Dietary B12 is bound to proteins from which it is released by gastric acid, binds to haptocorrin from saliva, then travels to the ileum along with intrinsic factor secreted by the stomach. In the ileum B12 is released from haptocorrin and binds to intrinsic factor, and is absorbed as a B12-intrinsic factor complex by a receptor-mediated active process. B12 is transported in blood bound to transcobalamin and serum holotranscobalamin is an alternative biomarker for recent B12 intake. Read more about this on page 3.
At intakes above about 2.5 µg/day, the recommended intake (RDA), the B12-intrinsic factor complex becomes saturated so that the percent absorbed, by passive transport, falls to only ≈1% from doses above ≈25 µg/day. Nevertheless, high doses (500-1000 µg) are often used to maintain B12 status in people with no intrinsic factor due to pernicious anemia, or the elderly, as absorption of 1% of these high doses is sufficient. Alternatively, high doses of hydroxocobalamin or cyanocobalamin (1000 µg) can be given by intramuscular injection weekly, then monthly, if necessary.
Risks of deficiency
Globally the prevalence of vitamin B12 depletion and deficiency is high, primarily due to low intake of animal source foods which are the only natural source of the vitamin (1).
Low consumption of animal products occurs in many low income groups, and when such foods are avoided for cultural, religious or ethical reasons. Elderly persons may be more likely to be vitamin B12 deficient due to their having lower gastric acid and intrinsic factor, sometimes due to chronic, long-term infection with Helicobacter pylori. The autoimmune disease pernicious anaemia, which can occur at any age but has a higher prevalence in the elderly (2 to 4% after age 60 years), will also cause deficiency because in this disease there is a lack of the intrinsic factor required for B12 absorption. Other conditions which impair B12 absorption include Crohn disease, celiac disease, ileal bypass or resection, and gastric bypass or removal of part of the stomach. Unfortunately tests for B12 malabsorption are difficult and the only methods available today are based on the increase in serum holotranscobalamin after doses of B12 (the Cobasorb test) or administration of very low dose 14C-B12 (3, 4). B12 from supplements or fortified foods will be better absorbed than B12 from food if gastric acid is low, so this is sometimes a recommendation for elderly people.
Infants born to mothers deficient in B12 are born with low liver stores of the vitamin and then exposed to low levels in their mother’s milk; there are many case studies of infants presenting with severe growth and mental retardation around 3-4 months of age (5). High dose supplements to the infant resolve some but not always all of these problems.
Clinical symptoms of deficiency include changes in biomarkers in blood and urine (see page 3), followed by weakness and fatigue, neurological impairments such as peripheral neuropathy, reduced myelination and conductivity of neurons, megaloblastic anaemia, brain atrophy and dementia (1). Deficiency has to be relatively severe to produce megaloblastic anemia, so anemia is more common in strict vegetarians, those with malabsorptive conditions, and the elderly than in persons with a chronically low dietary intake. In fact, the functional consequences of subclinical cobalamin deficiency (called SCCD), which is generally diagnosed by biochemical tests, are not well defined. Importantly, one does not have to be a strict vegetarian to become depleted in B12; as the amount of any animal source food in the diet falls, then poorer B12 status will result (1).
Risks of excess
There are no known risks of consuming large amounts of vitamin B12 so consequently there are no upper limits to intake recommendations. When intakes are high absorption of a dose is <1% due to saturation of the intestinal receptors.
Medications that affect vitamin B12 absorption or metabolism include:
- Inhibitors of gastric acid secretion such as proton pump inhibitors (PPIs) and histamine receptor 2 antagonists, because gastric acid is needed to release the vitamin from food.
- Treatment of diabetes with metformin lowers serum B12. Initially this was thought to be a sign of B12 deficiency, but later research indicates that metformin causes the vitamin to accumulate in the liver.
- Chronic exposure to the anesthetic nitrous oxide, which oxidizes methylcobalamin.