New information about Vitamin B12 Deficiency



Type one diabetics are prone to B12 deficiency because of their increased risk of getting autoimmune disorders. Type two diabetics may get it due to the effect of metformin on B12 absorption.  The BMJ published an article about B12 deficiency and I am summarising it here because there is some important new information for doctors and patients.

The main new information that diagnosis is not as straightforward as the blood test because deficiency can occur and cause symptoms even when the levels are in the normal range. Also some symptoms won’t reverse if they are not treated within the first six months after presentation.

On the positive side, some people are able to take oral B12 quite successfully and may not need injections of B12 for the rest of their lives.

B12 deficiency affects DNA and cell metabolism. B12 is only available naturally from animal products. Because the body stores B12 pretty well, deficiency may not produce symptoms for several years, after going on a strict vegan diet for instance.

In the UK and USA around 6% of under 60s are deficient and 20% of those over 60 are too. In poorer countries deficiency is much more common, possibly reflecting the relative lack of meat in the diet.

Dietary B12 binds to intrinsic factor in the stomach and small bowel to allow absorption into the blood stream.  In pernicious anaemia the stomach cells die off.  Certain drugs can also affect B12 absorption including high dose proton pump inhibitors eg lansoprazole and omeprazole.  Other factors can be alcohol, slow K and cholestyramine.

The first symptoms to show up are often fatigue and anaemia. Moderate impairment can show up as an anaemia with bigger red cells, a swollen red tongue and reduced feeling in the fingers and toes. Severe impairment can show bone marrow suppression, neurological problems and cardiomyopathy. However B12 deficiency can occur with blood levels in the normal range and without anaemia. The cells may be of normal size if there is also iron deficiency at the same time.

Other types of blood cells can be affected in severe deficiency including the white cells and platelets.

The skin pigment can become deeper, reproduction affected, and osteoporosis can occur.

Neurologically motor disturbance, sensory loss, poor balance and reflexes, cognitive impairment and memory loss can occur. Some people may even be psychotic. Even at these extremes 20% of sufferers are not anaemic. Patients may say that their coordination is off, they have become clumsy and can’t walk right. Without treatment weakness and stiffness may develop. Damage to peripheral nerves causes sleepiness, altered taste and smell and damage to the optic nerve.  In severe stages a dementia like illness can occur with hallucinations, paranoia and severe depression.

The main test for deficiency is the cobalamin level but several other tests are also available. None are perfect. B12 levels are often tested when macrocytic anaemia is detected. People with levels of 148 pmol or in the USA 200ng/L or under represent an estimated 97% of people with the condition. This will leave a few, potentially with the condition but who are harder to diagnose. The authors state, “It is not clear what level of serum cobalamin may represent subclinical deficiency.”

Holotranscobalamin and methylmalonic acid levels may be better here but are specialist tests. Homocysteine levels may be used but the test is less specific and raised levels can occur in other conditions.

If B12 deficiency is found and there is no dietary lack of animal products tests for intrinsic factor and anti-parietal cell antibodies are usually done to identify the autoimmune condition pernicious anaemia.

Treatment is started as soon as possible particularly if there is neurological symptoms. Usually this is 1000 units intramuscularly on alternate days for up to three weeks or until there is no further improvement. For irreversible causes eg pernicious anaemia the injections continue for life, usually at 3 monthly intervals.

Oral treatment can be given in a dose of 5-150 units a day very successfully particularly in mild deficiency when the person can be trusted to take them. Potassium requirements may go up in the early phases of treatment as red cells are replenished. Folic acid and iron may also be required.

Although improvement in blood measurements is usually rapid taking days or weeks, neurological improvement can take up to three months but damage can be irreversible if treatment is not started within six months of onset.

Although pernicious anaemia is not preventable, deficiency due to vegan diets, metformin and proton pump inhibitors are. The oral form can work well here.

Summarised from Vitamin B12 deficiency. Alesia Hunt, Dominic Harrington, Susan Robinson.

BMJ 6th September 2014



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