Prepared on 24 March 2003, Derrick Garwood, Freelance Medical Writer and Editor

Until the early years of the last century, pernicious anaemia was invariably fatal, but in 1926 Georges Minot and William Murphy found that the condition could be reversed by eating large quantities of raw liver – a fate which is arguably almost as bad! In sufferers, insufficient vitamin B12 is absorbed, leading to increased destruction of red blood cells and megaloblastic anaemia, as well as neurological symptoms - for more information on symptoms click here. Clinical photographs can be found here.

As vitamin B12 is only found in foods of animal origin, vegan and vegetarian diets can give rise to dietary deficiency, but a more common cause is lack of intrinsic factor, a protein secreted by the gastric mucosa which enables the vitamin to be absorbed. The overall incidence of pernicious anaemia is about 1 in 1000 individuals, but higher among people of Northern European descent, and the average age at diagnosis is 60. Many researchers believe an autoimmune reaction which destroys the cells that secrete intrinsic factor is responsible.

Vitamin B12, or cobalamin, is synthesised exclusively by microorganisms and found in the liver of animals, where it is bound to protein. Once it has been absorbed by the human gut it is transported to the liver, which can store up to six years' supply, so dietary deficiencies are in fact rare. When the body has an insufficient quantity, anaemia results from impaired DNA synthesis, and neurological complications are caused by the progressive demyelination of neurones. For a description of the biochemical processes involved, click here.

The cobalt ion in the centre of the vitamin B12 molecule is responsible for its physiological activity. The adult body contains about 10 mg of cobalt, including 2 mg in the liver, and the average intake is 7 - 30 mg/day. As an interesting but irrelevant diversion, inorganic cobalt is used to stabilise beer, but the synergistic effect of cobalt and alcohol can lead to heart failure in heavy consumers!

Before examining the effects of pernicious anaemia in more detail, it might be useful to look at the process of red blood cell production, or erythropoiesis. It takes four days for haematocytes in the bone marrow to become mature erythrocytes, which live for about 120 days in the circulation. As they do not have a nucleus they cannot divide or synthesise new cellular components, so degenerate from ageing or damage, and 2.5 million are destroyed every second.

With the advent of new markers for intracellular functional deficiency, namely methylmalonic acid (MMA) and homocysteine (tHcy), it has now become clear that anaemia is just one of many signs and symptoms of B12 deficiency, and may not be present at all. Moreover, true pernicious anaemia caused by a lack of intrinsic factor constitutes only a small fraction of cases; far more common may be malabsorption resulting from mild or moderate atrophic gastritis as a result of decreased secretion of gastric acid. It has been suggested that Helicobacter pylori infection is involved in the pathogenesis of this condition – see the second abstract at ktc.com.

There are endoscope pictures of atrophic gastritis at, but it is not easy to identify. Many lifestyle factors, such as smoking and high alcohol consumption, also affect the individual's cobalamin status.

The HoloTC.net site has an extensive section on the effects of B12 deficiency, pointing out that its earliest manifestation may be diffuse neuropsychiatric symptoms, which can be easily overlooked. These include confusion, memory disturbances, depression, mood swings and personality changes. Interestingly, elderly people often have reduced vitamin B12 levels and these are a frequent finding in patients with Alzheimer's Disease.

Vegetarians and vegans are particularly concerned about maintaining an adequate intake of cobalamin, and the Vegetarian Network Victoria site incorporates some valuable dietary information. For example, edible seaweeds and fermented soy products have been promoted as good sources of B12, but they actually contain B12 analogues. These have a similar structure but can block the absorption of cobalamin and reduce its availability. Also, a high intake of Vitamin C can have a similar effect by converting B12 in the diet to an inactive form.

The only reliable sources of cobalamin for vegans are vitamin B12 supplements and foods fortified with B12 – many consume sufficient to avoid pernicious anaemia but not to minimise the potential risk of heart disease, stroke or pregnancy complications - see the Vegetarian Network Victoria site. This is because repeated observations have shown vegans to have elevated homocysteine levels, which are associated with the above conditions. As this vitamin is more effective when taken in small amounts, the following guidelines are recommended:

• eat fortified foods two or three times each day to provide 3 mg/day

• take a daily 10 mg supplement

• take a weekly 2000 mg supplement.

It is also possible to develop pernicious anaemia whilst having an adequate diet and absorbing plentiful amounts of B12 – by becoming infected with a broad fish tapeworm of the family Diphyllobothriidae. These have a complex life cycle involving two intermediate hosts, one of which is a freshwater fish, and various definitive fish-eating hosts, including man. The tapeworm, which can reach 10 m in length, selectively takes up B12, competing with the host for the vitamin. It may also interfere with the host's absorption process. Therefore, pernicious anaemia prevention ought really to include avoiding consumption of raw freshwater fish!

This tour was submitted by Derrick Garwood, a Freelance Medical Writer and Editor.

The details presented here were accurate at the time of publication, but remember that information on the Web has a tendency to change without notice!

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