B12 deficiency linked with brain shrinkage in later life

Vitamin B12 is a nutrient found naturally in animal products such as meat, fish and eggs. The nutrient is perhaps best known for its relationship with a condition known as ‘pernicious anaemia’ – a form of anaemia caused by B12 deficiency which itself is caused by impaired absorption of B12 from the gut. However, for some time now there has been specific interest in the role the B12 plays in brain function. In particular, B12 deficiency is believed to play a potential role in the declining brain function (cognitive impairment) often seen in ageing.

One of the proposed mechanisms here concerns ‘homocysteine’ – an amino acid that is linked with adverse effects on health including cardiovascular issues such as heart disease and stroke. Low levels of B12 can cause raised levels of homocysteine (as can low levels of other nutrients including folic acid and vitamin B6). Measuring homocysteine levels is sometimes used as a proxy for B12 status.

In a study published this week in the journal Neurology, vitamin B12 levels and brain structure and function was assessed in a group of individuals aged 65 or more. B12 status was assessed with five tests including homocysteine levels and serum (blood) B12 levels. Four and a half years later, the individuals were assessed via tests for cognitive function as well as MRIs of the brain.

In general, tests which indicated low B12 status (e.g. raised homocysteine levels) were associated with lower cognitive function tests scores and smaller brain volume. This was true for all of the 5 markers for B12 except serum B12 levels.

What this evidence suggests is that B12 may have an important role to play in the ageing brain, and that assessing levels via the standard blood test is not particularly useful.

This situation is reminiscent of tests for iron levels in the body. Serum iron is a generally useless test of actual iron levels in the body, while other tests (notably ‘ferritin’) are much more useful in practice.

The absorption of B12 is a quite complex process, and ageing may well lead to an impairment of B12 absorption and increase the risk of deficiency. There is a risk, of course, that using the most common test for B12 levels (serum B12) runs the risk of missing genuine B12 deficiency. The end result might be someone languishing in a B12-deficient state, which may have profound implications for their health and wellbeing.

For more information about B12 deficiency and how to assess this you might like to listen to this podcast featuring Sally Pacholok, author of the book ‘Could it be B12?’. You can learn more about the book here.


1. Tangney CC, et al. Vitamin B12, cognition, and brain MRI measures – A cross-sectional examination. Neurology 2011;77(13):1276-1282

9 Responses to B12 deficiency linked with brain shrinkage in later life

  1. audrey wickham 30 September 2011 at 5:50 pm #

    thank you for this piece on B12. It would have helped if you had mentioned the tests that do show up the deficiency.

  2. Angelica 30 September 2011 at 11:32 pm #

    i have hyper homocysteine (for which i was advised to take folic acid daily until a couple of weeks ago when my doc told me to stop as new research shows it is not good to do that ?).
    i also have low ferritin stores.
    i am not elderly.
    does your post mean i should start taking b12?
    i have so little info on the effects of hyper homocysteine itself that any scraps of info help!

  3. Fei 1 October 2011 at 12:55 am #

    Dr. Briffa,
    What should we learn from this study?
    1. Should we eat as much meat, fish, and eggs as possible? or just eat regularly? or
    2. should we take B12 supplement?
    3. what’s the normal range of B12 level? is the recommended normal range adequate to your opinion?

    What action should we take based on this study?

  4. Brain Surgeon 1 October 2011 at 8:15 am #

    vitamin b12 is important in making our brain and nervous system function properly, for this to eat a decent amount of fish, meat, poultry or dairy products regularly….Really i liked your site and your article also.. today i want to tweet this post and share on facebook..Thanks and i hope you will be provide such type of articles

  5. Chris 1 October 2011 at 4:54 pm #

    Kilmer McCully is the learned gent who slogged against the odds to elucidate theories upon homocysteine and offer those theories to others. The ‘reaction’ of ‘others’ in the main was not sufficiently open-minded nor progressive to serve the interests of open debate as part of the evolutionary process of progress in science. His book on the subject, ‘The Homocysteine Revolution’ is an excellent read and might be a good place, Angelica, to enter into the subject.

    Kilmer McCully presents his homocysteine hypothesis as an alternative to the revered orthodoxy of the diet-heart hypothesis which proponents say explains the etiology (cause(s)) of heart disease – and which a group of cholesterol sceptic individuals say doesn’t. Dr McCully seems to be held in high regard by those of the cholesterol sceptics I have read.

    Another interesting read would be ‘The Statin Damage Crisis’ (Dr Duane Graveline). Graveline incorporates aspects of Dr McCullys’ homocysteine lowering protocols into his alternative treatment plan for mitigating risk(s) of, or from, heart disease. McCully suggests deficiencies of B6, B12, and folic acid, may have a part in decreased capacity to clear away ‘surplus’ homocysteine; each author discusses the merits of addressing such deficiencies with diet and supplements.

    ‘The Homocysteine Revolution’ left me with an impression (a cursory view and not a critical one) that B6 deficiency may have the strongest association to elevated homocysteine.

    Angelica, what condition does your Doc think lies at the cause of your hyper homocysteine and what potential complications does your Doc feel (s)he is treating? This is important for you to be clear upon.

    We’ve heard a lot about folic acid deficiency over two or more decades. Can you track to the ‘new research’ that suggests folic acid supplementation is no longer such a good idea? Who commissioned or conducted the research and most importantly who financed it?

    It’s worth getting a little involved to become better informed about the topic but the more informed one becomes the more involved the topic becomes! Whatever is our understanding of the workings of the human body we’re always going to find in time that matters are a ‘little bit more complicated than that’ (something proponents of the diet-heart hypothesis should bear in mind). There’s no substitute for a proper consultation with your Doc, but the value of that consultation can be improved if you have troubled to bring some of your understanding up to his or her level. You’ll get better value if you are active in the exchange as opposed to passive. Possibly your Doc is old school and has not considered that cholesterol itself may be fairly innocuous but oxidised cholesterol can be harmful, and (s)he may not be versed in the theory that hyper homocsyteine may play a part in the oxidation of cholesterol [1].

    Natural levels of cholesterol (I mean lipoproteins really) and homocyteine might vary between individuals. “Jack Sprat could eat no fat. His wife could eat no lean. And so between them both, you see, They licked the platter clean.” As far ago as the sixteenth century, folks recognised that individuals share similarities but nature imposes that we are not all the same.

    McCully is your man to begin with. He’s also authored ‘The Heart Revolution’ (that my postie delivered while I composed this comment (!)). In a restricted and specific sense you may end up better informed than your GP, but, your GP will always have a helpful and expansive outlook on issues that is crucial to primary care.

  6. Chris 1 October 2011 at 5:29 pm #

    1, The Heart Revolution: Dr Kilmer McCully, p20 “The Evil Twins: Cholesterol and Oxy-Cholesterol”

    “.. The cholesterol we get in meat, eggs, and other foods is highly pure until heated or processed, when some of the pure cholesterol converts to [one or other of the forms of] oxy-cholesterol. Fried foods, powdered milk, and spray dried-eggs all contain these dangerous oxy-cholesterols.
    “There is a second source of oxy-cholesterols within the body. Homocysteine helps to form these damaging substances within the cells of the arteries, leading to placques. It’s not enough to simply avoid foods containing oxy-cholesterol, although certainly you should. You also want a low homocysteine level so that less oxy-cholesterol is formed in the body.”

    Human breast milk is rich in cholesterol. Cows milk is rich in cholesterol. Egg yolks are rich in cholesterol. It evidently takes a lot of cholesterol to make a healthy chicken, a lot of cholesterol to build a healthy calf, and a lot of cholesterol to nurture a healthy human infant. Chickens are a bird and birds are descended from dinosaurs.

    If we could lay our hands upon a ‘fresh’ dinosaur egg what do you suppose we might discover? And if we analysed the ‘cholesterol’ in infant formula what might we likely discover? Please, tempting as it is, do not rush to conclusions; that’s not the way that science should progress, albeit that it seems that it has.

  7. Cordier 2 October 2011 at 11:08 am #

    The diabetic state can be an underhanded trap: “functional vitamin B12 deficiency”


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