Vitamin B12 - the consequences of deficiency - Dr Alan Stewart

You may wonder why I think it is worth devoting a whole piece to this single vitamin. Well, there is about to be an upsurge in the incidence of B12 deficiency, a deficiency which may cause permanent changes to the nervous system. Furthermore it would appear that many doctors and dietitians are not alive to some of the presentations of Vitamin B12 deficiency. Finally, if this readership is representative of the general population, then 1% or possibly more are on the verge of becoming deficient themselves.

Deficiency of this vitamin causes pernicious anaemia and other health problems related to the nervous system. Although deficiency has been fairly infrequent in the past it is becoming much more common because of a growth in two significant risk categories, the elderly and vegetarians/vegans.

Vitamin B12 has a complex chemical structure which contains one atom of the trace element cobalt at its centre. It is needed for the processing of enzymes involved in the synthesis of the amino acid methionine. Methionine is linked to the metabolism of folate and is necessary for blood formation and for methylation reactions. These involve the transfer of single carbon atoms within the body especially within the nervous system.

But it is also needed for the production of genetic material, DNA, needed by rapidly dividing and growing cells. Two main deficiency syndromes can develop.

ANAEMIA with the production of enlarged red blood cells - macrocytic anaemia. However this may not develop if the supply of folate is adequate. A good vegetarian or vegan diet with high intakes of green leafy vegetables or fortified breakfast cereals may minimise the risk of developing anaemia but will not prevent the neurological problems from evolving.

NEUROLOGICAL PROBLEMS come about because Vitamin B12 is needed by parts of the nervous system for the production of the protein associated with the myelin protective fatty sheath around nerve fibres as well as for the production of several chemicals within the nervous system. Deficiency can affect three parts of the nervous system: the peripheral nerves with loss of sensation and weakness in the legs, the spinal chord with loss of vibration and position sense in the legs resulting in unsteadiness, and parts of the brain resulting in mood change, loss of memory and early dementia.

Vitamin B12 is produced by bacteria and is found exclusively in animal products: liver, meats, eggs, dairy products and fish. There is virtually none in foods of vegetable origin. It is also produced by the bacteria in the large intestines but this is not absorbed into our bodies. To be absorbed the vitamin first has to be released from food by the action of pepsin and acid from the stomach. It then binds with a protein produced by the stomach called intrinsic factor. The complex passes through the intestines to the last twelve inches of the ileum, just before the commencement of the large bowel, where it is finally absorbed.

Only a limited amount, up to 2 micrograms can be absorbed after any one meal. It is absorbed into the blood stream and stored in the liver. In the elderly there is often a decrease in either the output of acid or intrinsic factor by the stomach and this will reduce the absorption of vitamin B12 even from an adequate diet.

The full deficiency state characterised by either anaemia or neurological changes usually evolves slowly over many months or years and thus the patient and his doctor may become accustomed to the symptoms which may then delay the diagnosis.

Recently it has been shown that genetic factors involving the related vitamin, folate, determines which pattern of deficiency symptoms will evolve. A common variant in the folate enzyme 5,10, hydroxymethylfolate reductase, which affects about 10% of the normal population, predisposes to the neurological manifestations predominating. Thus there is an important interaction between genetic and environmental factors determining the picture of deficiency even in elderly people.

Like many of the B vitamins, early features of deficiency are non-specific and include fatigue, depression, mood change and forgetfulness. These may be followed by weight loss, a sore, burning tongue, unsteadiness (especially in the dark) loss of feeling in the legs, and loss of the feeling of vibration particularly in the legs. Late symptoms include more severe mood changes, delusions and even dementia and by this time anaemia may also develop but it is not inevitable.

The anaemia worsens the fatigue and the patient, typically, develops a pale and sallow complexion. The patient will become bed bound, anaemic and depressed with little awareness of their plight.

The diagnosis is relatively easy, if it is thought of. A serum vitamin B12 is a simple, inexpensive test that is available at all district hospitals. Historically, because this deficiency was mainly seen in the elderly who often became anaemic, the deficiency state was referred to as "pernicious anaemia". Many doctors thus often just perform a blood test for anaemia. If the result is normal, it will falsely reassure them that the patient has both a sufficient supply of iron as well as vitamin B12 (and folate). Nowadays the majority of those with early or moderate vitamin B12 deficiency are not anaemic.
Consequently, once suspected, the only test for vitamin B12 is to measure the actual level in the blood.

In adults the amount needed to prevent or cure Vitamin B12 deficiency anaemia is very small, 1 microgram (one millionth of a gram) per 19, and this is the Lower Reference Nutrient Intake. Most omnivorous diets will easily provide more than this amount and exceed the Reference Nutrient Intake level of 1.5 micrograms. An increase of 0.5 micrograms per day is recommended during breast feeding.

The chance of risk should be small but appears to have risen. In most adults the risk of a low vitamin B12 is well below 1% of the normal population, but in the elderly aged 65 years and over this rises to an average of 5%, and even higher in those aged over 80 years. Only a few of these are actually anaemic but many are at risk of developing nervous system changes if untreated.

Amongst young people the risk of deficiency is no longer small. In girls aged 14 to 18 years 8% have low blood levels and, of these, 3% are low enough to cause potentially irreversible damage to the growing brain. A vegetarian diet and possibly the oral contraceptive pill would seem to be the main risk factors.
If these girls do not change their diets and, some years later, become pregnant then there is a very real risk of their offspring becoming vitamin B12 deficient with disastrous consequences for growth and brain development. Hidden genetic factors may also predispose to deficiency.

At present serious thought is being given to fortifying certain staple foods with folate to help improve the levels of many young women who may become pregnant. Folate supplementation before and during the early part of pregnancy reduces the risk of spina bifida and other neurological problems. For poorly fed vegetarians and vegans there may also be a real need for improvement in vitamin B12 status before conception.

For the elderly their doctor will need to be alert to the early features of deficiency and, because of the lasting and serious effects of deficiency, should not hesitate to test the vitamin B12 level.

1. Human Nutrition and Dietetics. Edited by Garrow JS, James WPT & Ralph A. 10th Edition. Churchill Livingstone. Edinburgh 2000.
2. Department of Health and Social Security. Report on Health and Social Subjects: 41. Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. HMSO 1991.
3. Gregory J. et al. National Diet and Nutrition Survey: young people aged four to eighteen years. The Stationery Office. London 2000.
4. National Diet and Nutritional Survey; Older people aged 65 years and older. The Stationery Office. London 1997.

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First Published in 2001

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