B-12 - The Hidden Story

hixxy

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I have not had any recent b12/folate serology done. But my last ones were early last year at:

Serum B12: 760.00
R/C Folate: 2036.00

I do not remember in months leading up to this I did do some hydroxob12 injections 1000mcg and some cyanocobalamin lozeneges erk. So that may be responsible for the high normal b12.

These were ceased 2 months before testing though.

Fredd: Do you have somewhere I can send you a pathology spreadsheet done up by my previous doctor I can no longer afford to see? You may find some of it quite interesting.

I'm in the process of putting $$ aside to go back to this doctor. He seems to be the only doctor I know in my part of Australia with half a clue.

hixxy.
 

richvank

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Hi, all.

I just want to note again that in ME/CFS the serum B12 and serum folate levels are often found to be in the normal ranges or above the normal ranges. This does not mean that they are being used properly by the cells, and in fact, it can mean the opposite of that.

There is considerable evidence that in ME/CFS there is a functional (as opposed to an absolute) deficiency of B12, due to glutathione depletion. This leads to a partial block of the enzyme methionine synthase, which links the methylation cycle and the folate metabolism. When this enzyme becomes partially blocked, it impacts both both of them negatively. The methyl trap mechanism channels other folates in the cells into methylfolate, and the elevated peroxynitrite (due to glutathione depletion and oxidative stress) breaks down the intracellular methylfolate.

The result of this is that the cells are not able to use either B12 or folate properly. The serum levels do not reflect this problem, and they are the wrong tests to run in ME/CFS. They will show if there are absolute deficiencies of B12 or folate, but these are not the issues in most cases of ME/CFS. A better indication of the B12 status can be gotten from a measurement of urine methylmalonate. A better indication of the folate status can be gotten from a measurement of urine formiminoglutamate ("Figlu"). Both are measured in either the Genova Diagnostics or the Metametrix urine organic acids panels.

In ME/CFS, an even better panel is the methylation pathways panel offered by the Health Diagnostics and Research Institute in the U.S. and the European Laboratory of Nutrients in the Netherlands. This panel gives direct information about the status of glutathione, the methylation cycle and the folate metabolism.

Best regards,

Rich
 

xrunner

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In ME/CFS, an even better panel is the methylation pathways panel offered by the Health Diagnostics and Research Institute in the U.S. and the European Laboratory of Nutrients in the Netherlands. This panel gives direct information about the status of glutathione, the methylation cycle and the folate metabolism.

Best regards,
Rich
Hi Rich,
how important is it to know the status of glutathione to assess how methylation works?
I've recently discovered that the methylation panel of the ELN is not the same as the one in the US. They don't include any measure of glutathione just methylcobalamin.
Is MB12 a good proxy?
I was quite disappointed as I got mixed messages from my panel and was looking for some indication of glutathione levels to assess where I am with regard to methylation but I was told they don't include any in the European panel.
I think anybody who goes for the ELN panel should know in advance they'll have to request glutathione separately.
 

hixxy

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Hi, all.

I just want to note again that in ME/CFS the serum B12 and serum folate levels are often found to be in the normal ranges or above the normal ranges. This does not mean that they are being used properly by the cells, and in fact, it can mean the opposite of that.

There is considerable evidence that in ME/CFS there is a functional (as opposed to an absolute) deficiency of B12, due to glutathione depletion. This leads to a partial block of the enzyme methionine synthase, which links the methylation cycle and the folate metabolism. When this enzyme becomes partially blocked, it impacts both both of them negatively. The methyl trap mechanism channels other folates in the cells into methylfolate, and the elevated peroxynitrite (due to glutathione depletion and oxidative stress) breaks down the intracellular methylfolate.

The result of this is that the cells are not able to use either B12 or folate properly. The serum levels do not reflect this problem, and they are the wrong tests to run in ME/CFS. They will show if there are absolute deficiencies of B12 or folate, but these are not the issues in most cases of ME/CFS. A better indication of the B12 status can be gotten from a measurement of urine methylmalonate. A better indication of the folate status can be gotten from a measurement of urine formiminoglutamate ("Figlu"). Both are measured in either the Genova Diagnostics or the Metametrix urine organic acids panels.

In ME/CFS, an even better panel is the methylation pathways panel offered by the Health Diagnostics and Research Institute in the U.S. and the European Laboratory of Nutrients in the Netherlands. This panel gives direct information about the status of glutathione, the methylation cycle and the folate metabolism.

Best regards,

Rich
I've been told twice now from doctors that having a OAT test done when you're under extreme malnutrition provides grossly inaccurate results (This happened to me start of last year when I was wasting away rapidly, god knows why the doctors ordered it).

Do you know if this would affect methylmalonate and figlu results too?

I'm going to give Health Diagnostics and Research Institute a call before the end of the week to enquire about the logistics of having the methylation panel done from Australia. No doubt there is a time limit on getting the samples back to the lab for processing. I live in a remote area because of MCS and suspect that freighting it from (at a reasonable price) to the lab in US in a reasonable time frame won't be possible.

I truely wish this lab would get a web presence or at least an email they are contactable by. Would make things a lot easier.

hixxy
 

richvank

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Hi Rich,
how important is it to know the status of glutathione to assess how methylation works?
I've recently discovered that the methylation panel of the ELN is not the same as the one in the US. They don't include any measure of glutathione just methylcobalamin.
Is MB12 a good proxy?
I was quite disappointed as I got mixed messages from my panel and was looking for some indication of glutathione levels to assess where I am with regard to methylation but I was told they don't include any in the European panel.
I think anybody who goes for the ELN panel should know in advance they'll have to request glutathione separately.
Hi, xrunner.

I was also disappointed recently to learn that ELN is not including glutathione routinely in their panel. No, I don't think that methylcobalamin is a good proxy, because most of the methylcobalamin in the blood is bound to haptocorrin, not to transcobalamin, and is not available to other than liver cells.

I may see the owner of ELN this weekend, since he usually comes to the Orthomolecular Health Medicine Society meeting. If so, I will certainly raise this issue with him.

Best regards,

Rich
 

richvank

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Hi, hixxy.

The OAT test results are certainly affected by malnutrition. I don't know that I would characterize the results as inaccurate in that case. I think they reflect what is going on in the metabolism, which has problems when a person is malnourished. It requires some interpretation to understand the results, because the metabolism is a highly interactive system. For examples, if a person is very low in branched-chain amino acids or in B6 or B2, methylmalonate may be low, even though there is also a functional B12 deficiency. And if histamine is very low, figlu may be low even though there is a deficiency of tetrahydrofolate. So yes, it does make it difficult to use these indirect markers to determine whether there is a partial methylation cycle block or not.

People do send samples to Health Diagnostics from Australia, but they have to go out via FedEx with an ice pack (ordinary water ice, not dry ice), and this is possible only from the larger cities, I understand. The sample vials have enzyme blockers in them that will keep the samples in usable condition for probably more than 48 hours, but I think the lab specifies 48 hours.

Best regards,

Rich
 

hixxy

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Interesting, I had a severe protein depletion state (major muscle wasting) and suffer pyroluria (major b6 deficiency) and according to my doctor I was B2 deficiency.

I live on an island 50 mins from the nearest major CBD. I may have to get my carer to take the sample back to the mainland and drop it at a depo. I guess that would solve the problem.
 

Little Bluestem

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As for P5P, I wouldn't start it yet. Unless your BHMT/CBS/NOS is controlled, I don't care what anyone says, the P5P will only drive the CBS harder. Autistics need it but can"t handle it until this happens either. I have seen it with my own kids as well as time and time again with others. In this instance, I believe Yasko is right. She sure isn't right about everything though, there are other ways to get there.

Angela
Can someone give me the "For Dummys" version of what BHMT/CBS/NOS is and how I know if it is controlled.

I am reading through this thread with the plan of starting the active Bs protocol. I very recently started taking P5P on the advice of a dietitian who know nothing about ME/CFS. Now I am wondering if I should be taking it.
 

brenda

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Rydra

I can`t find the post where you suggested coQ10 but I did some reading and found that ubiquinone which is the one I took, may not be suitable and ubiquinol should be used instead so I took my first 100mg today and within 2 hours the reductionin pain levels in my body is amazing. I have been in a great deal of pain for a long time and this is the first relief I have had apart from accupuncture which unfortunately boosted my immune system which is not what I wanted with autoimmune disease.

I feel a bit spaced out but I don`t mind that. I must have been seriously depleted of coQ10.

I also started vit E and hope to start the protocol in a few days with one quarter of active B complex minus folic acid. Thanks.

Best wishes
Brenda
 

Freddd

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Sorry, but I've read this first post about a dozen times and still can't figure out what to start out with and dosages. Can someone help me?

EDIT: I think I figured out that to start there are 7 supplements:
1. Jarrow B12
2. Enzymatic B12
3. Solgar Metafolin
4. Dibencozide
5. B-complex with Metafolin
6. Potassium
7. omega 3's

However, still not sure about dosage.

Thanks!
First there are the basics, things like, A, B-complex with Metafolin (twice a day), C, D, E, calcium, magnesium, zinc (titrate to 50mg), misc minerals, selenium chromium, omega3s (2000mg of DHA, EPA), lecithin.

Potassium should be on hand because as soon as methylation starts, potassium drops for most people and you will very likely need it. See the discussions on the menu and read some. You may need as much as 2000mg or so per day of potassium by titration in relief of low potassium symptoms.

A single 1mg Enzymatic Therapy per day is quite adequate for most preople to start with. After a week, add dibencozide at least once a week. The Jarrow 5mg comes later as you step up the dose and when you go for maximum effectivness you will need both brands.
 

greenshots

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They each have certian functions and when they have defects, especially together, there tend to be problems,

The BHMT is the short cut in the methylation cycle. It converts homocysteine into a useable methyl group and when its blocked, homocysteine levels go up. Most people with these BHMT blocks have ADD (more nor epi to dopamine levels) and/or gut issues.

The CBS is that hole in the bucket that can drain the cycle faster. This means everything good and bad can drain out too fast and make toxic ammonia and sulfites. this tends to lead to an overload on the urea cycle and can lead to triggering of fight or flight which is the beginning of adrenal fatigue (esp with the ACE defect!)

The NOS is the clean up guy in the urea cycle (waste cycle) and he also makes nitric oxide to widen blood vessels and keep them free of plaques. This cycle borrows BH4 from the MTHFR A1298C and if you have a partially or fully blocked A1298C, you really have waste build up!

The cycle is interwoven so that nothing happens in isolation. One issue leads to another and another.

Since P5P amps up the CBS and affects the COMT (I don't know why it affects the COMT) using it before your ready can cause problems even while it helps others.

Angela



Can someone give me the "For Dummys" version of what BHMT/CBS/NOS is and how I know if it is controlled.

I am reading through this thread with the plan of starting the active Bs protocol. I very recently started taking P5P on the advice of a dietitian who know nothing about ME/CFS. Now I am wondering if I should be taking it.
 
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Dear Fredd,

In an earlier reply about this protocol and how to start with it you had replied

"Metafolin daily, Jarrow mb12 5mg daily, the ET 1mg can wait until you see if you need a little more help, Source Naturals Dibencozide, half a tablet twice a week is probably fine. Things may need adjustment later after everything is running smoothly."

I just saw to someone else who asked you a similar question you replied

"First there are the basics, things like, A, B-complex with Metafolin (twice a day), C, D, E, calcium, magnesium, zinc (titrate to 50mg), misc minerals, selenium chromium, omega3s (2000mg of DHA, EPA), lecithin.

Potassium should be on hand because as soon as methylation starts, potassium drops for most people and you will very likely need it. See the discussions on the menu and read some. You may need as much as 2000mg or so per day of potassium by titration in relief of low potassium symptoms.

A single 1mg Enzymatic Therapy per day is quite adequate for most preople to start with. After a week, add dibencozide at least once a week. The Jarrow 5mg comes later as you step up the dose and when you go for maximum effectivness you will need both brands."


There seems to be some conflict in both the advices you have given ?


Regards,
Deepak
 

Rand56

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While we are talking about the basic supplements, I have a question in particular to the supps A,C,D,E, calcium, magnesium,zinc,selenium, chromium, and omega 3's and I apologize in advance if my question has already been addressed in another thread.

Does anyone more knowledgeable know if any of these supps I just listed lower cortisol? I have lower baseline cortisol and I already know that atleast high dose C and high dose fish oil can lower cortisol. I feel worse when taking higher doses on both of these. As a matter of fact, I just stopped taking my daily lower dose of fish oil just a few days ago and I feel better. Maybe a coincidence but maybe I just have a negative reaction to any dose of fish oil. I also read where high dose zinc can lower cortisol.

There might be more people on here with high cortisol but I am sure there are some who have low cortisol as well. As for me, I am not in a position to spend the bucks on constantly monitoring my saliva cortisol levels and trial different doses of supps to see which ones and at what dose have negative effects on me. I just have to go by trial and error on my own according to my symptoms. What is hard to determine is if I feel worse am I have a "healing" type symptom or am I just feeling worse from lowering my cortisol levels too low? Anyone have any input on this?
 

Rand56

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AFAIK, vitamin C and fish oil (EPA) are the only supps in the protocol that lower cortisol.
hi Adreno

Thanks for your input. Funny you mention the fish oil as the EPA having this effect. The brand I am taking is the Minami Nutrition MorDHA which only has 63mg of EPA in it. I was taking more of this previously along with other fish oil when I felt absolutely horrible on it. That's when I cut back down to only 1 per day of the MorDHA. But even when I stopped this a few days ago I felt better. Maybe it is a coincidence and maybe me feeling somewhat better was from another factor. Maybe I'll give it a break for a few more days and add 1 back in to see if it negatively effects me or not. Don't want to totally forget about the positives from it and maybe I'd be ok on just taking it a couple times a week instead of daily.
 

adreno

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hi Adreno

Thanks for your input. Funny you mention the fish oil as the EPA having this effect. The brand I am taking is the Minami Nutrition MorDHA which only has 63mg of EPA in it. I was taking more of this previously along with other fish oil when I felt absolutely horrible on it. That's when I cut back down to only 1 per day of the MorDHA. But even when I stopped this a few days ago I felt better. Maybe it is a coincidence and maybe me feeling somewhat better was from another factor. Maybe I'll give it a break for a few more days and add 1 back in to see if it negatively effects me or not. Don't want to totally forget about the positives from it and maybe I'd be ok on just taking it a couple times a week instead of daily.
Well, according to the research, EPA has suppressive effects on cortisol, whereas DHA hasn't. So if you're feeling bad from taking DHA it's not from a lowering of cortisol. EPA is also what gives fish oil its mood boosting effects, whereas DHA has more nootropic effects.
 

adreno

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This is where I read about zinc lowering cortisol. I don't know if this was from a large enough sample to make this study all that legit but atleast it did conclude that from 25mg of zinc, it did lower cortisol. The first post on this site someone pasted this study......

http://www.realthyroidhelp.com/forums/viewtopic.php?f=2&t=5804
Yeah, I see that. Never knew that before. Maybe it's connected to zinc's effects on testosterone. Most men are deficient in zinc, but it could be prudent not to go over 15mg daily in this case.
 

Rand56

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Yeah, I see that. Never knew that before. Maybe it's connected to zinc's effects on testosterone. Most men are deficient in zinc, but it could be prudent not to go over 15mg daily in this case.
Yeah and I wonder if this has anything to do with what I have heard that it's better to take it at night so you don't lower cortisol too much by taking it in the morning when you need cortisol at it's highest peak. Who knows but in any event..might be best for me to lower it to 15mg like you say. I have been taking 30mg of OptiZinc.
 

adreno

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Yeah and I wonder if this has anything to do with what I have heard that it's better to take it at night so you don't lower cortisol too much by taking it in the morning when you need cortisol at it's highest peak. Who knows but in any event..might be best for me to lower it to 15mg like you say. I have been taking 30mg of OptiZinc.
Makes sense. Zinc has a half life of <14 hours, so if you take it with your evening meal, you should be good to go in the morning. You might want to supplement with zinc lozenges in case of a flu or cold.