Cobalamin (vitamin B12) Deficiency
Cobalamin (vitamin B12) Deficiency
By Renata Trister DO
According to data obtained in the Tufts University Framingham Offspring Study suggests that nearly 40% of people (ages 25-83) have plasma B12 levels in the low normal range. 9% had a significant deficiency and 16% had a near deficiency. Even a mild vitamin B-12 deficiency is associated with a greater risk for accelerated cognitive decline.
B12 deficiency has been estimated to affect about 40% of people over 60 years of age. In these patients, some of the symptoms we attribute to “normal aging” such as cognitive decline and memory loss may in part be caused or exacerbated by B12 deficiency.
Vitamin B12 works together with folate in the synthesis of DNA and red blood cells. It’s also involved in the production of the myelin sheath around the nerves, and the conduction of nerve impulses.
Dietary sources and availability
Microorganisms such as bacteria and algae synthesize and are the source of vitamin B12. The vitamin made by these microorganisms enters the human food chain through incorporation into food of animal origin. In vegetarian/ruminating animals, gastrointestinal fermentation supports the growth of these vitamin B12-synthesising microorganisms. The vitamin is absorbed and incorporated into their tissues. Omnivores and carnivores derive dietary vitamin B12 from animal products (i.e., milk, cheese, eggs, meat).
The absorption of vitamin B12 in humans is complex. Vitamin B12 in food is bound to proteins. The hydrochloric acid present in the stomach cleaves B12 from these proteins. The free form of the vitamin is immediately bound to glycoproteins called R-binders /haptocorrins. This protects B12 from denaturation in the stomach. Intrinsic factor, secreted by parietal cells in the stomach, binds vitamin B12 and enables its active absorption. When the contents of the stomach enter the duodenum, the R-binders become partly digested by the pancreatic proteases, release vitamin B12. The pH in the duodenum is more neutral than that in the stomach, the intrinsic factor has a high binding affinity to vitamin B12, and it quickly binds the vitamin as. The vitamin B12-intrinsic factor complex then proceeds to the lower end of the small intestine, where it is absorbed by phagocytosis by specific ileal receptors.
Over the last 10 years several definitions of Cobalamin deficiency have been published. Cobalamin metabolism is complex and involves a series of processes. A dysfunction in any of these processes can result in a deficiency. The main causes of Cobalamin deficiency are food-cobalamin malabsorption (50%), pernicious anemia (30%), insufficient nutritional vitamin B12 intake (7%) and malabsorption (5%). Dietary causes of the deficiency are found in malnourished elderly people and in strict vegetarians while malabsorption occurs in patients suffering from several gastrointestinal conditions.
Vitamin B12 is an important co-enzyme required for the production of tetra-hydrofolate, which is necessary for proper DNA synthesis. B12 deficiency results in impaired DNA formation and consequent retardation of cell division. This process results in the formation of megaloblastic cells especially in tissues with rapid turnover such as hematopoietic cells and intestinal epithelial cells.
Although measurement of vitamin B12 levels is the gold standard for the diagnosis of B12 deficiency some reports do exist concerning difficulties in its assay. The availability of vitamin B12 depends on its absorption from the ileum and its transport in blood to the liver and bone marrow by a carrier protein called transcobalamin. Circulating vitamin B12 is bound to 2 proteins, haptocorrin and transcobalamin.
Many case reports of normal plasma cobalamin levels in patients with clinical signs of vitamin B12 deficiency and a response to treatment with the vitamin.
B12 deficiency is often missed for two reasons. First, it’s not routinely tested for. Second, the low end of the laboratory reference range may be too low. Many B12 deficient people have so-called “normal” levels of B12.
Severe B12 deficiency – pernicious anemia (an autoimmune condition where the body destroys intrinsic factor, a protein for the absorption of B12). Anemia is the final stage of B12 deficiency. Long before anemia, B12 deficiency causes several other problems, including fatigue, lethargy, weakness, memory loss and neurological and psychiatric problems.
Causes of B12 malabsorption include:
• Intestinal dysbiosis
• Leaky gut and/or gut inflammation
• Atrophic gastritis or hypochlorhydria (low stomach acid)
• Pernicious anemia
• Medications (PPIs and other acid-suppressing drugs)
In general, the following patients are at risk for B12 deficiency:
• Vegetarians and vegans
• Aged 60 or over
• Regularly use PPIs
• Crohn’s disease, ulcerative colitis, celiac or IBS
B12 is the only vitamin that contains a trace element (cobalt), which is why it’s called coalmine.
Treatment of B12 deficiency
Cyanaocobalamin is the most frequently used form of B12 supplementation in the US. But recent evidence suggests that methylcobalamin is superior to cyanocobalamin especially in neurologic and psychiatric illness. Methylcobalamin is better absorbed because it bypasses several potential problems in the B12 absorption cycle. In conclusion, if the diagnosis of B12 deficiency is suspected on the basis of clinical findings, supplementation treatment should be administered even if the assayed level of the vitamin is not low.