23andme worth it, if 677 and 1298 tested as normal/normal? (Long-time fibro sufferer)

[UsableThought]

I've had fibromyalgia for 20 years (I'm 55) and all the fatigue, sleep, muscle aches, fuzziness, etc. that come with it. I've also had peripheral neuropathy in my feet for 5 years, of unexplained origin.

Last month I started wondering about B12, so I got my doc to do bloodwork for serum B12, MMA, and homocysteine. The tests came back with high normal serum B12, but also with homocysteine out of range on the high side (14.9). This led me to read up on the subjection of MTHFR and methylation. I have started taking methyl-B12 (5,000 mcg daily) and also methylfolate (I'm now up to 8 tablets daily of the Solgar brand). It's been several weeks now but I have not seen any improvements in my symptoms.

Lastly, I also got my GP to do the blood test for the two most common MTHFR mutations, which I gather from reading are for 677 and 1298. This test just came back today as "normal/normal."

So, here's my question: Given that I have had no obvious response to either the methylfolate or methyl-B12, and that I am "normal/normal" for the two most common MTHFR mutations, should I give up investigating the possibility of genetic SNPs in relation to my fibro and fatigue symptoms? Or would it be worth it to order the 23andme test, since reportedly there are quite a few other potential gene variations besides 677 and 1298?

Any advice appreciated - this subject is very new to me. I was really hoping the MTHFR would come back positive so that I had a possible lead on treatment, but on the other hand I don't want to get on a wild goose chase.

- Randy

 

[ktred]

Hi Randy,

I am anxiously waiting for my 23and me test results to come back, and I'm hoping the results will help me piece together a workable solution for my chronic illness. If the 23and me test is still $99 and that amount is something that won't strain your pocket book, it might be helpful to know what your genetic polymorphisms are.

Do you know what your thyroid situation is, more specifically, what your free T3 levels are? Many people with fibro have lower than optimal free T3 levels. The key word here is optimal levels, not what the labs consider "normal". Improving my free T3 levels and bringing down my reverse T3 has for the most part gotten rid of my painful fibro knots. For many of us here, that would be only part of the puzzle.

I have heard that B-12 test results can be skewed if you are currently taking B-12. In other words, it may not reflect actual cellular B-12 blood levels just how much of the supplement is floating around in your blood stream.

 

[UsableThought]

Do you know what your thyroid situation is, more specifically, what your free T3 levels are? Many people with fibro have lower than optimal free T3 levels. The key word here is optimal levels, not what the labs consider "normal".

Alas, my thyroid levels have never been a problem. I actually did take T3 years ago and it didn't help me. Most of my bloodwork comes back as if I should be in good health . . . quite a contradiction to my actual state of health.

 

[ktred]

Do you what your thyroid test results were? Even if a doctor you like and respect tells you they are normal, ask to have a copy of the results. For many years, I went undiagnosed because I was told my levels were normal. Often doctors will only test your TSH, which is actually a very poor indicator of thyroid status. Also, T3 alone doesn't do the trick for everyone that might need their thyroid status tweaked. I probably seem crazy about this: everyone should get copies of their thyroid tests and never trust what doctors consider healthy and normal thyroid levels. Exceptions would be alternative medicine doctors and oddly, anti aging doctors.

For many of us with CFS, the thyroid angle is only just one piece of the puzzle. I'll let you know what I think of my 23and me test results. I am really excited about getting them back! I was hoping I would get them back today, but I'll just have to be patient.

Too bad the folate and methyl-B12 didn't help you in any noticeable way. I take both of them too, and it's been hard for me to isolate whether or not they have helped.

kat

 

[kday]

There is more than just MTHFR that can cause your set of symptoms. Considering you have peripheral neuropathy of unknown origin out of range B12, and out of range homocysteine, this could point to a mutation such as MTR. MTR is considered the cause of methylcobalamin deficiency, which could lead to the symptoms you describe - peripheral neuropathy and high homocysteine. And if you have the mutation there are other things to assist the conversion of homocysteine to methionine - such as TMG or DMG.

Serum B12 test isn't such a good test. MMA is a better indicator of B12 status, but it's my personal opinion that it's important to not rely on the results of these tests.

You have less than a 1% chance of having a homozygous MTR mutation and treating it can require extremely high doses of methylcobalamin especially in combination with MTRR mutations. Some physicians have found that patients have benefited from taking up to 50 mg of B12 a day with these mutations (an insane amount, I know).

I am actually homozygous for MTR, and I have seen several others that are homozygous for MTR in a small sample, so I am convinced that this mutation may be much greater than 1% in the CFS population. However, I don't have a large enough data pool to draw conclusions. I plan on looking at a larger data pool in the near future with permission from users of my website to see if I am right.

http://ghr.nlm.nih.gov/gene/MTR
http://en.wikipedia.org/wiki/5-Methyltetrahydrofolate-homocysteine_methyltransferase

Nevertheless, if you get a 23andMe test done, it will show you other health risks and carrier status for certain diseases.

For an example, I am a carrier of Tay Sachs Disease (good to know if I choose to have children), and I have something called pseudocholinesterase deficiency which leaves me unable to tolerate certain anesthetics (they could potentially kill me) in surgical situations or dentistry. It also causes sensitivity to certain pesticides, so I am now making sure to eat almost all organic.

All of this info was found out right on 23andMe's website.

So my point is, if you don't get anything from your genes involved in methylation, you might get some other important health data. And in the case that you don't, there are ancestry features that you can use to connect with people who are your cousins/relatives.

 

[Helen]

Hi Randy,
I was told by an experienced B12 doctor that it might take up to 3 years of treatment with B12 before symptoms of polyneuropathy disappear - if they ever do. The nerves might have become too damaged. No labtest for B12 is 100 % reliable according to him.
I agree with kday that another genetest could be of great value. At least it was for me. All of my symptoms were explained by the Comprehensive Methylation Panel from www.holisticheal.com and from Genovations DetoxiGenomics profile http://www.gdx.net/product/10038. Thanks to kday most of the genes included in these two tests will be analysed from 23andme results in the http://geneticgenie.org.
Polymorphisms in the GST genes included in the DetoxiGenomics test have been found to contribute to polyneuropathy. Mercury from amalgam fillings has been proposed to be a toxic substance that couldn´t be metabolised properly with GST polymorphisms. Mercury might also impair methylation. Impaired methylation seems to be a necessary (but not sufficient) factor for ME.
Helen

From PubMed:
Brain Behav. 2011 Nov;1(2):135-41. doi: 10.1002/brb3.26.
Polymorphisms of GSTT1, GSTM1, and EPHX genotypes in patients with cryptogenic polyneuropathy: a case-control study.

Lindh J, Söderkvist P, Fredrikson M, Hosseininia S, Tondel M, Persson B, Vrethem M.
Abstract

The aim of this study was to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1), Glutathione S-Transferase Theta-1 (GSTT1), and a low-activity genetic variation of epoxide hydrolase exon three (EPHX*3) affect the risk of developingpolyneuropathy. The enzymes of these genes are important in the metabolism of toxic compounds. Seventy-nine patients with cryptogenicpolyneuropathy (equivalent to chronic idiopathic axonal neuropathy) and 398 controls were tested for the genetic polymorphism. Medical records were reviewed to collect data regarding clinical findings at diagnosis, and exposure data was collected via questionnaires. The odds ratios (ORs) for the null forms of GSTM1 and GSTT1 and the normal activity YY form of EPHX*3 were close to one except GSTT1, which reached 1.86. The highest risk ofpolyneuropathy was found in smokers with GSTT1 null, who had a 3.7 times increased risk. Interactions between genes were analyzed and confirmed the increased OR for GSTT1, which was strongest if the patients had the low-activity HH form of EPHX*3 (OR 2.37). Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances that could lead to nerve damage in the peripheral nervous system.
PMID:

22399093

[PubMed]
PMCID:

PMC3236538

Free PMC Article

 

[Helen]

Kday, could this be of some help?

https://docs.google.com/spreadsheet/ccc?key=0Ar76dNWyEQLIdExKZUhfXzFUWHpkWnZObk1TM1dxX0E&hl=en#gid=0

I think it was linked in a message in PR.