I'm fairly new here and this is my first post. Has anyone had genetic testing for MTHFR polymorphism? I am awaiting genetic test results but based on my family history, my not-yet-managed B vitamin deficiency seems to be due to polymorphism. The defect is very common but affects people differently. My grandmother passed away in her early 30s, reportedly from leukemia. I'm now wondering if she was suffering from anemia linked to the polymorphism. Before my deficiency was discovered, every system in my body it seems began to fail. Knowing the reason doesn't really change treatment, but I'm sure it helps to know why some of us just cannot keep our levels up. It may also get the attention of practitioners who hesitate to treat or continue treating without Intrinsic Factor as the culprit. In the States, the genetic test is less than $100 out of pocket, through a medical professional. I believe the information on MTHFR polymorphism is also provided with commercial DNA tests such as 23 And Me. The MTHFR defects are a newer discovery and they are finding many diseases associated. One thing to note is that methylation is a huge factor. Folic acid and cyanobalamin can be toxic in a person with MTHFR polymorphism. This could explain why some of us react differently to different forms. Thank you to everyone for posting! I enjoy reading through them every evening. Learning a lot.

16 Replies

  • Yes, I have been tested and I am homozygous for the most common, and the only well studied MTHFR mutation - C677>T. Only about 8% of. The population are homozygous, so I wouldn't say it's very common.

    Also, it is nowhere near as terrible as some scaremongering clickbait websites would have you believe. I lived with it for over 50 years without suffering any of scores of nasty ailments attributed to it. It was only when my immune system went rabid last year that it had any noticeable effect.

    The gene is responsible for making the enzyme methylenetetrahydrofolate reductase (also called MTHFR). This enzym is responsible for the formation of methylfolate, which is the agent that is used to methylated B12.

    The mutated enzyme works in just the same way, but it is not as stable, so it doesn't last as long.

    People who are heterozygous for that mutation can still perform that reaction, at about 80% of the normal level. Which would be nearly indistinguishable from the norm.

    People like me who are homozygous can perform the reaction at about 30% of normal.

    But the body has ways to get around these problems. One way is to increase the rate at which it produces the enzyme.

    For most people a single MTHFR mutation will make no difference. For most of the 8% who are homozygous for the mutation it will make no difference. The remaining tiny minority may benefit from taking a supplement - and it's not methylcobalamin.

    Remember that MTHFR makes methylfolate. So the key is to supplement with methylfolate. When I get off this train I'll post a link to my favourite video about the topic.

  • OK. Here's that video -

  • not sure where 'cyanocobalamin can be toxic' to someone with MTHFR comes from. The only condition where it causes problems is leber's syndrome which, as far as I am aware has nothing to do with MTHFR, but to do with sensitivities to the cyanide molecule.

    fbirder do you have any comments.

  • Hi Gambit62,

    Fbirder might be still on the train! eh

    J 😜

  • The video is interesting, thank you for posting. I am a skeptic in general, but always with an open mind. I find it odd that the Dr. in the video seems to feel he is the authority. I wonder why so much research is going on currently if he has all the answers.

    I read things such as this which makes me wonder:

    Yes, this is representative of a small population as it is one specific mutation. So we see that B 12 deficiency occurs in this specific mutation and perhaps further research shows a tendency toward deficiency with other mutations. Regardless, for those with this mutation, an otherwise unexplained B12 deficiency could be due to the mutation.

    I'm curious how fbirder has attributed more recent issues to MTHFR? I'm not asking you to share personal information! I'm just wondering how you and/or your health provider determine any issues are the result of the mutation.

    The cyanobalamin and folic acid can be toxic in that they are not able to be processed efficiently in some people. Its all scientific and difficult for me to fully understand, but what I get is that if your body cannot process or methylate efficiently, there is a build up of toxic byproducts in the body, homocysteine being a big one. A person may be unaware this is happening at all as it can take years for health issues to mount.

    I personally do not know what is behind any of it as I am far from an expert. I can read. I can understand a fair amount of what I read. But knowing what is relevant or how to determine validity of studies and research is beyond me.

  • thanks.

    It isn't the cyanocobalamin or the folic acid that are toxic - it is not having enough of the relevant B9/B12 form available at the cell level to support the processes going on at the cell level that causes the build up of harmful by products rather than reprocessing into the useful building blocks. This doesn't mean that you should avoid cyanocobalamin or folic acid but that you would need more of these forms in order to get the same amount of methylated form at the cell level than someone who doesn't have an MTHFR problem.

    MTHFR affects B9 more than it affects B12 but even so it is not completely stopping conversion but would mean that more of the folic acid would be needed to ensure that the body made enough of the methylated form for it to be used ... same with B12 but at a lower level ... though I do have to admit to having come across a study which showed that high use of folic acid seemed to induce artifical MTHFR problems in mice - however this was at really high levels of supplementation.

    There are some genetic variants involving other processes where some genetic combinations mean that methylated forms of B9/B12 can actually cause problems - just been looking into COMT and trying to understand it a bit (definitely not a biochemist :)) - where one combination interferes with processes in the brain and can cause problems with pain, balance, mood.

    This article from 2014 looks at some of the genetic interactions on B12 processing and neurodevelopment

  • I have the homozygous form of the gene as well, and also couldn't relate to the doom and gloom I've read elsewhere. I got my test from 23andMe, too. I do have a B12 deficiency but possibly that has been caused by taking NSAIDs for the last 5 yrs for back pain? Otherwise I am now developing Hashi's but that might have little to do with MTHFR. I think there's an awful lot still to be discovered.

  • hi,

    I often read of people who have had their MTHFR tested by 23andMe, which is odd because when I emailed them they replied:

    "Thank you for contacting the 23andMe Team. The 23andMe Personal Genome Service does not include a health report on MTHFR."

    Maybe they have stopped this particular service?

  • I'm not sure if I got a health report from them regarding MTHFR. I think not.

    However, there are other companies that can examine the raw data and look at the MTHFR SNP (Single Nucleotide Polymorphism).

    The two I use are Promethease and Genetic Genie. The latter will look at all of the genes for enzymes involved in methylation reactions.

    But you do need to look at the real science behind your results.

    And if you take them to your GP they'll most likely smile knowingly and totally ignore them.

  • Ok, thanks.

    I appear to have b12d without any "reason", since I have a great grandparent who died of PA I thought the genetic route might be worth investigating (even though I do not have PA myself, apparently)

  • Who says you don't have PA? The normal antibody tests are notoriously inaccurate (Martyn Hooper, chair of the PAS tested negative three times).

    If you have a g. grandparent that died of PA then there's a reasonable chance you have it. Do any other members of your family have autoimmune diseases - Type 1 (or 1.5) diabetes, rheumatoid arthritis, lupus, hypothyroidism, scleroderma, etc., etc.? Because they all seem related, so a relative with one would seem to suggest a greater chance for you to have one (or more) of the group.

    Apparently some researchers are looking into the genetics of autoimmune diseases. If they find a (or a few) simple mutations that are responsible then there may be some hope for us in the future (well, maybe for our kids). A new(ish) technique called CRISPR promises the ability to edit the human genome, not just in embryos - but it every cell of the body.

  • Yes, I know, although both my IF and parietal cell tests were exceedingly low (i.e. negative). My daughter has coeliacs (which I "don't") which isn't PA admittedly but as you say a lot of the autoimmune diseases appear to be related, and I do seem to benefit from a gluten free diet.

    Theres also a lot of new research suggesting the human gut micro biome is responsible for auto-immune diseases.

    So I'm not sure whether I should be eating sauerkraut every day or having my genes "edited" !

  • I am new to this but read through the post and wanted to ask if anyone experienced the same symptoms. I was diagnosed October 2015 with the MTHFR heterozygous Gene. Today I was diagnosed with pernicious anemia. I'm a 41 year old female and I don't take heartburn pills or anything except for prescription vitamin D2 50,000 once a week and birth control. I had a miscarriage in September of 2015 and since then I've gained 25 pounds. The doctor kept saying I was depressed etc etc I've been battling going to the doctor's for two years telling them something was wrong finally I got the diagnosis today. I went to my regular doctor two months ago and my vitamin B12 levels were at 77. She prescribe me self-injections 1000 once a week. It was the cyanocolbamin injection. The crazy thing was that the injections made me so sick, like I was weak with the flu for a whole month I felt awful just taking one injection a week so I asked the doctor was this normal and he said no not at all and to quit taking them so instead I take the sublingual vitamin B12. My levels are at 250 now, but I know that that's the low end of normal and I need to get them up; but I wanted to at least mention this as I was reading about when you are missing the MTHFR Gene that the cyano can be harmful. I know that every person is different but I can tell you what I experienced and like I said I felt like I had the flu for a whole month that's how bad my bones ached. After I quit the injections, I felt so much better after 3 days.

  • Hi MChavez127,

    Maybe you should make a new post as a lot of members won't see this unless they have opted to 'follow' the original poster.

    Hope this helps. 😊🍀

  • I was diagnosed October 2015 with the MTHFR heterozygous Gene...

    I was reading about when you are missing the MTHFR Gene that the cyano can be harmful

    About 99% of the population will be heterozygous for one MTHFR SNP (or worse). There's only one condition that has shown reproducible results and that's being homozygous for the C677>T mutation mentioned above and carried by about 8% of the population.

    If you were missing the MTHFR gene then you wouldn't have survived to birth.

    Even if you had that mutation it couldn't possibly make cyanocobalamin harmful.

  • I don't think that harmful is probably the best word. I did have side effects though. I took one shot a week and I was so achy, like I had the flu. Everyone kept telling me oh it's just because it 's the first shot, or it will go away in a day. However, I kept taking the shot, once per week and for the entire month I felt awful. It did increase my levels though. I changed to the 5000 sublingual methyl B12 and I have no symptoms. Maybe it's not due to the MTHFR gene, maybe I just have an allergy to Cyano? I'm not really sure, I'm not a Dr. All I can tell you is what I experienced. In case you are wondering if I was that sore because I was at a level of 77, I would respond with a no. Last year I tested at 79 and I took the sublingual tablets for a month and never felt that way. The problem was that I quite after 3 months once my level went up to "normal" when I retested. I'm only at 250 for my B12 level which is low on the normal end. Now, that I've been diagnosed with PA, I will have to supplement everyday and my goal is to get to the 900's to see if I actually feel different. I'm not really sure how to read all of this but my genetic test states I am heterozygous for the C677T polymorphism in the MTHFR gene.

You may also like...