What causes B12 deficiency?

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Submitted by HugoMinney on Sun, 08/07/2011 - 00:00

Vitamin B12 is a water-soluble vitamin, like Vitamin C.  You need to eat Vitamin C regularly, so you need to take Vitamin B12 regularly too.  B12 is so important though, that your body 'scavenges' it very efficiently, so you might think you are doing fine when actually your body is working very hard to keep enough B12.  Like the swan - serene on top of the water, but paddling like mad underneath.

You need B12 for some really important body functions.  
It's used for lipid metabolism.  This means that if you don't have enough B12, then your nerves won't be able to conduct signals (so you'll find you can't move muscles, can't feel / get pins and needles / get numbness, suffer confusion and memory loss, get "the fogs" when you feel as though you are isolated from everyone); it also means your hormones may go funny, your immune system starts to pack up and you get autoimmune diseases, your digestion may develop problems, etc.
B12 is used by DNA during cell growth and replication (body growth) and to turn genes on and off.  
B12 is very important for energy production - so without it you can start to feel really tired (often diagnosed as ME or CFS).
 
The really important thing is that animals can’t make vitamin B12 - we have to eat it from animals that have lots of bacteria in their gut, such as cows, sheep and so on.  Yes we do have bacteria in our gut, but too low down for us to absorb the B12 (check out Gruesome facts!). That means red meat, and especially liver.  Marmite is a good source for vegetarians, which is essentially bacteria stew.
There are two main causes of Vitamin B12 deficiency
  • not getting B12 from your diet;
  • getting B12 but not being able to use it.
Both can happen suddenly or can take years or even decades (eg a vegetarian typically won't develop B12 deficiency for 10-15 years after they become vegetarian, because the body 'scavenges' so efficiently).

B12 is safe, cheap and easy to obtain. It's a nutritional supplement, and doesn't interfere with any medication; it does seem to cure a lot of modern syndromes, so people stop needing medication.  BUT DON'T STOP YOUR MEDICATION UNTIL YOUR DOCTOR SAYS YOU DON'T NEED IT.  When the symptoms go away, that's the time to stop the medication, not before.

Who gets B12 deficiency?

We think that 2 in 5 people (40%) of people are at risk of B12 deficiency, and probably 1 in 5 (18% in our neck of the woods) have it.  That's a lot of people.  They suffer from a whole lot of non-specific symptoms such as tiredness, confusion, pains, loss of power eg not being able to walk, etc.  I personally think that modern agricultural methods mean there's less in the food, and I'm checking out some ONS statistics to find out if this is true. But if you are older, suffering from renal imbalance or diabetes, or have had any gastrointestinal surgery, then you may not be able to take it in from the food you eat, and may need more.

What food should it be in?

Vitamin B12 is manufactured by bacteria in animal guts, so you should be able to get it from red meat, all meat including fish, and dairy products. However with modern farming methods there may be a shortage in the meat as well.

What diseases could a B12 deficiency cause?

Vitamin B12 is very important to the body, and deficiency could cause a whole lot of symptoms, many of which are misdiagnosed as other diseases such as Anaemia, Multiple Sclerosis-like presentations, Depression, Confusion, M.E., Neuralgia – we’ve dedicated a page to each please see the menu on the left. Note that Pernicious Anaemia is not a misdiagnosis – Pernicious Anaemia (PA) is always caused by vitamin B12 deficiency and will always make vitamin B12 deficiency worse. Please do check that you are getting the right care – go to your doctor to make sure you haven’t missed something obvious and important such as cancer. Vitamin B12 may be able to influence the development of cancer too.

What does B12 look like, and why?

B12 consists of an amine ring, and is vital for life (it's a Vit-amine! yes that's really where the word came from!).

it is one of the biggest food molecules that we absorb (proteins and lipids are broken down into small units so they can be absorbed).  It has a cobalt metal ion in the middle which is how it works, with the amine ring around the cobalt, and a tail on the far side to protect the cobalt ion at the back.

Structure of B12 molecule - subject to copyright

The Cobalt has a +ve charge and a particular amount of space/ hydrophilic/ hydrophobic collar, so it can attach to various molecules.

For example, B12 can stick to cyanide and heavy metals (and peroxide), and in this combination it gets to the kidney, the kidney is looking out for it, and it goes into the urine.  If you drink too much alcohol or smoke, chances are your B12 is draining out of your body as it works hard to take the toxins out.

It combines with a hydroxy group (the usual form sold for human use), withe a methyl group (which is very important for DNA and is easy to change for other things in the body) and an adenosyl group (used in the energy cycles).  It is an extremely useful molecule.

Here's the textbook stuff

Vitamin B12 is an essential nutrient available exclusively from bacterial sources, ie in the diet,  or through the action of gut bacteria [1] (see “where does B12  come from?”)

  It is a fairly large molecule consisting of amine rings with a cobalt molecule in the middle (molecular weight 1355.5) and so the process of digestion, absorption, transportation, conveyance into the cell, and utilisation by the cell is necessarily complex and problems can occur at many points in these pathways.

Problems can occur with:

Problem Occurs

 

Observe

Inadequate Intake

B12 is found in liver and to a lesser extent all animal products (see “where does B12 come from?”)

Vegetarian and vegan diets should be supplemented with yeast or B12 vitamin supplements

Many modern diets have the vitamins processed out of them, especially the water soluble vitamins (C and B12 along with the other B vitamins). 

B12 producing bacteria should be present in the gut, but modern eating habits do not encourage the ingestion of live bacteria <see notes on TransHepatoCirculation>

Some questions have been raised about cobalt in soil affecting B12 levels in animals grazing the soil and subsequently available to humans

May also be recorded as adequate in diet (may detect B12 but not a biologically useable form) but blood serum levels will be low or low normal

The Schilling test (provision of tracer B12 – usually in the form of mildly radioactive B12) tests for the ability of the gut to absorb B12 but does not take into account any further stages in the use of B12 .  The Schilling test is largely out of use now.

Malabsorption from diet

Defective release of cobalamin from food

1)    Gastric achlorhydria (failure to produce acid needed for digestion)

2)    Partial gastrectomy

3)    Drugs that block acid secretion (PPI, H2 blockers, etc)

4)    Defective release can be exacerbated by environmental factors such as Nitrous oxide, alcohol, by-products of smoking tobacco

 

Absence of Intrinsic Factor (which enables the absorption of B12 through the intestinal wall) – could be congenital or caused by auto-immune disease

Autoimmune disease can be detected by looking for Intrinsic Factor (IF) antibodies or Parietal Cell antibodies (Parietal Cells are the cells that manufacture stomach acid).  Diseases like MS are autoimmune diseases

Receptors are needed to transport the hydroxyl-B12 (or cyano-B12 if using artificial supplements) across the intestine wall

 

There are a whole lot of genetic abnormalities of haptocorrins (the TransCobalamins – the proteins that transport B12 across the intestine wall, around the blood stream and into the tissues) which could cause this

Disorders of terminal ileum

1)    Tropical Sprue/ non Tropical Sprue

2)    Regional enteritis

3)    Intestinal resection

4)    Neoplasm and granulomatous disorders

Competition eg Fish tape worm, bacteria

Other pathogens eg Giardia lamblia

Drugs such as P. Aminosalicylic acid, colchicines, neomycin

Tropical sprue and non-tropical sprue may be caused if the colon (the last part of the intestine) microbes manage to get into the small intestine (where most of the food is absorbed).  The exact mechanism isn’t known but it could be that these bacteria produce a different form of vitamin B12 which can’t be used by humans and other mammals.

 

Some studies have also noted that heavy infestation with Giardia parasite can also cause intestinal malabsorption (thanks to a web site reader for this!)

Transport and conversion

Trans-cobalamin II complex are needed to transport B12 to the tissues around the body to be utilised for cell maturation and function

Normal or high levels of B12 in the blood may be recorded where:

  • Forms of B12 which cannot be used are present
  • IF antibody may interfere with the usability of serum B12[2]

Utilisation in the cell

Failure to convert from hydroxyl to active forms for use in cells

May exhibit normal or high blood serum levels but patient still exhibits neurological symptoms

Levels of homocystine in the blood may also be tested as methyl-B12 converts this ‘bad mood’ chemical to a protein required for the body; but this test is far from specific and not accurate for B12 deficiency

This table based on [3]

Vitamin B12 absorption Am Fam Phys

Diagram from [4]

Classic Addisonian symptoms (macrocytosis or oversized red blood cells)[5] will be rare nowadays because food fortification and supplementation with folic acid (B9 – sometimes also called Vitamin M) masks/ corrects the macrocytosis even when B12 deficiency is present.

 

Citations

 

1.         Markle, H.V., Cobalamin. Crit Rev Clin Lab Sci, 1996. 33(4): p. 247-356.

2.         Hamilton, M.S., S. Blackmore, and A. Lee, Possible cause of false normal B-12 assays. BMJ, 2006. 333(7569): p. 654-5.

3.         Baboir, B.M. and H.F. Bunn, Pernicious Anaemia, in Harrison's Principles of Internal Medicine. 2005. p. 601-607.

4.         Oh, R. and D.L. Brown, Vitamin B12 deficiency. Am Fam Physician, 2003. 67(5): p. 979-86.

5.         Biermer, A., Über eine Form von progressiver perniciöser Anämie. Correspondenz-Blatt Schw. Ärzte., 1872. 2: p. 15-17.

 

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