosages than those suggested in the protocol of the Simplified Treatment Approach, and have been able to increase the dosages over time. The longest time anyone has been on this treatment now is nearly 3 years. For some, it has taken this long to begin to experience significant improvement, while others experienced significant improvement in a few months.

I share your concern about mercury. I'm very interested in the use of some of the newer substances for detoxing mercury. Dr. Klinghardt reports good results with MicroSilica from BioPure. People in the Yahoo OxidativeStressRelief group seem to be reporting good results with OSR#2.

That is good to know, since microsilica sounds relatively low toxic (although I haven't specifically researched this OSR#2 you mention yet). But that is quite a change from klinghart's earlier DMPS regimen that almost literally killed a few people I know. So it's good to see he is hopefully mending his ways, as he was a very dangerous guy in the past, at least.
 

richvank

Senior Member
Messages
2,732
So what is this simplified treatment plan for the methylation block, and how does that relate to the B12 protocol?

Hi, Starcycle.

Here's the current version of the protocol for the Simplified Treatment Approach. It differs from the protocol freddd has proposed principally in the form of B12 and in the dosages, but the essence is simultaneous support for B12 and reduced forms of folate, as well as vitamin and mineral cofactors for the enzymes in the methylation cycle and associated biochemical pathways. This is essentially the same protocol that was used in the clinical study conducted by Neil Nathan, M.D., which we reported at the IACFS/ME conference last March in Reno.

I recommend that the Vitamin Diagnostics, Inc., methylation pathways panel be run first, to determine whether there is a partial methylation cycle block, and to establish baseline values to evaluate the progress of treatment later on. This panel will be available hopefully starting again at about the end of January, since the lab is undergoing a move to another building. Contact information for this panel and comments on interpreting it are pasted below.

Rich


April 18, 2009


SIMPLIFIED TREATMENT APPROACH
FOR LIFTING THE METHYLATION CYCLE BLOCK
IN CHRONIC FATIGUE SYNDROME (Revised)

(Extracted from the full treatment program
developed by Amy Yasko, Ph.D., N.D.
which is used primarily in treating autism [1])

SUPPLEMENTS

1. FolaPro [2]: ¼ tablet (200mcg) daily
2. Actifolate [3]: ¼ tablet daily
3. General Vitamin Neurological Health Formula [4]: start with ¼ tablet and work up dosage as tolerated to 2 tablets daily
4. Phosphatidyl Serine Complex [5]: 1 softgel capsule daily
5. Activated B12 Guard [6]: 1 sublingual lozenge daily

All these supplements can be obtained from http://www.holisticheal.com, or all but the third one can be obtained from other sources.
The first two supplement tablets are difficult to break into quarters. We recommend that you obtain (from any pharmacy) a good-quality pill splitter to assist with this process. They can, alternatively, be crushed into powders, which are then separated on a flat surface using a knife or single-edged razor blade, and the powders can be mixed together. They can be taken orally with water, with or without food.
These supplements can make some patients sleepy, so in those cases they take them at bedtime. They can be taken at any time of day, with or without food.
GO SLOWLY. As the methylation cycle block is lifted, toxins are released and processed by the body, and this can lead to an exacerbation of symptoms. IF THIS HAPPENS, try smaller doses, every other day. SLOWLY work up to the full dosages.
Although this treatment approach consists only of nonprescription nutritional supplements, a few patients have reported adverse effects while on it. Therefore, it is necessary that patients be supervised by physicians while receiving this treatment.


[1] Yasko, Amy, and Gordon, Garry, The Puzzle of Autism, Matrix Development Publishing, Payson, AZ, 2006, p. 49.
[2] FolaPro is a registered trademark of Metagenics, Inc.
[3] Actifolate is a registered trademark of Metagenics, Inc.
[4] General Vitamin Neurological Health Formula is formulated and supplied by Holistic Health Consultants LLC.
[5] Phosphatidyl Serine Complex is a product of Vitamin Discount Center.
[6] Activated B12 Guard is a registered trademark of Perque LLC.


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 costs $300 and requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on your clinician’s letterhead.


Available from:

Vitamin Diagnostics, Inc.
540 Bordentown Avenue
South Amboy, NJ 08879
USA
Phone:+1 (732) 721-1234


Lab Director: Tapan Audhya, Ph.D.
(usually at the lab on Tues. and Wed. from 1 to 3 p.m., Eastern time)

Dr. Audhya is willing to help clinicians with interpretation of the panel by phone.


Interpretation of the Vitamin Diagnostics
Methylation Pathways Panel

by
Rich Van Konynenburg, Ph.D.


Several people have asked for help in interpreting the results of
their Vitamin Diagnostics, Inc., methylation pathway panels. Here are my
suggestions for doing so. They are based on my study of the
biochemistry involved, on my own experience with interpreting more
than 120 of these panel results to date, and on discussion of some of
the issues with Tapan Audhya, Ph.D., who is the director of the
Vitamin Diagnostics lab.

The panel consists of measurement of two forms of glutathione
(reduced and oxidized), adenosine, S-adenosylmethionine (SAM) , S-
adenosylhomocysteine (SAH), and seven folic acid derivatives or
vitamers.

According to Dr. Audhya, the reference ranges for each of these
metabolites was derived from measurements on at least 120 healthy
male and female volunteer medical students from ages 20 to 40, non-
smoking, and with no known chronic diseases. The reference ranges
extend to plus and minus two standard deviations from the mean of
these measurements.

Glutathione: This is a measurement of the concentration of the
reduced (active) form of glutathione (abbreviated GSH) in the blood
plasma. From what I've seen, most people with chronic fatigue
syndrome (PWCs) have values below the reference range. This means
that they are suffering from glutathione depletion. As they undergo
the simplified treatment approach to lift the methylation cycle
block, this value usually rises into the normal range over a period
of months. I believe that this is very important, because if
glutathione is low, vitamin B12 is likely unprotected and reacts with toxins
that build up in the absence of sufficient glutathione to take them
out. Vitamin B12 is thus “hijacked,” and not enough of it is able to
convert to methylcobalamin, which is what the methylation cycle needs
in order to function normally. Also, many of the abnormalities and
symptoms in CFS can be traced to glutathione depletion.

Glutathione (oxidized): This is a measurement of the concentration
of the oxidized form of glutathione (abbreviated GSSG) in the blood
plasma. In many (but not all) PWCs, it is elevated above the normal
range, and this represents oxidative stress.

Adenosine: This is a measure of the concentration of adenosine in the
blood plasma. Adenosine is a product of the reaction that converts
SAH to homocysteine. In some PWCs it is high, in some it is low, and
in some it is in the reference range. I don't yet understand what
controls the adenosine level, and I suspect there is more than one
factor involved. In most PWCs who started with abnormal values, the
adenosine level appears to be moving into the reference range with
methylation cycle treatment, but more data are needed.

S-adenosymethionine (RBC) (SAM): This is a measure of the
concentration of SAM in the red blood cells. Most PWCs have values
below the reference range, and treatment raises the value. S-
adenosylmethionine is the main supplier of methyl groups in the body,
and many biochemical reactions depend on it for their methyl
groups. A low value for SAM represents low methylation capacity, and
in CFS, it appears to result from a partial block at the enzyme methionine
synthase. Many of the abnormalities in CFS can be tied to lack of
sufficient methyation capacity.

S-adenosylhomocysteine (RBC) (SAH): This is a measure of the
concentration of SAH in the red blood cells. In CFS, its value
ranges from below the reference range, to within the reference range,
to above the reference range. Values appear to be converging toward
the reference range with treatment. SAH is the product of reactions
in which SAM donates methyl groups to other molecules.

Sum of SAM and SAH: When the sum of SAM and SAH is below 268
micromoles per deciliter, it appears to suggest the presence of
upregulating polymorphisms in the cystathione beta synthase (CBS)
enzyme, though this may not be true in every case.

Ratio of SAM to SAH: A ratio less than about 4.5 also represents low
methylation capacity. Both the concentration of SAM and the ratio of
concentrations of SAM to SAH are important in determining the
methylation capacity.

5-CH3-THF: This is a measure of the concentration of 5-methyl
tetrahydrofolate in the blood plasma. It is normally the most
abundant form of folate in the blood plasma. It is the form that
serves as a reactant for the enzyme methionine synthase, and is thus
the most important form for the methylation cycle. Many PWCs have a
low value, consistent with a partial block in the methylation cycle.
The simplified treatment approach includes FolaPro, which is
commercially produced 5-CH3-THF, so that when this treatment is used,
this value rises in nearly every PWC. If the concentration of 5-CH3-
THF is within the reference range, but either SAM or the ratio of SAM
to SAH is below the reference values, it suggests that there is a
partial methylation cycle block and that it is caused by
unavailability of sufficient bioactive B12, rather than
unavailability of sufficient folate. I have seen this frequently,
and I think it demonstrates that the “hijacking” of B12 is the root
cause of most cases of partial methylation cycle block. Usually
glutathione is low in these cases, which is consistent with lack of
protection for B12, as well as with toxin buildup.

10-Formyl-THF: This is a measure of the concentration of 10-formyl
tetrahydrofolate in the blood plasma. It is usually on the low side in PWCs.
This form of folate is involved in reactions to form purines, which
form part of RNA and DNA as well as ATP.

5-Formyl-THF: This is a measure of the concentration of 5-formyl
tetrahydrofolate (also called folinic acid) in the blood plasma.
Most but not all PWCs have a value on the low side. This form is not used
directly as a substrate in one-carbon transfer reactions, but it can
be converted into other forms of folate. It is one of the
supplements in the simplified treatment approach, which helps to
build up various other forms of folate.

THF: This is a measure of the concentration of tetrahydrofolate in
the blood plasma. In PWCs it is lower than the mean normal value of 3.7
nanomoles per liter in most but not all PWCs. This is the
fundamental chemically reduced form of folate from which several
other reduced folate forms are made. The supplement folic acid is
converted into THF by two sequential reactions catalyzed by
dihydrofolate reductase (DHFR). THF is also a product of the
reaction of the methionine synthase enzyme, and it is a reactant in
the reaction that converts formiminoglutamate (figlu) into
glutamate. If figlu is high in the Genova Diagnostics Metabolic
Analysis Profile, it indicates that THF is low.

Folic acid: This is a measure of the concentration of folic acid in
the blood plasma. Low values suggest folic acid deficiency in the
current diet. High values are sometimes associated with inability to
convert folic acid into other forms of folate, such as because of
polymorphisms in the DHFR enzyme. They may also be due to high
supplementation of folic acid.

Folinic acid (WB): This is a measure of the concentration of folinic
acid in the whole blood. See comments on 5-formyl-THF above. It
usually tracks with the plasma 5-formyl-THF concentration.

Folic acid (RBC): This is a measure of the concentration of folic
acid in the red blood cells. The red blood cells import folic acid
when they are initially being formed, but during most of their
approximately four-month life, they do not normally import, export, or use
it. They simply serve as reservoirs for it, giving it up when they
are broken down. Many PWCs have low values. This can be
caused by a low folic acid status in the diet over the previous few
months, since the population of RBCs at any time has ages ranging
from zero to about four months. However, in CFS it can also be
caused by damage to the cell membranes, which allows folic acid to
leak out of the cells. Dr. Audhya reports that treatment with omega-
3 fatty acids can raise this value over time.
 

richvank

Senior Member
Messages
2,732
To starcycle re: B12 and adrenals

quote from starcycle:

"It's well accepted in the thyroid community that treating B12 comes last (or later, at least), after Vit. D, ferritin, etc., then adrenals, then thyroid."

Hi, starcycle.

I wonder if the "thyroid community" believes B12 supplementation must come after adrenal and thyroid support for people who have Hashimoto's thyroiditis and HPA axis dysfunction as part of CFS, or does it apply only to non-CFS thyroid and adrenal cases?

My concern is that the methylation cycle is present in all types of cells, including those of the thyroid and adrenals. If this cycle is not supported first, I don't see how these organs will recover their function.

Rich
 
S

starcycle

Guest
Hi, Starcycle.

Here's the current version of the protocol for the Simplified Treatment Approach.

I am completely intolerant to the smallest amount of folate (like even at 1-10mcg level), and phosphatidyl serine completely messed up my HPAA a number of years ago (and reportedly changed my personality in some ways, according to friends). I have no idea what's in GVNHF, but based on my intolerance to most things (including most of the B vitamins) I'm guessing that would not be possible for me to take, either. Omega-3s have the opposite effect in me and cause inflammation, raising my liver enzymes and causing noticeable pains in my neck and left-side vasculature. So it looks like that takes care of that protocol. ;)

The methylation pathways test still looks like it would be very interesting to have, but my integrative doctor left the area recently, and then I became basically homebound a few weeks ago with the full-blown CFS crash. So I am not optimistic about finding a local doctor to do the test, if I could even get there. If a chiropractor can order one, I might be able to do that eventually. So thanks for the information at least. I already know I am folate deficient by mainstream medical lab standards, so there is probably little doubt that this test would reveal some more problems in deeper or broader focus.


I wonder if the "thyroid community" believes B12 supplementation must come after adrenal and thyroid support for people who have Hashimoto's thyroiditis and HPA axis dysfunction as part of CFS, or does it apply only to non-CFS thyroid and adrenal cases?

My concern is that the methylation cycle is present in all types of cells, including those of the thyroid and adrenals. If this cycle is not supported first, I don't see how these organs will recover their function.

I think it's generally understood that B12 needs to come after becoming stabilized on thyroid in all people who are intolerant to thyroid hormone because of adrenal dysfunction. If anything, it would seem to apply more to CFS thyroid cases than non-CFS cases, if that's what you're asking.
 

JanisB

Senior Member
Messages
247
Location
Central Ohio
I tried 5 mg of methyl B12 for about 2 months as well as 3 mg of adenosyl. When I tested plasma aminos, my methylation cycle was stuck at methionine. And nothing was going down the transulfuration pathway to cystathionine either. Rich thought the methyl B12 could be speeding it up too much, yet my organic acid testing showed that I needed more folate and more B12. In previous tests (before introducing the methyl and adenosyl B12), my tests showed adequate folate and a mild need for B12.

The point I'm making, through my rambling fogged brain, is that taking high amounts of methyl B12 can mess things up for some of us.

Much better to test than to screw up your physiology. The impact on my methylation led to liver problems for me, like high enzymes (AST, ALT), inadequate bile production experienced as inability to digest a high fat meal (an omelet with a little cheese and avocado) which previously had been no problem.
 
I

imgeha

Guest
Okay, well that's the point I'm making. B12 appears to stress the adrenals, but if you are on HC that's not really going to be an issue, right? ;)

About the mercury issue, though, I'm still trying to find out. I might ask on the Cutler list, see what they know about it. Unless I was sure of the effects I would be very wary indeed of taking high doses of B12 with mercury being present. That could be a recipe for a major disaster, i.e., redistributive event that could really screw up a person for life (mercury has a half life of 17-18 years in the brain. And that's for "normal" people, with properly functioning glutathione systems and functional metabolic enzymes).


The answer you will get on the Cutler list is that B12 doesn't methylate mercury to any meaningful extent, and that some people need lots of B12. I did over 100 rounds of DMSA / ALA before starting this protocol to reduce body burden, but have still had 3 big herxes since September, and have felt much better since. I could barely tolerate the folate either - even 1/4 tablet made me feel unbearably tired and draggy. I have now worked up to 2 tablets and have much more energetic and optimistic. In my experience the things you react most to are the things you need the most.

Nicola
 
S

starcycle

Guest
Hi Janis - did you do the Vitamin Diagnostics test? Or was it some other test that found the blockages?

Thanks for the report - I am very leery of screwing myself up any more than has already been done by taking supplements "blindly." I wish I hadn't taken half the things I have that were touted as "the cure." Messing up some of these deep-seated pathways can have long-lasting effects, so pre/caution is definitely in order!
 
S

starcycle

Guest
The answer you will get on the Cutler list is that B12 doesn't methylate mercury to any meaningful extent, and that some people need lots of B12. I did over 100 rounds of DMSA / ALA before starting this protocol to reduce body burden, but have still had 3 big herxes since September, and have felt much better since. I could barely tolerate the folate either - even 1/4 tablet made me feel unbearably tired and draggy. I have now worked up to 2 tablets and have much more energetic and optimistic. In my experience the things you react most to are the things you need the most.

Nicola

Thanks! That answers the mercury question. I also tend to agree with the idea of reacting to things you need -- I react with obvious and definite symptoms even to *homeopathic* adrenal remedies! But there's nothing in there! And yet I react! mind = blown! :eek: :p
 
I

imgeha

Guest
I tried 5 mg of methyl B12 for about 2 months as well as 3 mg of adenosyl. When I tested plasma aminos, my methylation cycle was stuck at methionine. And nothing was going down the transulfuration pathway to cystathionine either. Rich thought the methyl B12 could be speeding it up too much, yet my organic acid testing showed that I needed more folate and more B12. In previous tests (before introducing the methyl and adenosyl B12), my tests showed adequate folate and a mild need for B12.

The point I'm making, through my rambling fogged brain, is that taking high amounts of methyl B12 can mess things up for some of us.

Much better to test than to screw up your physiology. The impact on my methylation led to liver problems for me, like high enzymes (AST, ALT), inadequate bile production experienced as inability to digest a high fat meal (an omelet with a little cheese and avocado) which previously had been no problem.


Hi, Janis

OMG - I have just spent Christmas with gallbladder problems - indigestion, backache, pain and nausea - seemingly out of the blue. I did blood tests but there was no inflammation, no infection, no high LFTS - so my doctor is stumped. I had upped my B12 to 10g shortly before it started. I stopped all B12s except the folate, but have recently reintroduced mB12 at 1g.

Why would too much mB12 and possible over-methylation lead to inadequate bile production / gallbladder problems? I had no detectable liver problems - at least none that showed up on tests. I had put it down to coincidence, but now you have got me wondering.... :confused:

In your case, what supplement do you have to take to complete the methylation cycle?

Nicola