Vitamin B12 deficiency – time for a rethink?

2 Mar

Traditional view

NHS Choices offers a traditional view of vitamin B12 metabolism and diagnosis and management of vitamin B12 deficiency anaemia.

An up to date review was published recently link

Vitamin B12 deficiency anaemia or folate deficiency anaemia develops when a lack of vitamin B12 or folate causes the body to produce abnormally large red blood cells that cannot function properly.

The main symptoms of vitamin B12 deficiency or folate deficiency anaemia are:

  • tiredness
  • lethargy (lack of energy)

View from special interest group(s)

Conversations with members from Pernicious Anaemia Society and B12 deficiency support group indicate there is more to the cobalamin metabolism story than the traditional view describes.

Recent articles and abstracts scattered through the scientific literature point to a more sinister effect on human biology when there is functional deficiency of B12.

Adenosylcobalamine, the adenosyl form of Vitamin B12, is needed to keep the TCA cycle running smoothly, and many people with B12 deficiency suffer a “dreadful fatigue”. But it’s a complicated process getting B12 into mitochondria, and an awful lot of things can go wrong.

A key to better understanding is awareness of biochemical reactions in which vitamin B12 is a crucial. These include [link]:

  • conversion of odd chain fatty acids (specifically propionate) into succinate
  • conversion of homocysteine into methionine via methyl group donation

Medically Unexplained Symptoms – is this a B12 deficiency syndrome?

This week it was proposed that any patient with medically unexplained symptoms should be referred for CBT. It was estimated this may save the NHS £3 million per year. No mention by the authors of the report to explicitly exclude functional deficiency of vitamin B12 [Advances in Psychiatric Treatment (2009)15: 146-151doi:10.1192/apt.bp.107.004606]

Do not forget magnesium deficiency – it is important to ensure magnesium levels are normal in any patient who is taking high dose proton pump inhibitor especially if also prescribed a diuretic agent.

The neuropsychiatric changes caused by functional B12 deficiency may predate the typical changes seen in the blood by months (perhaps years). These are detailed by MacDonald Holmes [JMD Holmes – British Medical Journal, 1956].

McAlpine (1929) said, ” Mental changes occur not uncommonly in pernicious anaemia. They range from states of depression accompanied by loss of mental energy to definite psychoses…” [McAlpine, D. (1929). Lancet, 2. 643]

When there is doubt about the status of vitamin B12 rather than repeat the test in 6 weeks in “borderline cases” as is the present practice, serum methylmalonic acid levels and serum homocysteine levels should be measured.

Measurement of methylmalonic acid, total homocysteine, or both is useful in making the diagnosis of vitamin B12 deficiency in patients who have not received treatment. The levels of both methylmalonic acid and total homocysteine are markedly elevated in the vast majority (>98%) of patients with clinical B12 deficiency including those who have only neurologic manifestations of deficiency (i.e., no anemia). [Stabler, S NEJM 2013]

Implications for general practice

Clearly there is a need to review how we view vitamin B12 metabolism. Recognition in primary care of functional deficiency of vitamin B12 will require medical curricula to pay better attention to this. Haematology does not have a monopoly on clinical features of vitamin B12. There are too few haematologists and neurologists, at least in the UK to provide clinical opinions when vitamin B12 deficiency is suspected. This leaves it to general practice and family doctors to learn more about the protean manifestations of altered vitamin B12 metabolism.

With performance managed healthcare becoming the norm around the world, it may be time to press for explicit scrutiny of vitamin B12 levels in patients with long term conditions including many in the following systems: gastrointestinal, hepatic, psychiatric, neurological, endocrine, renal, and non-malignant anaemias. Only then might we be certain that a scourge of (modern) society will be beaten.

David Lewis



I would like to thank @b12unme for educating me about this issue. Any errors and omissions are mine.

13 Responses to “Vitamin B12 deficiency – time for a rethink?”

  1. B12d Hugo Minney March 3, 2013 at 20:45 #

    Dr Lewis is spot on – we assume that anything unexplained is “all in the mind” and try to save £3million with CBT, when it may be as simple (and devastating) as a nutritional deficiency. If this were tested, the savings could be potentially £854million per year!

  2. Re:Cognition Health March 4, 2013 at 08:34 #

    An excellent and thought provoking piece. Brain science is rapidly developing and the historical divide between psychiatry (“it’s in the mind”) and neurology (“it’s in the brain”) is increasingly anachronistic. Many symptoms and conditions have multiple components and need multi-disciplinary input to enable GPs and patients to manage conditions effectively. Recent example we have seen include:
    – misdiagnosed Korsakoff’s
    – PTSD masking underlying mild TBI previously undetected
    – Alzheimer’s diagnosed as depression, and depression diagnosed as Alzheimer’s with patients on the wrong medications
    – cognitive function impairment caused by B12, polypharmacy for other physical conditions, and thyroid dysfunction
    – under-detection of lacunar stroke
    You’d be surprised how many patients with cognitive function impairment have a reversible cause.

    • Sue Purcell May 12, 2013 at 18:18 #

      Totally agree, I have hypothyroidism and I had to fight tooth and nail to get a diagnosis, now my bloods keep showing my red blood cells as bigger than normal but I cannot get any doctor to take this seriously!! So damn frustrating!

      • maturinuk May 16, 2013 at 03:14 #

        Sue, thank you for taking the time to comment. May I suggest you point your doctor the blog post (if you have not yet done so) and see if that changes her/his mind. If your doctor is a member of (DNUK) am happy to email her/him the blog post and references.

  3. healthy tips March 5, 2013 at 07:15 #

    Great points altogether, you just won a new reader. What could you recommend in regards to your post that you simply made a few days in the past? Any certain?

  4. Swanson Vitamins March 6, 2013 at 04:56 #

    Way ta go pal! You really showed them!

  5. Vitamins and Minerals March 12, 2013 at 11:28 #

    I could relate entirely to what you were saying. You must of been reading my mind

  6. ageless male March 17, 2013 at 07:18 #

    Hi, I’ve been a lurker around your blog for a few months. I love this article and your entire site! Looking forward to reading more!

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  9. Jo June 11, 2013 at 15:58 #

    you are a very special doctor, special because you use your intelligence to go and look at the evidence out there and also intelligent because you know how to listen to your patients and take them seriously, you are not ‘blinded’ by all the bureaucracy which blinds all the other GPs/doctors out there, you were trained to be an independent practitioner to be a doctor, a doctor listens to the patient, looks at the patient ‘holistically’ keeps himself updated and looks out for an answer, what a shame there is so few of you left!

    I have pernicious anaemia, also had a gastric bypass in 2008, I was kept B12 deficient by my GP who can only see the BNF and NOTHING past it, 3 monthly B12 injections kept my B12 at 332 (in a range of 180 to 880), I was SEVERELY symptomatic, it took a private doctor to give me daily B12 injections and to recover from my symptoms, I still have some lingering symptoms probably because I was deficient for a while before being diagnosed and if I do not take my B12 injections daily my symptoms surely creep back quite quickly, yet my GP STILL refuses to prescribe my B12 any more often then 3 monthly and I have to buy it privately myself, including needles and syringes!

    I keep trying to fight this but so far have had no joy!

    My mother contracted Alzheimer’s disease at age 50 (so did my grandmother), she dies age 69 (so did my grandma coincidence), I was going through my mothers medical notes a few months ago and I discovered when she was in an ‘Alzheimer’s specialist centre’ she was tested for B12, she was SEVERELY deficient below the normal range, have they given it to her? NO! I am furious and I hurt inside, to know that some of my mother’s symptoms could have been alleviated and if B12 deficiency was discovered earlier she might have avoided dementia.

    I could go on forever but for now, THANK YOU for being such a brilliant doctor!


  1. Vitamin B12 deficiency particularly in vegetarians | delveinoneself - March 8, 2013

    […] Vitamin B12 deficiency – time for a rethink? ( […]

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