Vitamin B12 - Absorption and Distribution

Absorption and Distribution

The human physiology of vitamin B₁₂ is complex, and therefore is prone to mishaps leading to vitamin B₁₂ deficiency. Protein-bound vitamin B₁₂ must be released from the proteins by the action of digestive proteases in both the stomach and small intestine. Gastric acid releases the vitamin from food particles; therefore antacid and acid-blocking medications (especially proton-pump inhibitors) may inhibit absorption of B₁₂. In addition some elderly people produce less stomach acid as they age thereby increasing their probability of B₁₂ deficiencies.

B₁₂ taken in a low-solubility, non-chewable supplement pill form may bypass the mouth and stomach and not mix with gastric acids, but these are not necessary for the absorption of free B₁₂ not bound to protein.

R-proteins (such as haptocorrins and cobalaphilin) are B₁₂ binding proteins that are produced in the salivary glands. They must wait until B₁₂ has been freed from proteins in food by pepsin in the stomach. B₁₂ then binds to the R-Proteins to avoid degradation of it in the acidic environment of the stomach.

This pattern of secretion of a binding protein secreted in a previous digestive step, is repeated once more before absorption. The next binding protein is intrinsic factor (IF), a protein synthesized by gastric parietal cells that is secreted in response to histamine, gastrin and pentagastrin, as well as the presence of food. In the duodenum, proteases digest R-proteins and release B₁₂, which then binds to IF, to form a complex (IF/B₁₂). B₁₂ must be attached to IF for it to be absorbed, as receptors on the enterocytes in the terminal ileum of the small bowel only recognize the B₁₂-IF complex; in addition, intrinsic factor protects the vitamin from catabolism by intestinal bacteria.

Absorption of food vitamin B₁₂ thus requires an intact and functioning stomach, exocrine pancreas, intrinsic factor, and small bowel. Problems with any one of these organs makes a vitamin B₁₂ deficiency possible. Individuals who lack intrinsic factor have a decreased ability to absorb B₁₂. In pernicious anemia, there is a lack of IF due to autoimmune atrophic gastritis, in which antibodies form against parietal cells. Antibodies may alternately form against and bind to IF, inhibiting it from carrying out its B₁₂ protective function. Due to the complexity of B₁₂ absorption, geriatric patients, many of whom are hypoacidic due to reduced parietal cell function, have an increased risk of B₁₂ deficiency. This results in 80–100% excretion of oral doses in the feces versus 30–60% excretion in feces as seen in individuals with adequate IF.

Once the IF/B₁₂ complex is recognized by specialized ileal receptors, it is transported into the portal circulation. The vitamin is then transferred to transcobalamin II (TC-II/B₁₂), which serves as the plasma transporter. Hereditary defects in production of the transcobalamins and their receptors may produce functional deficiencies in B₁₂ and infantile megaloblastic anemia, and abnormal B₁₂ related biochemistry, even in some cases with normal blood B₁₂ levels. For the vitamin to serve inside cells, the TC-II/B₁₂ complex must bind to a cell receptor, and be endocytosed. The transcobalamin-II is degraded within a lysosome, and free B₁₂ is finally released into the cytoplasm, where it may be transformed into the proper coenzyme, by certain cellular enzymes (see above).

It's important to note that investigations into the intestinal absorption of B₁₂ point out that the upper limit per single dose, under normal conditions, is about 1.5 µg: "Studies in normal persons indicated that about 1.5 µg is assimilated when a single dose varying from 5 to 50 µg is administered by mouth. In a similar study Swendseid et al. stated that the average maximum absorption was 1.6 µg "

The total amount of vitamin B₁₂ stored in body is about 2–5 mg in adults. Around 50% of this is stored in the liver. Approximately 0.1% of this is lost per day by secretions into the gut, as not all these secretions are reabsorbed. Bile is the main form of B₁₂ excretion; however, most of the B₁₂ secreted in the bile is recycled via enterohepatic circulation. Excess B12 beyond the blood's binding capacity is typically excreted in urine. Owing to the extremely efficient enterohepatic circulation of B₁₂, the liver can store several years’ worth of vitamin B₁₂; therefore, nutritional deficiency of this vitamin is rare. How fast B₁₂ levels change depends on the balance between how much B₁₂ is obtained from the diet, how much is secreted and how much is absorbed. B₁₂ deficiency may arise in a year if initial stores are low and genetic factors unfavourable, or may not appear for decades. In infants, B₁₂ deficiency can appear much more quickly.