Vitamin B12 deficiency is most commonly caused by a lack of intrinsic factor - a substance produced in the stomach that is necessary for the absorption of vitamin B12 from food. When intrinsic factor is lacking, vitamin B12 is unable to be absorbed and is therefore unable to be utilised by the body. Pernicious anaemia is one such condition where the production of intrinsic factor is impaired. It is a leading cause of vitamin B12 deficiency. Other causes of vitamin B12 deficiency include: A diet inadequate in vitamin B12 rich foods - particularly so in vegetarians who don’t eat any animal products, meat, fish, milk, eggs, butter, cheese and other dairy products (vegans) Inadequate absorption or utilisation of B12 because of gastric abnormalities such as coeliac disease, inflammation of the stomach (gastritis), or pancreatic insufficiency Inadequate absorption can also occur after stomach and intestinal surgery as well as in inflammatory bowel diseases like Crohn's disease
An increase in certain intestinal organisms Drugs that may interfere with the absorption of vitamin B12 Symptoms of vitamin B12 deficiency usually don’t appear for at least two years. The reason for this is that a large amount of vitamin B12 is usually stored by the liver. Most people, apart from vegans, have a three to five year supply in their bodies. Initial symptoms of vitamin B12 deficiency can include: If left untreated vitamin B12 deficiency can cause progressive damage to the nervous system, especially the nerves outside the brain and spinal cord. When the spinal cord is involved, the first symptoms include difficulty in feeling vibrations in the feet, loss of position sense, and loss of muscle co-ordination (ataxia). Other symptoms of untreated vitamin B12 deficiency may include: An enlarged spleen and liver (hepatosplenomegaly) Mild depression and confusion Hallucinations, personality and mood changes Damage to the optic nerve. Side effects of vitamin B12 supplementation
Vitamin-B12 (B12) deficiency is seen in two populations: those with food-bound B12 malabsorption and those with inadequate dietary B12 intake (common in populations with low or non-meat eating dietary practices).1 In the first situation, traditional treatment has been high-dose intramuscular (IM) B12 injections2 and in the second situation oral supplementation is a logical treatment. In practice, however, a number of these people are also being treated with IM B12 injections. Is this practice appropriate? Vitamin B12 deficiency is important to treat, or ideally prevent, as it is associated with the risk of megaloblastic anaemia plus cognitive and neurological deficits.3,4 Even with borderline B12 deficiency, concentrations of the metabolite homocysteine, a documented risk factor for cardiovascular disease, are increased.5,6 B12 interacts with folate in critical metabolic pathways; they are co-factors in the ubiquitous one-carbon metabolism and the balance between these two co-factors is important.3,5Elevated levels of folate can intensify the physiological effects of B12 deficiency more than if folate levels were normal and B12 levels low.3 Of particular concern are the effects of raised homocysteine concentrations and B12/folate imbalances on pregnancy outcomes such as early pregnancy loss
, prematurity, low birth weight7 and neural tube defects.7,8 Clinicians are aware that folic acid supplementation in pregnancy is important to reduce the risk of birth defects, but it is not well recognised that if a woman has low B12 stores, giving folic acid augments the effects of low B12 on the foetus.6 Maternal B12 deficiency predicts increased abdominal adiposity, early signs of insulin resistance,9 and diminished cognitive performance in offspring.4 These effects are more pronounced with high maternal folate and low B12.9 In the opposite situation of relative B12 excess, it is not known if there are adverse effects. However, it would seem prudent to avoid increasing B12 concentrations much higher than is physiologically required. In a current AUT University study (ANZCTR:ACTRN12610000262000) investigating the efficacy of oral B12 supplementation for Indian women of child-bearing age, 5 out of 63 women were withdrawn or excluded because they received out of protocol IM B12 injections by their general practitioner.
Following administration of the IM injections, serum B12 measurements exceeded 1476 mcg (the maximum laboratory measurement limit and significantly above the 800 mcg upper limit of normal). One woman reported persistence of this elevated serum B12 measurement at 18 months after injections. The recommended dietary intake for B12 is 2.4 mcg/day.10 In B12 deficiency due to inadequate intake, transport proteins for B12 absorption are increased and enterohepatic recycling of B12 is more efficient. B12 deficiency from inadequate intake is not as profound as deficiency secondary to B12 malabsorption.1 When gastrointestinal absorption of B12 is intact, increased dietary intake of B12 or low-dose oral B12 supplements are effective to increase serum B12. In a 2009 study on oral B12 supplementation in India, daily doses of 2 mcg and 10 mcg over a 12-month period resulted in 64% and 119% increases respectively in serum B12 with a large reduction in homocysteine concentrations.6 Research evidence supports the therapeutic efficacy of oral B12 supplements (commonly cyanocobalamin) for treating deficiency, even in those with B12 malabsorption.2 Transport proteins, such as intrinsic factor, are required to absorb 95–99% of a physiological load of B12 (1.5–3 mcg), while the balance is absorbed by passive diffusion.1,2 Transport proteins for vitamin B12 are fully saturated at approximately 1.5–3 mcg
, but the amount absorbed via passive diffusion increases with higher doses.1 Even with malabsorption, sufficient B12 can be absorbed orally via passive diffusion if the dose is high enough.2 Unlike food-derived B12 which is released from the food matrix by acid hydrolysis, cyanocobalamin exists as free B12. This is advantageous for people with low levels of gastric acid and food-bound B12 malabsorption (the commonest form of B12 malabsorption).1 Changing cultural demographics in New Zealand, trends towards vegetarian or vegan dietary preferences and the high costs of meat, fish and dairy products all exacerbate the population-risk of B12 deficiency secondary to inadequate intake. It is important to consider whether inadequate intake is the cause of B12 deficiency. If so, then low-dose oral supplements and dietary advice to increase B12 intake are more appropriate than high-dose B12 injections. Issues such as low compliance with oral supplements or dietary advice, a preference for IM injections and the lack of a PHARMAC-funded oral B12 supplement need consideration.