Vitamin B12 Absorption
Malabsorption is a common cause for vitamin B12 deficiency. The B12 absorption process is quite complex and can be disrupted in several places. In order to understand this better, it is worth considering how vitamin B12 works in our bodies and how malabsorption can affect this.
We consume B12 in our diets, the vitamin is found bound to animal proteins. Once in the stomach, the enzyme pepsin and gastric acid ensure that these proteins are digested and vitamin B12 released.
B12 then binds to endogenous transport proteins known as R-proteins which carry the B12 to the small intestine. Here, special pancreatic enzymes (predominantly trypsin) split the R-protein complex, releasing the vitamin B12, which then binds to the intrinsic factor (a different transport protein produced in the stomach).
Intrinsic Factor and Transcobalamin
Intrinsic factor attaches itself to specialized receptors located in the intestinal wall. At these sites the vitamin is able to be absorbed through the cell membranes – a process that requires the presence of calcium. Enzymes present in the cell endosome seperate the B12 from the intrinsic factor.
In the cells, the free vitamin B12 binds to a specific transport molecule called transcobalamin II (TC2), and is finally taken into the bloodstream. In the B12-TC2 some of the vitamin is transported around the body to various cells. Another portion binds to two other transcobalamins (TC1 and TC3) and travels to the liver to be stored.
Malabsorption: Conversion into Bioavailable B12 Forms
The B12-TC2 complex that is taken to body cells is converted into hydroxocobalamin inside the cell and is stored in the cell plasma in this form.
The vitamin B12 is converted into two bioactive forms. The second is methylcobalamin, which is required by cells and more specifically the cells making up the CNS, as methionine synthase is B12 dependent. On the other hand, the mitochondria, often described as the ‘engine room’ of the cell requires adenosylcobalamin, which is very important for a number of functions there.
Vitamin B12 Malabsorption
Now that the journey and development that vitamin B12 takes in the body is understood, it is possible to comprehend how different absorption problems may manifest.
A lack of hydrochloric acid and pepsin can prevent vitamin B12 from being extracted from food in the stomach and a lack of R protein can prevent vitamin B12 from being transported intact to the small intestine. These circumstances may arise from stomach lining disorders, insufficient production of R proteins and hydrochloric acid in saliva and from the gastric parietal cells.
Once the small intestine has been reached, pancreatic enzymes, intrinsic factor from the stomach and calcium from the diet are all required. At this stage, issues such as irritation of the intestinal mucosa, pancreatic disease, malnutrition and gastrointestinal diseases can result in absorption problems.
Some rare genetic blood disorders can lead to a lack of transcobalamin, which means the cells are provided with insufficient quantities of B12. If transcobalamin levels are sufficient, an excess of biologically inactive B12 analogs can prevent actual vitamin B12 from binding to transcobalamin and so despite good absorption a deficiency can develop. A build up of bacteria in the intestine can result in high levels of pseudo-B12, which is also caused by the consumption of algae.
Cells require specific enzymes to properly convert B12 into coenzyme form. In this step hereditary diseases (such as the aforementioned cobalamin disease) can cause serious problems and can prevent the necessary metabolic processes from taking place.
Possible Causes of Vitamin B12 Malabsorption
|Location||Nature of disorder||Causes|
|Stomach||intrinsic factor deficiency||chronic atrophic gastritis,|
|pepsin and acid deficieny||mild gastritis,|
use of certain medications
|Intestine||no absorption in the small intestine||diseases and irritations affecting the intestine,|
use of certain medications,
severe calcium deficiency
|Pancreas||missing pancreatic enzyme||exocrine pancreatic insufficiency, pancreatitis, pancreatic cancer, pancreatic cysts,|
ruptured pancreas and cystic fibrosis
|Blood and cells||improper application of vitamin B12||Hereditary diseases,|
use of certain medications,
Remedies for Malabsorption
The causes of absorption disorders are usually treatable, except in the case of hereditary cobalamin diseases and where parts of the digestive tract are missing. Due to the diversity of diseases that can affect absorption, there is great scope for treatment options. Dietary changes and regeneration of the intestinal flora are good initial approaches. Fungus and bacteria are sometimes a part of the problem.
Until the absorption problem is fixed, vitamin B12 should be administered in larger doses to compensate for the deficiency.
Vitamin B12 Supplements for Malabsorption
The entire absorption process that takes place in the stomach and intestine can be bypassed through the administration of high B12 doses. This is due to the fact that a small amount of the vitamin taken in will be absorbed via passive diffusion (approx. 1%) through the intestinal wall and enter the bloodstream. Issues resulting from a lack of pepsin, pancreatic enzymes and intrinsic factor can thereby be avoided. The same can be achieved through intramuscular injections. So far, the effectiveness of these methods has only been tested for hydroxocobalamin and cyanocobalamin. The result showed that hydroxocobalamin was better absorbed.1,2 There is a lack of evidence for methylcobalamin, but this too should be very effective.
With some genetic disorders cyanocobalamin appears to have no effect, whereas hydrxocobalamin has been shown to be effective in the treatment of such illnesses.3 Again, there are a lack of clinical studies investigating methylcobalamin and adenosylcobalamin, because these diseases are quite rare.
1Keith Boddy, et al. RETENTION OF CYANOCOBALAMIN, HYDROXOCOBALAMIN, AND COENZYME B12 AFTER PARENTERAL ADMINISTRATION The Lancet, Volume 292, Issue 7570, 28 September 1968, Pp.710–712
2Hertz, H., Kristensen, H. P. Ø. and Hoff-JØrgensen, E. (1964), Studies on Vitamin B12 Retention Comparison of Retention Following Intramuscular Injection of Cyanocobalamin and Hydroxocobalamin. Scandinavian Journal of Haematology, 1: 5–15. doi: 10.1111/j.1600-0609.1964.tb00001.x
3Hans C. Andersson, MD, Emmanuel Shapira, MD, PhD Biochemical and clinical response to hydroxocobalamin versus cyanocobalamin treatment in patients with methylmalonic acidemia and homocystinuria (cblC) The Journal of Pediatrics, Volume 132, Issue 1, January 1998, Pp.121–124