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B12 Deficiency, MTHFR, MTRR, MTR and TCN Gene Mutations

Hi - I'm new to the site however I'm trying to learn fast :) I will try and keep this as brief as possible.

My Grandfather and Father had Pernicious Anaemia and my father received B12 shots for 25 years before he passed away. I'm a 45 year old male and over the last 2 years I have been showing signs of potential PA (or B12 deficiency ?). I won't bore you with all my symptoms as it could also take a while.

So far, the Doctors have not agreed that my symptoms are related to B12 deficiency as my B12 levels in the blood are "normal" at 400. I have tested negative for Intrinsic Factor and Homocysteine & Methyl malonic Acid levels are also fine. All other blood tests are ok but I have tested POSITIVE for Parietal Cell Antibodies. However despite this, symptoms and family history my Doctors are refusing to treat me for suspected B12 deficiency. I 'm aware that B12 in the blood is almost irrelevant as it's what's in the cells that's important however this seems to be ignored by my Doctors. I have also presented a copy of the British Journal of Haematology to my Doctor however he is refusing to follow these guidelines. To take the edge of my symptoms I have been taking Methyl cobalamin sublingual and Methyl Folate daily.

Anyway, the reason for my post is that I now have my 23andme results and I have run the raw data through genetic genie which show mutations at critical areas in the Methylation process. These are...

MTHFR C677T RS1801133 AG (+/-)
MTHFR A1298C RS1801131 GT (+/-)

I believe that makes me compound Heterozygous and I also have mutations on the following required for effective methylation.

MTR A2756G RS1805087 AG (+/-)
MTRR A66G RS1801394 AG (+/-)
MTRR A664A RS1802059 AG (+/-)
BHMT-02 RS567754 CT (+/-)
BHMT-08 RS651852 TT (+/+)

My TCN1 and TCN2 results are as follows, however I'm not sure if these are "mutations" as they are out with the report given by Genetic Genie.

RS16988828 AG, RS9621047 AG, RS9606756 AA, RS740234 AA, i5004509 TT, RS1801198 CG, RS5749135 CT, RS2283873 GG, RS9621049 CG, RS4820886 TT, RS2301955 CT, RS10418 CT

RS117699377 CC, i6042918 II, RS557564 CC, RS141411985 GG, RS61903593 AG, RS526934 AG, i6042919

Obviously a lot of information to take in but I guess the questions I have are....

1/ Do these Mutations point to a problem in my Methylation process and what does this mean for me ?
2/ If so, how do I prove this to my Doctor - Are there any medical Journals / reports that I can present to him to explain this and that I'm not mad ?
3/ Are there any mutations / issues with my TCN1 and TCN2 results and if so how do I prove this ?
4/ Are there any Doctors (preferably in the UK) that could help me prepare a report to my GP with my Genetic results ?
5/ Any other "basic" information / videos to help a "newbie" get up to speed on the BASICS would be appreciated.

Thanks in advance of any help provided and apologies if any of my questions / points are deemed to be basic.

I believe that makes me compound Heterozygous and I also have mutations on the following required for effective methylation.
You can't use 23andMe data to determine if you are compound heterozygous. To be compound heterozygous, you must get one bad allele from each parent. But 23andMe simply reports alleles in alphabetical order, so you can't tell if the problem alleles are on different strands.
1/ Do these Mutations point to a problem in my Methylation process and what does this mean for me ?
You might be a bit slow in producing methylfolate (30% or 65% of ideal, normal is 70% of ideal), but that should be completely compensated for with a normal dose of folate from supplements or eating vegetables.

Has your homocysteine ever been tested? It should be a very mainstream thing to get tested (it's often done in annual preventative physicals in the US), and should be a good reflection of whether or not your B12 levels are actually sufficient.


Senior Member
South East England, UK
I have heard many times that a blood level of 400 for B12 is far too low, it should probably be double that. Admittedly this is from integrative physicians but that is their experience of treating people using natural methods. Probably a trial of either hydroxycobalamin or methylcobalamin would be a good idea.

You probably already know that some of us don't do well with too many methyl groups so it might be a good idea to start off with tydroxycobalamin. I also benefit from adenosylcobalamin which seems to help with energy in the muscles.



Senior Member
Hi Ajay,

What about your lab results for iron, e.g. ferritin? Low iron may be a sign of B12 deficiency as B12 is needed to keep the iron staying. Did you get testet for MCV (another test for B12 that reflects the form of the red blood cell)?

Your mutations might make you more vulnarable to methylation issues as they may affect both your folate metabolism and your B12 metabolism. You need extra methylfolate compared to a person without the MTHFR mutations but I doubt that you would find a doctor, except for someone that has researched this, to propose substitution. Methylfolate is the form of folate that you need. If you get it from food or from supplements doesn´t matter. Your genetic capacity to produce the enzyme (MTHFR) is about half of normal so it surely is something to bother about to get enough of methylfolate daily.

If your capacity to produce B12 in your gut due to PA is decreased, and on top of this some mutations, this could make things worse. I agree with bertiedog that 400 of B12 in serum could be low. I learnt from doctors/B12 experts that testing with all available tests, as well as noting symptoms) before a trial with B12 supplementation is the best way to confirm a possible deficiency.

A panel of methylation factors can be made from ELN lab, an European sister company to
http://www.hdri-usa.com/tests/methylation/ . Genetics isn´t necessarily reality, so better to know what´s going on if possible

I hope you can find a specialist to work with. Just some thoughts....


Senior Member
Homocysteine & Methyl malonic Acid levels are also fine
Please note that the lab range for Hcy is too wide, and you want it between 6 and 8.

I agree that serum B12 at 400 might be a bit low, I try to always keep mine above 500 and to eat plenty of methy donors (butter, eggs, olive oil, and I use lard or butter to cook) to activate the B12 and the folate from vegetables. Avoiding refined oils is crucial to activate your vitamins.
Hi - Thank you all for your feedback. I have downloaded the information on MTHFR that is in @ Caledonia signature and that has been a massive help.

Thanks again and will let you know how it goes.


Senior Member
I was surprised to the post suggesting B12 at 400 low. My level was 119 at first. Iron was low too. Now with the help of B12 injection treatment my levels are just under 300. I was told 500's are good. But never achieved that level. Apparently, intrinsic factor is OK. Whatever that means, I was not told much about it. I feel B12 injections are wearing of quicker nowadays. I feel I could do another injection after a month not 3!
The other thing is I feel I get less swollen or maybe thinner (I honestly don't know which one) after the injection, then got a bit fatter. Is this normal? My appetite and diet is steady. I never had weight issues in my life.