After being in and out of the doctors for years with extreme fatigue, at end of September they finally found out it was b12 deficiency (my level was 87). I had more blood tests done to see what was causing it but they all came back clear. Is this normal that you can be deficient for no reason?

Anyway I had my 2 week course of injections (at first I felt a lot better) and now on one monthly but Back to square one. I'm sleeping for 9 hours a night and having at least an hour nap! Should I be feeling better by now?

I've got an appt with doctor after my injection this week as it's also made me flare up with extremely bad acne.

Any help/advice appreciated!

12 Replies

  • I had more blood tests done to see what was causing it but they all came back clear. Is this normal that you can be deficient for no reason?

    Probably a test for antibodies to Intrinsic Factor (a protein needed to carry B12 from the gut to the blood - and one missing in people with PA). It's a notoriously inaccurate test. If positive you almost certainly have PA. If negative.... well, 50% of people with PA give a negative result, so it's fairly meaningless.

    If you do test negative then it's a matter or ruling out other possible causes (do you take certain drugs - PPIs, metformin; are you vegan; do you abuse nitrous oxide; have you had surgery to you stomach or small intestine) to just leave 'absorption problem - probably antibody negative PA' as the only thing left.

    But the cause doesn't really matter. If it's not something temporary then you need jabs for life.

    Ask the doc to increase the frequency of jabs. Explain how much better you felt after the loading doses and how you felt worse again after.

    The acne is a fairly common side-effect. You'll be pleased to hear that it normally disappears after a while as your skin bacteria get used to the new abundance of B12.

  • The blood test was for pernicious anemia and coeliac disease. Just didn't know if there had to be an underlying cause. But with regards your suggestions for other causes it wouldn't be any of those and not a vegan.

    But will suggest to doctor to increase jabs.

    Thanks for your reply :)

  • Logic would dictate that an effect must have a cause. However, there are multiple possible causes and not all of them are things your doctor can easily test for. For example, some people have a genetic mutation that makes absorbing and utilizing B12 more difficult. There are at least 10 genes known to affect how B12 is absorbed and used in the body. Only one of those genes (MTHFR) is well known enough to get an interpretation on at this point in time - and that genetic testing and interpretation would not be done by your GP. You would have to have it done privately.

    In addition to the tests your doctor can't order, there is also the fallibility of the tests that can be done. As fbirder pointed out, sometimes the test results are unreliable. This is notoriously true of antibody testing.

    I haven't had genetic testing done, but I have had a raft of other tests done trying to find the cause of my B12 deficiency and, like you, it all came back 'normal'. I eventually gave up trying to figure out the cause and just focused on getting the right treatment for me. I kept bumping heads with doctors who were insistent that my symptoms, which returned before the next injection was due, were all a figment of my imagination. They were stuck on the idea of what *should* work rather than what actually *does* work.

    You may have to choose which battle is more important to you to fight. It can be very helpful to have a definitive diagnosis, but even with one, there is a strong possibility that getting correct treatment will still be a battle.

    I don't know about you, but I tire easily. I chose to fight for treatment rather than a diagnosis. I think I made the right choice. :)

  • Actually, MTHFR has nothing at all to do with absorption of B12 (I wish I could find the source of this misinformation).

    MTHFR is an enzyme that is responsible for the final step in the folate cycle - producing methyltetrahydrofolate (aka methylfolate). Methylfolate, with B12, take part in a reaction that converts homocysteine into the amino acid methionine. The MTHFR gene codes for this enzyme.

    There are numerous known mutations of the MTHFR gene, only one of which has been researched enough to find any deleterious results of the mutation C677>T. This reduces the stability of the enzyme produced by the gene. If you have just one copy of the gene (heterozygous) the the activity of the enzyme is reduced to about 80% of normal. The body can easily get around this by various means (producing more enzyme being the most obvious). People with two copies (homozygous) have their enzyme activity reduced to about 30% of normal. For many this is still enough, for others they may find some benefit to supplementing with methylfolate rather than folic acid. 400ug a day should be more than enough.

  • Ok, but my point is that there are 10 or 11 different genes known to exist apart from the MTHFR gene that affect B12 and that only that *one* gene can currently be interpreted. The others are not well enough known to be interpreted by the companies that currently offer that service (which makes genetic testing a bit pointless for anyone who happens to have a mutation on any of those other genes). Until there is better understanding and interpretation of the rest of the genes involved, I'm not personally convinced that genetic testing is worth the time or expense.

    Problems with any of the genes involved in the methylation cycle could have the end result of B12 deficiency symptoms. So it is possible to have a B12 deficiency of unknown cause. When new doctors ask me about my B12 injections I usually say it is for idiopathic B12 deficiency. That way I don't have to argue with them over whether it is actually PA or not. ;)

  • I think you'll find that all of the genes involved in the folate cycle have been 'interpreted'. Indeed, they have probably all been sequenced.

    As have all of the genes involved in B12 transportation transformation. I know at least one of them -TCN2 - even has SNPs looked at by 23andMe. I know that because I have one of the mutations.

    Yes, it is likely that the variation in how people respond to different types of B12 can be explained by, as yet, unknown mutations in these known genes. And the best way to discover these mutations is for people to be tested.

    23andMe look at over half a million SNPs, almost all of which are on known genes. But the effects of these SNPs on the activity of the enzyme produced by the genes are, in most cases, totally unknown. But, as more people get tested and supply their health information, the more likely it is that these effects will start to appear in the data. That will give researchers pointers to what they should be looking for.

    But, apart from that and genealogical reasons, you're right - there isn't a huge point in getting tested. There's only one set of gene mutations that would inspire me to do something. Those are the genes for some forms of breast cancer. There really is good evidence that these can have serious influences on one's life.

  • Spots are a common side-effect - it may be that the immune system is kicking back in and over-reacting to things and it may settle down, though the other possibility is that it will be a regular thing and is actually a reaction of the bacteria on your skin to higher levels of B12 - some produce toxins which produce acne.

    Suggest that you monitor and speak to your doctor about possible treatments if it is too bad to bear or doesn't seem to disappear.

  • Hi Emma1703 it is not uncommon for some symptoms to seem to get worse before they get better once the B12 starts repairing damage done to the nervous system by the deficiency.

    It would be a good idea to list all your symptoms, score their severity or improvement on a scale of 1 to 10 each day and present this to your doctor when you ask for an increased frequency of injection.

    Do you know what your folate level is as this is essential to process the B12?

    It would be good to try and work out what has caused the deficiency in the first place and you have answered negatively to fbirder's suggestions (highlighted) but here are few more.

    Vegetarians, vegans and people eating macrobiotic diets.

    People aged sixty and over

    People who’ve undergone any gastric and/or intestinal surgery, including bariatric surgery for weight loss purposes (Gastric bypass).

    People who regularly use proton-pump- inhibitors. H2 blockers, antacids, Metformin, and related diabetes drugs, or other medications that can interfere with B12 absorption including certain contraceptive pills.

    People who undergo surgeries or dental procedures involving nitrous oxide, or who use the drug recreationally.

    People with a history of eating disorders (anorexia or bulimia).

    People with a history of alcoholism.

    People with a family history of pernicious anaemia.

    People diagnosed with anaemia (including iron deficiency anaemia, sickle cell anaemia and thalassaemia).

    People with Crohn’s disease, irritable bowel syndrome, gluten enteropathy (celiac disease), or any other disease that cause malabsorption of nutrients.

    People with autoimmune disorders (especially thyroid disorders such as Hashimoto’s thyroiditis and Grave’s disease) Type 1 diabetes, vitiligo, lupus, Addison’s disease, ulcerative colitis, infertility, acquired agammaglobulinemia, or a family history of these disorders.

    Women with a history of infertility or multiple miscarriages.

    Re the acne - I presume you are having hydroxocobalamin B12 injected.

    I suffered bad side effects when I was "put on hydroxo when it was introduced in the 1980s probably due to one or other of the "excipients" (or ingredients) so have carried on with cyanocobalamin with which I was started 45 years ago.

    I wish you well and hope you have success with your doctor

  • Hi Clivelive

    When you mention thalassemia, do you mean minor or major? I am a carrier and currently trying to establish why mine fell. I was not looking at this as a possible reason. Many in my family are carriers. None of them had b12 problems. I wonder what is the source of this information. I am going to see my haematologist soon because of this tricky combination anyway but seems unlikely that this would be accepted as a reason for low b12.

    Your comments appreciated.

  • Hi activelazy (love the name) I'm not a medically trained or qualified person so cannot answer your question about thalassaemia but wonder if you know of this group


  • Thank you. And I even spelt yours incorrectly. Sorry. Yeah I came across this site recently because I was thinking that thalassemia (microcytic) cam mask b12 (macrocytic). The link you have sent definitely corroborates my thought. I will discuss with haematologist hopefully this month and come back.

    I think it's either b12 or iron or both that are troubling me. Thalassemia gene can not be changed. I wish I could have gene editing (ha ha). They don't even talk about better blood tests😂.

    Whilst I am working hard for what is wrong, at the same time I have to keep my fight on to make sure they don't blame it on anxiety. Because I know that's not the case. It's very difficult to convince the doctors.

    Thank you


  • if you have low stomach acid, then you don't absorb the vitamins in food and some people take apple cidar braggs vinegar b4 meals to help....more common as you age.....the reason for my low b12

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