Diagnosis and treatment of B12 deficiency

I never directly measure serum Vitamin B12 levels anymore. Vitamin B12 (like C-Reactive Protein) acts as an acute phase reactant and therefore can be falsely elevated even in the presence of significant B12 deficiency. A much more sensitive test is the serum methylmalonic acid (or serum MMA for short). But remember that serum MMA is inversely proportional to the Vitamin B12 level. Therefore, a B12 deficiency would cause an elevated serum MMA. The reason is as follows:

Vitamin B12 acts as a co-factor in the conversion of methylmalonyl-CoA to succinyl CoA. Therefore a deficiency of B12 would cause a build up of methylmalonyl-CoA (and therefore serum MMA). Whatever! Just clinically remember that serum MMA is inversely related to B12. 

Now once we diagnose B12 deficiency, how do we treat B12 deficiency? For years, clinicians use to give Vitamin B12 shots. They were time consuming for the doctor and painful for the patients. Now we know that B12 can simply be replaced orally. But how? If a patient has pernicious anemia and is not making any intrinsic factor, how can oral B12 get from gut to blood? If we consider that the daily recommended daily allowance of B12 is 2 mcg and we typically prescribe 2000 mcg, the answer is probably related, at least partially, to simple diffusion.

I usually repeat another serum MMA about 2-3 months after starting treatment. Then I check it on a yearly bases if normal.