Absorption of vitamin B12 is a complex process, subject to problems at several points.
B12 from animal food enters the stomach as part of animal proteins and must first be liberated by pepsin and hydrochloric acid. Free B12 then attaches to R-protein, which is released from the salivary cells and parietal cells (the same cells that release hydrochloric acid). To be absorbed efficiently, B12 must attach to a protein called intrinsic factor (IF) which is also secreted in the stomach. This cannot happen until the R-protein complexes are broken down by pancreatic enzymes in the small intestine. B12 then binds with the intrinsic factor and proceeds through the gut to the lower portion of the small intestine, where the intrinsic factor-B12 complex attaches to cell receptors, a process that involves calcium.
Thus, deficiencies in pepsin, hydrochloric acid, R-protein, pancreatic enzymes, intrinsic factor, calcium and cell receptors can all lead to B12 deficiency through blocked absorption.
Once in the bloodstream, transport proteins bind to B12 and deliver it to the cells. Within the cells, enzymes liberate B12 from the protein complex and convert it to its two coenzyme forms, methylcobalamin and adenosylcobalamin. Deficiency in the required enzymes can block this conversion.
Because the absorption process is so complicated, and therefore subject to various blocks, many people--particularly the elderly--may develop deficiencies even though they are taking in plentiful B12 in their food. Fortunately, the body absorbs about 1-5 percent of free B12 by a process of passive diffusion. Thus supplementation with large doses of crystalline B12 or with foods extremely rich in B12 can successfully treat deficiencies caused by compromised protein digestion or lack of R-protein, intrinsic factor or pancreatic enzymes. Supplementation with the coenzyme forms methylcobalamin and adenosylcobalamin (the forms found in the cells) can overcome B12 deficiency in the cells caused by lack of, or malfunction of, conversion enzymes.