For those of you who don’t know me on the forums, I am a 40 years old and have been dealing with some type of Idiopathic Neuropathy for the past two years. I’ve been trying a lot of different meds, vitamins, and tests to figure out what’s going on with me. Aside from a lumbar puncture that showed a slight protein elevation all other tests came up empty. Funny thing was I always felt tired my whole life, lack of energy. I had Mono and EPV between 18-28 years old. In my 30’s I exercised, ate healthy and felt great. Never got sick or felt tired. At around 35, I started to eat junk again but never got sick or felt run down It seemed eating health jumpstarted my immune system. By 36 I had LPR reflux and started on Nexium (PPI). At 38 years old is when it all happened. Started with tightness in throat for 6 months, then burning in chest for 9 months and then burning moved to my back. It sucks because my upper back, lower neck area is sensitive to touch (Allodynia) and its causes a lot of pain. I don’t have any motor or autonomic issues, strictly sensory. I decided to get a 23andme test kit and uploaded my data to http://geneticgenie.org/methylation-analysis/ and gave me the attached readings.



COM V158 +/+ Says not to take a lot of Methyl supplements
MTHFR C667T +/- and MTHFR A1298C +/-Both C667T and A1298C according to Benjamin Lynch, says its bad to have both +/- and one needs Methyl Folic Acid
MTRR A66G +/+ Recommends Methyl-B12 (Been taking 1000mg) for a year now
MAO AR297R + ???
BHMT-01 + 02 + 04 + 08 are all +/- ???
ACHY -01 + 02 +19 are all +/- ???

I am concerned about MTHFR and MTRR as it seems they are specific to Neuropathies. I am currently taking these supplements for a year now as that is what I researched may help nerves In general. I don’t take folic acid at all.

I know being on a PPI can reduce absorption of vitamins and minerals. I do get my Vitamin D and B levels checked every 3 months and they are good. The information above is very conflicting as its saying I need to take methly-B12 and 5-methyl folate but having a COM V158++ is bad to have too much Methyl.



Important links to explain The Methylation Pathway


http://www.heartfixer.com/AMRI-Nutrigenomics.htm
http://www.snpedia.com/index.php/Yasko_Methylation
http://www.youtube.com/watch?v=QRHif...eature=related
http://www.knowyourgenetics.com/The%...20Pathway.html

COMT (Catechol-O-Methyltransferase) – helps to methylate dopamine, serotonin, norepinephrine. Essentially slows down or regulates production of these neurochemicals.

• COMT V158M (-/-) = no mutation – indicates that the enzyme works too efficiently and will use up resources of methyl groups (CH3), ie. available chemical currency.

• COMT V158M (+/-) = heterozygous. Partial defect in system = partial ability to use up CH3 groups. Will be able to handle some methylating supplements, ie. Methyl-12, SAMe, Theanine, DMG.

• COMT V158M (+/+) = homozygous mutation. Both genes are affected.
Significant defect in system. This indicates that the enzyme works sluggishly. Essentially slows down methylation of above listed brain chemicals. In some situations is a better scenario for an autistic child because they will tend not to use up excess methyl groups (chemical currency). Will need to be careful with too many methylating supplements, ie, Methyl-B12, SAMe, Theanine, DMG/TMG. The overuse of these supplements could cause over stimulating leading to hyperactivity, irritability, erratic behavior, etc.


MTRR (Methionine Synthase Reductase – MSR) – is necessary to
regenerate Methyl-B12 so a constant supply of homocysteine can be converted to methionine. Defect = DECREASED enzyme activity which is not ideal.

• MTRR A66G (-/-) = no mutation.

• MTRR A66G (+/-) = heterozygous mutation. Partial defect in system – will need to be cautious with too many methylating substances. – Alec shows homozygous (both genes affected) mutation in this enzyme complex. This translates into decreased ability to regenerate Methyl-B12.

• MTRR A66G (+/+) = homozygous mutation. Both genes are affected. This mutation DECREASES function of enzyme. Definitely need Methyl-B12 – even if COMT ++ (which usually indicates a possible intolerance to methylating


MTHFr C667T (Methylene Tetrahydrofolate Reductase) – helps to convert homocysteine to methionine in the methylation pathway. This enzyme pathway has global effects for immune function, muscle metabolism, neurochemical production and regulation, and detoxification.

• MTHFr C667T (-/-) = no mutation – enzyme works efficiently to convert homocysteine to methionine.

• MTHFR C677T (+/-) = heterozygous mutation. Partial defect in system, ie. one gene is affected.

• MTHFr C677T (+/+) = homozygous mutation. Both genes affected. The enzyme systems works very sluggishly which significantly impairs the process of methylation.

MTHFr A1298C (Methylene Tetrahydrofolate Reductase) – helps to convert BH2 to BH4 for serotonin and dopamine production. Also, has an assistance effect on ammonia detoxification, and protects against too much histamine (stimulates allergic reactions, over- production of stomach acid).

• MTHFr A1298C (-/-) = no mutation – enzymes works efficiently to help with the balance of dopamine and serotonin production, as well as its related ammonia detoxification and histamine lower effects.

• MTHFr A1298C (+ -) = heterozygous mutation. Partial defect system. This translates into a partial problem with A1298C’s function – particularly important when considering the balance of dopamine and serotonin which can increase the propensity for mood swings and non-yeast, non-clostridia (intestinal bacteria) stimming behavior from too much ammonia.

• MTHFr A1298C (+/+) = homozygous mutation. Both genes affected. The enzymes system works very sluggishly which significantly impairs the conversion of BH2 to BH4 and it related effects.


I was reading too much of regular B12 or folic acid can acutally be toxic for someone who has these homozygous, heterozygous mutations. So it might be worth while to take this test before starting on B12 or B9 supplements.

I think you will need a specialist to evaluate these results.

Folic acid is in American food as an enrichment product... in fact quite a bit. But it is NOT the methylated form Methylfolate.
If you cannot methylate it? With the error? That creates a
problem.

If you take 1000mcg of methylB12...you only absorb about 10mcg of it. That is only about twice as much as from food.
I'll have to look this over. But I think a specialist is needed
and you should consult one who understands methylation chemistry.

I also think..given the recent revelations about compounding pharmacies and epidural drugs made there....you should find out what drugs were used on the cervical epidurals you had.
It is possible there is a connection there. Protein in the CSF?
I'd really check this out if I were you. I personally believe this problem with "cheap" substitutes for brand name SoluMedrol,
were being made for many years, and could also be contaminated. The media has not yet released this risk, but I do think it exists, since the company was warned in the early 2000's about cleanliness etc.

Did you ever have a homocysteine test? was it elevated or normal?
I see your MTHFR is +/- which is a mixed mutation. This is not as serious as a +/+... full mutation. People with +/+ mutation here cannot methylate B12 or folic acid properly. Partial mutation means only some methylation. Methylation means moving a -CH3 group from SAMe to the desired location to activate it. People with MTHFR mutations cannot use B12 or folic acid properly.(and would need the methylcobalamin and methylfolate instead of other forms for these vitamins.)

I think at this point you should only pay attention to +/+ presence of mutation (shown in red)

The neurotransmitters in the the brain are methylated and activated by -CH3 group via enzymes. With the mutation showing +/+...you have a decreased capacity for it.

Some of the comments refer to the autistic community because many of them have methylation problems. Often methylB12 is used as a high dose injection for them.

To read more about psychiatric and autistic methylation issues,
consult Pfeiffer Institute online.

Here is some information on COMT:

http://en.wikipedia.org/wiki/Catecho...yl_transferase
wiki

http://rheumatology.oxfordjournals.o.../47/5/572.full

COMT has more information about it, concerning psychiatric conditions, behavior and emotionality. But there are a few references to pain threshold changes in people with mutations in this enzyme. The second link discusses that near the end.
It appears from what I can see, that some studies could not replicate what others found, so at this time, the pain connection is not fully explained.

Your comment about "toxicity" is really a bit strong. Intolerance would be better. Methylation has a link to autism and psychiatric conditions. The Pfeiffer Institute has postulated this.
http://www.alternativementalhealth.c...s/pfeiffer.htm
Errors in methylation according to Dr. Walsh, can result in behavioral imbalances.

This link discusses the MTHFR mutations in detail:
http://findingtherootcause.blogspot..../02/mthfr.html
on that link is this link with a MTHFR diagram/map that is very
interesting:
http://www.mindmeister.com/12694596/...ealth-problems
There is an error on that map showing methylB12 not absorbed orally, and that is not true we know today. I don't know for sure about the other entries however. So I can't vouch for it all, but it remains an interesting graphic.

The word methylation is a general term and applies to many types of chemical reactions in the body. Disruptions in methylation are thought to be involved in bipolar disorder, cancer, etc. The methylation of B12 to methylcobalamin and folic acid to methylfolate is only one small aspect of methylation in general.
http://en.wikipedia.org/wiki/Methylation
It is a fairly large complex biochemical process, that is just being elucidated.

For your purposes of the tests, methylation is explained in your results in specific ways.

In regards to injections you had in your cervical area in the past:
One reason this was not explored in the current emergency involving
the meningitis outbreak, is that the vials cannot be tested from the past, to see if they were contaminated or not --they are gone. The batch that caused this recent outbreak of fungal infection in tissues (mostly the CNS) but there were some joint infections also...had an expiration of 3mos on the label. And it was only a fluke that one doctor examined a patient and found this fungus. In the past, it could have been there a long time and never discovered. I personally believe that people who received this product anytime in the past 10yrs or so could have a festering fungal infection somewhere in a joint or spine (CNS).
Most of the people who died were elderly. With time I think the age of the patient, and other factors may be brought to light about this terrible event. Doctors don't look for fungus infections in people with intact immune systems. People with AIDs are the most likely to have them or those receiving strong chemotherapy for cancer.
The injection of contaminated drugs by doctors, therefore, becomes a iatrogenic issue and sounds like a huge nightmare to me!

Thanks for you research on this. The injections were an attempt to help the burning. This started well before that. So, the injection theory, at least in my case doesn’t fit.

The burning started around same time I started taking Amitriptyline. Works on Serotonin and norepinephrine. Also when I took Lexapro and some other SSRI's that’s around same time burning moved to my back and left chest. Also my burning was worse when I then went on Effexor and then Cymbalta. few months after that.Wonder if that has any link to COM++ .

COMT (Catechol-O-Methyltransferase) – helps to methylate dopamine, serotonin, and norepinephrine. Essentially slows down or regulates production of these neurochemicals.

But I am not on any SSRI, TCA, or SSRI for 3 months. Also 5 months after burning started I did have a Botox injection in my UES. Not sure if the Botox in conjunction with what was going on in my body (reaction to TCA + PPI + not absorbing B12/B9) could of be a perfect storm of things going on in my body?


Just a theory.

Basically COMT is a system to reduce or eliminate (metabolize away) neurotransmitters. (removes methyl groups from them to inactivate them).

MTHFR is a methylating system which will MAKE the same neurotransmitters, by adding a methyl group to the substrates.
So these two systems work to balance things out in the long run.

I really haven't had time to find the other variants of the MTHFR's listed.

This stuff is really new and complex and how it shakes out in vivo may be very subtle. Your mixed mutation in the major MTHFR variant means you will have to use methylfolate instead of folic acid, and avoid folic acid if possible, (because it is in alot of foods in the US), because it competes for folate for transport into the brain, it is thought.

I was hoping you'd get the Cytochrome P-450 test DNA evaluation too, to see how you metabolize the drugs you take.

So you tapered off the Cymbalta? I didn't know you did that.

I still believe you have some kind of iatrogenic (doctor caused) problem. You didn't have this before, and only acquired it after quite of bit of invasive procedures.

Some of the COMT information revolves around too much dopamine (since with the mutation the body can't get rid of excess)...and that is something to look into when you have time. Too much dopamine is connected to addictive behaviors, and some forms of mental illness.

Have you been tested for heavy metals load? The MTHFR mutation appears to be very significant for heavy metal toxicity to build up in the body because they can't be methylated and excreted. That one link I gave stressed that possibility.

Also the dietary suggestions for lots of veggies as sources of natural folate, seems important. Methylfolate is now again available OTC. Solgar makes it, and you might start with it to see what happens... 800mcg a day.

I would avoid however, SAMe, as this is a methyl donor and you can't remove methyl groups adequately.

The Cytochrome P-450 Test is not available yet at http://geneticgenie.org. Would the insurance companies pay for it? If so I can ask my PM doctor to order it.
I did get some good info from 23andme.com that lets me know about possible drug interactions. I don’t think it’s as extensive as theCytochrome P-450 Test.

Right now I’m on Lyrica 500mg daily and started Nuedext 5 days ago.
I was tested for metals via blood test and urine. Not sure if there is a special test I need to take in addition?

I do eat a lot of veggies every day and avoid processed junk.

I think I may try this combo based on a response I received from the CFS forum.

http://www.holisticheal.com/hydroxy-b12-mega-drops.html
http://www.luckyvitamin.com/p-7405-m...odqisAgA&#tabs
*edit*

In regards to your methylcobalamin:
Only about 10mcg is absorbed on a good day from this at the 1000mcg daily dose.
That is not enough methyl stimulation to do much damage, as it has to be diluted in the whole body.

Injections however, release far more methylcobalamin and in some cases doctors give them daily or weekly depending. That could become a methyl load quickly. This is common in the autistic community, for example.

Since you have a mixed MTHFR mutation you cannot methylate well yourself. So if you use hydroxocobalamin, it may not get activated as much as you need it to be. So I would consider that.

I think your first attempt should be to avoid food sourced folic acid and to start Metafolin at 800mcg a day, and watch your reactions. You can increase slowly with time if need be. But very high dosing of methylfolate can be very stimulating and disturbing to some people. Best to start small, and see what happens.

In regards to your links to the vits....
They are very expensive. Solgar's Metafolin 800mcg is
http://www.iherb.com/Solgar-Folate-A...-Tablets/13961
A third the cost. Solgar is a well known reliable company.

Hydroxocobalamin tends to be pricey. You may not find much of a variance with it therefore from company to company.

Here is a monograph on your MTGG mutation:

http://www.ncbi.nlm.nih.gov/pubmed/11472746

It appears to be a factor in elevating homocysteine levels.

I'm just going to post my Methylation SNP status here as well. I'm still working on understanding the results, but it's nice to have someone else's results to compare them to.