"The 776C→G polymorphism of the vitamin B-12 transport protein transcobalamin gene (TCN2) (rs1801198; Pro259Arg) is associated with a lower holotranscobalamin concentration in plasma. This effect may reduce the availability of vitamin B-12 to tissues even when vitamin B-12 intake is adequate. Clinical outcomes associated with vitamin B-12 insufficiency could potentially be worsened by high folate intake."
"Odds of neuropathy were 3-fold higher for GG genotypes than for CC genotypes (OR: 3.33; 95% CI: 1.15, 9.64). When folate intake was >2 times the Recommended Dietary Allowance (800 μg), GG genotypes had 6.9-fold higher odds of neuropathy than CC genotypes (OR: 6.9; 95% CI: 1.31, 36.36). There was no difference between the genotypes in the odds of peripheral neuropathy when folate intake was ≤800 μg (OR: 1.5; 95% CI: 0.18, 12.33)."
Translation: if someone has an inefficient B12 transporter gene, then taking a moderate amount of folate every day could block their B12 transport mechanism, and give them neuropathy with normal B12 levels.
The gene variation in the study is very common (rs1801198 on the TCN2 gene), and the amount of folate (800 micrograms) studied is just two times the RDA, so this situation could easily apply to many people.
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I had genetic tests as the consultants were certain I have one of the rare genetic b12 problems but they messed up the tests and because they are so expensive I can't get them to do them again. Diagnosed with PA after the genetic tests on MMA test results alone as they refused to do the PA anti body tests.
They are finding a lot out through science so fingers crossed it will be cheaper and easier to get tests done in the not too distant future. x
I like that this study shows that B12 deficiency symptoms can be induced with only 800 micrograms (0.8 milligrams) of extra B9 (folate).
800 micrograms really isn't very much; a multivitamin plus food could reach that easily. Folate has typically been considered relatively benign. For example, people with resistant depression are sometimes prescribed Deplin, a nutraceutical that contains 7.5 mg or 15.0 mg of folate per dose. Many of us take Metafolin or Quatrefolic to bypass MTHFR mutations; this study shows that we have to careful not to meet but not exceed our body's folate requirements.
it's not just the stated TCN2 polymorphism that's of concern. There may be many other glitches on this gene that impair its function, or errors in the promoter region of this gene, or errors in other genes in the B12 pathway. It might not be feasible to isolate the problem through gene sequencing. It may not really matter what the exact gene problem is, as long as we know that folate has the potential to cause tingling.
So if someone is experiencing neuro symptoms that resemble a B12 deficiency, they might:
1) supplement B12, hopefully by injecting an active form
This is the opposite of what I am following. That is b12 injection every 2nd day and 5mg folic acid daily. On the onset of my neurological symthomps I was not substutiting. Can I then assume that my neurological symthops are not due to too much folic acid?
5 mg a day is a very large dose. Normally that would be given for a short period when somebody has a serious deficiency. There are some people who think that prolong d exposure to high levels of folate might be harmful.
I have been taking 800 micrograms of folic acid daily as well as injecting B12 every other day for a year now. Also vegetarian diet rich in leafy greens, eggs, cheese, Cornflakes, kokomilk, Marmite etc etc etc (doing my best here).
Recently upped my work hours, and, along with some others, these symptoms returned: hair loss, gums bleeding, mouth splitting and bleeding at corners again. These improved when I supplemented folic acid and multivits & minerals - so much so that corners of mouth healed completely, and that was a 10-yr problem for me.
So I'm having blood tests again to check folate and ferritin levels. These were always at very low end of range except after NHS 3-month treatment for both- then high, but dropped quite quickly as soon as course finished. Not tested by GP since I started SI a year ago. Haematologist was the last one to check all my blood levels: ferritin, iron, folate, B12 ..and surprisingly said in her letter that these were all "normal": would have expected B12 at least to be through the roof . Wrote to her but could not get her to expand on her previous summation. In fact got no answer at all. >sigh<
What were your MMA levels like, to get a diagnosis on this alone?
Mine have remained consistently raised - between 350-400 nmol/L (range 0-280) despite SI every other day, and was told by genetics consultant that this was not nearly high enough to determine B12 deficiency .
Genetics consultant looking at my DNA anyway, and will get back to me next year with appointment to discuss results.
Interesting. I am getting no treatment now at all, but was dxed PA in 2012 and went through all the process of loading doses, three monthly, then because I had neuro stuff two monthly, and in 2013 was started on folic acid 5 whatever it is, by 2014 was feeling far fewer neuro syptoms but unexpectedly felt immensely worse, total lack of motivation energy + terrible brain fog etc., and very unwell but not like before.
Around august that year I needed a new prescription and forgot to request it so no folic acid, and suddenly started to regain some energy and clarity of thought so much so that early in 2015 took the trip of my lifetime to revisit a place that had been my home for 15 years. Around that time and during the time of that visit my neuro, very much against the wishes of my GP put me onto high dose b12 for 3 months, every other day shots. I was immensely better but had the last shot late in march.
Anyway your posting really interested me because I test a little above the bottom end of the b12 scale, and my gps have consistently refused to treat me with b12, they are very hardline about it, and refuse other patients too. If your bloods normalise and you have a neg IFA thats it, no PA, and no other cause of b12def considered, and no referrals other than they will consult a haemo over the phone on your behalf (?? ).
But I had responded very well to b12....... and have other genetic factors that can be found with it.
I spent 2016 very ill and hospitalised with something unrelated and last year recovering. I have got socks and gloves neuropathy that is quite severe that is put down to this illness, but while It could theoretically be related it feels more exactly like b12def, which is what I was dxed with originally! So it's crazy not to treat me, (even if it were done to test the hypothesis, and conform to the guidance on treating symptomatically) and costing them and me a lot.
The possibility that I could be in this category you describe is quite high given my sensitivity to folate, and perhaps there are other factors too. I change doctors soon, and live in hope. I read regularly here and this is a first intimation that there maybe answers for me.
If you were diagnosed with Pernicious Anaemia in 2012, you still have it now. The course of B12 injections you had isn't a cure.
Have a look at the Pernicious Anaemia Society website for more information. Also look at list of symptoms. There are many related auto-immune illnesses (Hashimoto's, psoriasis etc) that you might not be aware of. Just saying this because you mentioned being very ill in 2016. Some drugs can affect B12 levels - nitrous oxide for example.
Get your B12 level checked again if you can- it may have dropped since your last test. You might need to keep a record of your daily diet so that new GP can't dismiss any regression as an "extrinsic factor" problem (= your fault ). And keep hoping.
(If I had a PA diagnosis, I would ask GP for a printout and have it framed! )
Thanks Cherylclaire. I know this, but my doctors don't, they have this weird idea that only blood test data can be used to diagnose. I have other autoimmune conditions, including generalised vitilogo so severe that I have 95% depigmentation, and psoriasis that is hindering wound healing, to name two. My response to b12 was enough for the dianosis to be made even though I had a neg IFA, but since then only serum b12 taken which was pretty low two years ago at 288 after 3 months of every other day! But was regarded as within the normal range in spite of ongoing symptoms that have considerable worsened since then. Socks and gloves are more like trousers and long sleeves.... but I am just a troublesome patient who looks at the internet, and what do I know anyway.
Well, I do know for one that they are flauting the guidelines. But they will not be budged so next step is new doctors. which I have not been able to do for practical reasons until now. It is not the only problem I have had with them tbh, they are still treating me as if my blood pressure was the same as four years ago, after several readings this year showing It is dangerously high. District nurses are my friends right now so have advised on best gp option for me.
Thanks for the advice, I know most of this stuff but as for most people it is not what we know that counts when seeking treatment.
I agree with you. You need to be able to trust that your GP is doing her/his best on your behalf- and is not so gullible that they will go along with consultants, despite what they are seeing with their own eyes.
I have had some appalling comments from consultants, including:
"Your cognitive problems are because you used to smoke, and oxygen is now not reaching your brain" (haematologist)
"B12 is highly addictive" (same haematologist)
"B12 is toxic" (a different haematologist)
"I don't know much about B12, but you put a convincing case: tell that to your haematologist next time" (neurologist !)
Luckily my GP is bright, experienced and still trying to help me to get "me" back. Or at least enough of me to be able to work a couple of days a week without problems.
I hope you can find a good GP soon. One that looks and listens.
I have no where near the knowledge others have on the subject of b12 deficiency but I have successfully SI for about 18month
During last 6 months I have taken additional folate having read it’s important for the utilisation of b12 but have gradually felt b12 deficiency symptoms creep back
I’ve thought it was b12 not working and changed to a more reputable supplier but still no good
Have recently expirienced swollen sore tongue and have thought it’s low folate because of the increased frequency of b12 injection so have taken even more folate
Now this is making me wonder if the opposite is the case
I’m so confused and getting even more desperate to get back to the person I was when b12 was definitely working
Only way to know for sure is to get your folate levels in blood checked again. Symptoms, I'm told, can be similar: B12 deficiency/ too much folate. I've always found hair loss and bleeding gums to be good signs that I need more folate. Trouble is, we are all different, -and it could as easily be iron.
I’ve arranged to see my Gp next Tuesday in the hope I can persuade her to do bloods
She’s aware I SI but doesn’t really believe it’s anything more than a placebo because my initial bloods showed b12 in normal range albeit at the very bottom. This is despite having very definite symptoms including Neurological which have been totally addressed up to this point through initial loading doses done by Gp and ongoing SI
Frustratingly I’ve taken folate today is it possible to counteract this by taking more b12
I should point out my sore swollen tongue now looks like oral thrush and gp prescribed nystatin over the phone to treat
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