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Anyone tried folic acid for overmethylation?

Bdeep86

Senior Member
Messages
278
Has anyone here ever tried using folic acid if they suspect overmethylation? Ive seen a couple practitioners that say they use this and I think a non-methylated b12. I know niacin is the go to for overmethylation, anyone know of any other supps you can use for this?
 

GhostGum

Senior Member
Messages
316
Location
Vic, AU
My doctor has diagnosed me as an over methylator and recommended folic acid but have stuck with 5-mthf, 1mg every couple of days, do not seem to tolerate it well in higher doses; so maybe I should try folic then?

So would be curious what others have to say on this.

Apparently sam-e is no good for over-methylators as well, which fits my experience for the most part.
 

PeterPositive

Senior Member
Messages
1,426
If you're an over methylator (not sure what you mean by that) why would you add a methyl donor in your system?

You should instead use a methyl "sponge" such as niacin / niacinamide which uses methyl groups in its conversion.

my 2c
 

GhostGum

Senior Member
Messages
316
Location
Vic, AU
If you're an over methylator (not sure what you mean by that) why would you add a methyl donor in your system?

You should instead use a methyl "sponge" such as niacin / niacinamide which uses methyl groups in its conversion.

my 2c

Is there such a thing as overmethylation?

I am not sure exactly what it means neither, I have been told there is no basis for it but have also been told it is simply a term to describe a sub group which display certain characteristics and has some biological basis. I assume it more likely means over activity in certain pathways and genes? I believe schizophrenia is one of the most obvious examples of potential 'over-methylation', who also more commonly display an immature or young appearance for their age. I personally very much fit some of these characteristics, along with a poorly developed and narrow jaw/facial profile.

I have also been recommended to take 500-1000mg niacinamide daily.

Most of what fits an 'over-methylator' seems to fit for me and how the supplements relate, but honestly I am well over all the subjectiveness of the subject and differences of opinion; I use what works and B12 is helping me reclaiming my life. I assume it is going to take many more years before the science around this resembles anything solid.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I am not sure exactly what it means neither, I have been told there is no basis for it but have also been told it is simply a term to describe a sub group which display certain characteristics and has some biological basis. I assume it more likely means over activity in certain pathways and genes? I believe schizophrenia is one of the most obvious examples of potential 'over-methylation', who also more commonly display an immature or young appearance for their age. I personally very much fit some of these characteristics, along with a poorly developed and narrow jaw/facial profile.

I have also been recommended to take 500-1000mg niacinamide daily.

Most of what fits an 'over-methylator' seems to fit for me and how the supplements relate, but honestly I am well over all the subjectiveness of the subject and differences of opinion; I use what works and B12 is helping me reclaiming my life. I assume it is going to take many more years before the science around this resembles anything solid.

Fair enough. But if you were overmethylating wouldn't you want to avoid folate and B12 altogether? (And maybe avoid practitioners who talk about overmethylation when there is no such thing?!!)
 

GhostGum

Senior Member
Messages
316
Location
Vic, AU
Fair enough. But if you were overmethylating wouldn't you want to avoid folate and B12 altogether? (And maybe avoid practitioners who talk about overmethylation when there is no such thing?!!)

I posed the question already that the term may refer to over regulation in certain pathways, but I just do not know the details to go into it; low histamine and excess dopamine is about all I know. I also agree the term over-methylation is a very poor one, because it suggests something very straight forward, when it is clearly far from it. Maybe the whole concept is flawed, I would like to know myself what the term is specifically referring to and why it is suppose to relate to certain characteristics.

From other posts I have seen of yours you dismiss all methylation theory and treatment anyway?
 
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Jonathan Edwards

"Gibberish"
Messages
5,256
I posed the question already that the term may refer to over regulation in certain pathways, but I just do not know the details to go into it. I also agree the term over-methylation is a very poor one, because it suggests something very straight forward, when it is clearly far from it. Maybe the whole concept is flawed, I would like to know myself what the term is specifically referring to and why it is suppose to relate to certain characteristics.

From other posts I have seen of yours you dismiss all methylation theory and treatment anyway?

I don't dismiss anything but I would like to have some coherent explanation of what 'methylation treatment' really means. The stuff I have been able to dig out on the forum does not make a lot of sense to me in biochemical terms and nobody currently contributing to the forum seems to be able to explain why it might. Vitamin B12 was the stock in trade placebo to give patients to make it seem something was being done when I was a student forty years ago. Since there do not seem to be any good trials of B12 in ME/CFS and it would be the easiest of things to do I wonder if current physicians are just continuing old practice.

On the other hand B12 deficiency is a well recognised reality and B12 is involved in methylation so there is a germ of sense there. Overmethylation sounds much less plausible and it seems back to front to treat it with any sort of B12 or folate related preparation.
 

A.B.

Senior Member
Messages
3,780
It's possible that cobalamin and folate are helpful for reasons unrelated to methylation.

For example, there is some research indicating that cobalamin protects the brain from oxidative stress and reduces inflammation.
 

GhostGum

Senior Member
Messages
316
Location
Vic, AU
I don't dismiss anything but I would like to have some coherent explanation of what 'methylation treatment' really means. The stuff I have been able to dig out on the forum does not make a lot of sense to me in biochemical terms and nobody currently contributing to the forum seems to be able to explain why it might. Vitamin B12 was the stock in trade placebo to give patients to make it seem something was being done when I was a student forty years ago. Since there do not seem to be any good trials of B12 in ME/CFS and it would be the easiest of things to do I wonder if current physicians are just continuing old practice.

On the other hand B12 deficiency is a well recognised reality and B12 is involved in methylation so there is a germ of sense there. Overmethylation sounds much less plausible and it seems back to front to treat it with any sort of B12 or folate related preparation.

And how many drugs and treatments are in the system where the underlying mechanisms are not clear? I just have no intention of throwing the baby out with the bath water because the science might not be solidly understood at this time, and I take on face value the many accounts of those with serious unknown multi-symptom disorders who recovered in the same fashion. Then you have the people who have had psychiatric disorders who's lives have changed within a couple of weeks of finding B12. And to be clear here this seldom seems to be the case, but it appears to happen.

B12 was like someone had wiped my brain with windex and cleaned all the sh*t out of my blood stream, and after 15 years of using an endless amount of supplements I can say with certainty it is no placebo, at least not for me. I should also note I actually do not tolerate folate very well, too much and I even break out in psoriasis (common in my family); but why this happens is just more speculation.

So B12 was the stock in trade placebo while anti-depressants became the foundation for reliable scientific treatment for all kinds of mood disorders?

I also do not really regard myself as ever having ME/CFS any more, but that it is clearly genetic and relating to the subject at hand somehow; this probably puts me in one of the many sub-groups.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
And how many drugs and treatments are in the system where the underlying mechanisms are not clear?

Most of them, but that is not what I was talking about. I am very happy that B12 may help some people and as AB says we may not know why and it might have nothing to do with methylation. That is quite different from people recommending treatments based on proposed mechanisms that do not seem to make sense. What I am suggesting people should be cautious about are theories of 'methylation treatment' that seem half baked. Particularly if they seem to involve the opposite of what makes any sense! The treatment may be fine (although I would like to see some reliable evidence) but not the explanation. The problem is assuming that we do know mechanisms, when as you say we often do not, and making recommendations based on theory rather than evidence.
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
On the other hand B12 deficiency is a well recognised reality and B12 is involved in methylation so there is a germ of sense there.

I was found to have a B-12 deficiency a number of years ago. I asked the doctor why and he had no idea. My impression is that many people here have a B-12 deficiency, so I thought to be clever and cite a study showing how many ME patients might have a B12 deficiency.

Surprise! There aren't any. There seems to be a number of review articles and opinion pieces that all cite each other to suggest B12 deficiency is common in our population. Only one team actually took a cursory look: Sir Simon Wessely and friends.

http://www.ncbi.nlm.nih.gov/pubmed/15016575

Autonomic function and serum erythropoietin levels in chronic fatigue syndrome.
Winkler AS1, Blair D, Marsden JT, Peters TJ, Wessely S, Cleare AJ.

Abstract

OBJECTIVE:
Given previous findings, we wished to investigate whether there was evidence of autonomic dysfunction in patients with chronic fatigue syndrome, and whether this could be related to reduced erythropoietin levels and altered red blood cell indices.

METHODS:
We assessed autonomic function and analysed blood parameters (including erythropoietin) in 22 patients with chronic fatigue syndrome who were medication-free and without comorbid depression or anxiety. Results were compared to 23 iron-deficiency anaemia patients and 18 healthy individuals.

RESULTS:
Autonomic testing in patients with chronic fatigue syndrome yielded a significantly greater increase in heart rate together with a more pronounced systolic blood pressure fall on standing compared to healthy individuals. Heart rate beat-to-beat variation on deep breathing and responses to the Valsalva manoeuvre were normal. Two of 22 patients with chronic fatigue had mild normochromic normocytic anaemia with normal ferritin, vitamin B12 and folate levels. Serum erythropoietin levels were within reference range.

CONCLUSION:
Some autonomic dysfunction is present in chronic fatigue syndrome (CFS) patients; the explanation remains uncertain, but could relate to cardiovascular deconditioning. There were no major haematological, biochemical or immunological abnormalities in these patients.

Even in a mixed cohort of chronic fatigue, ME, and who knows what else (I assume they are using the Oxford criteria) they found what looks like POTS and/or NMH (neurally mediated hypotension). But I can't make out from the abstract what they found regarding B12 levels. It state that two of 22 had normal B12, but no mention of the other 20. Doh!

(I wonder exactly what "cardiovascular deconditioning" means and if it exists/can be measured, and how it is different from plain old "deconditioning", the term I usually see.)
 
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Jonathan Edwards

"Gibberish"
Messages
5,256
I was found to have a B-12 deficiency a number of years ago. I asked the doctor why and he had no idea. My impression is that many people here have a B-12 deficiency, so I thought to be clever and cite a study showing how many ME patients might have a B12 deficiency.

Surprise! There aren't any. There seems to be a number of review articles and opinion pieces that all cite each other to suggest B12 deficiency is common in our population. Only one team actually took a cursory look: Sir Simon Wessely and friends.

This sort of basic question would be worth answering in a population based cohort. The trouble is that nobody publishes basic baseline information like this as far as I can see. I seem to remember that OMI was actually going to do a double blind B12 trial recently but I have no idea if it has got off the ground.
 

A.B.

Senior Member
Messages
3,780
Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome.

Twelve outpatients, all women, who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome were rated on 15 items of the Comprehensive Psychopathological Rating Scale (CPRS-15). These items were chosen to constitute a proper neurasthenic subscale. Blood laboratory levels were generally normal. The most obvious finding was that, in all the patients, the homocysteine (HCY) levels were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF-HCY levels and fatiguability, and the levels of CSF-B12 correlated significantly with the item of fatiguability and with CPRS-15. The correlations between vitamin B12 and clinical variables of the CPRS-scale in this study indicate that low CSF-B12 values are of clinical importance. Vitamin B12 deficiency causes a deficient remethylation of HCY and is therefore probably contributing to the increased homocysteine levels found in our patient group. We conclude that increased homocysteine levels in the central nervous system characterize patients fulfilling the criteria for both fibromyalgia and chronic fatigue syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/9310111
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome.

Good find! I wonder why it didn't turn up when I did the search. I have to say, reading PubMed is becoming an addictive hobby. I wonder what Sir Simon would say about that...
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
Vitamin B12 deficiency causes a deficient remethylation of HCY and is therefore probably contributing to the increased homocysteine levels found in our patient group

This is really interesting. I have a lab test showing elevated homocysteine and B12 at the top of the reference range. It was done several years after I started supplementing with B12. That suggests to me (in my profound ignorance) that something other than B12 is messed up in the pathways that involve homocysteine.
 

A.B.

Senior Member
Messages
3,780
This is really interesting. I have a lab test showing elevated homocysteine and B12 at the top of the reference range. It was done several years after I started supplementing with B12. That suggests to me (in my profound ignorance) that something other than B12 is messed up in the pathways that involve homocysteine.

The study is about levels in cerebrospinal fluid. It says that blood levels were generally normal. I don't think you can draw this conclusion.
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
The study is about levels in cerebrospinal fluid. It says that blood levels were generally normal. I don't think you can draw this conclusion.

Yes, of course you are correct. As soon as I poked the send button, I realized that I had overlooked a rather important fact that is right there in the title. :oops:
 
Messages
15,786
(I wonder exactly what "cardiovascular deconditioning" means and if it exists/can be measured, and how it is different from plain old "deconditioning", the term I usually see.)
It's their usual belief that sitting on our asses is what causes OI. Since we obviously couldn't actually be ill after they've been denying it for decades :rolleyes:
 

caledonia

Senior Member
The terms overmethylation and undermethylation come from Carl Pfeiffer (now deceased), and have been carried on by William Walsh (and his main practitioner Albert Mensah). These apply to mental health only and to the area of the methylation cycle containing SAMe only.

An overmethylator is treated by taking lots of methyl groups. Pfeiffer/Walsh/Mensah had originally stated to use folic acid for treatment, but Walsh/Mensah are now saying that includes any kind of folate. So that would also mean methylfolate.

An undermethylator is treated by restricting folate and instead supporting the rest of the methylation cycle. The reason is that folate creates a serotonin reuptake increase (the opposite of an SSRI). So it would make someone with serotonin/mental health issues worse.

Many people also use the terms undermethylator and overmethylator to mean a slow running cycle with blocks, or that they took too many methyl supps so the cycle is overdriven, or that methyl supps are too much for their COMT mutation or it's making CBS express so they're getting negative symptoms.

Therefore, everyone is confused because the treatment for Walsh/Mensah under and over methylation is the opposite of the more recent understanding of under and over methylation.

My best guess would be that the Walsh/Mensah undermethylation effect is caused by CBS expressing, but I can't come to any definite conclusion with the information now available.

Ben Lynch and Walsh are supposed to get together at some point and have a meeting of the minds - it would be great if they could come up with some sort of universal hypothesis that encompasses both protocols.