B12 Absorption Obstacles

There are a number of absorption obstacles in the B12 uptake pathway that can prevent the vitamin from being properly bound, transported, absorbed, and utilized. This illustration depicts several of these obstacles and summarizes the associated causes that interfere with normal B12 absorption.

stomach_normal_FINAL The first obstacle is a diet that is deficient in animal based foods. There is no active vitamin B12 in anything that grows out of the ground.[4] Thus, a vegan diet will contain no Cbl and require some form of Cbl supplementation. Vegetarians who may consume milk products can obtain Cbl from their diet, although in smaller amounts. The foods containing the highest amounts of Cbl are seafood, meats, and poultry, followed by eggs, milk, and other dairy sources.

A second common absorption obstacle that occurs is the inadequate secretion of acid and pepsin in the stomach, preventing the severing ofCbl from ingested animal protein. This disorder is called Food-Cobalamin Malabsorption (FCM) and it is the most prevalent form of B12 malabsorption.[10] In elderly patients, FCM can account for up to 60% of the cases of B12 deficiency.[10],[14] Any process that interferes with gastric acid production can lead to this impairment.[8],[9] Over the age of fifty, the body’s ability to generate sufficient hydrochloric acid (HCl) can decline significantly.[21] This condition is referred to as either hypochlorhydria (acid levels are merely reduced) or achlorhydria (hydrochloric acid is totally absent) and is commonly due to Atrophic gastritis. The incidence of hypochlorhydia in the elderly population is estimated to be 20-50%.[22]

The frequent and prolonged use of medications for gastric acid suppression such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RA’s) can also cause FCM.[10],[11]

A third obstacle that occurs is the inadequate secretion of IF from gastric parietal cells. Pernicious anemia, characterized by the loss or decline of IF secretion, is a classic cause of B12 deficiency and is also more prevalent among elderly patients. This condition is the end stage of type A chronic atrophic (autoimmune) gastritis. Type A gastritis results in the progressive destruction and eventual loss of parietal cells in the fundus and body of the stomach.[23] The loss of these parietal cells results in vitamin B12 deficiency and pernicious anemia.[23] Type A gastritis is assumed to be the forerunner of about 90% of the cases of pernicious anemia.[9] Gastrectomy and surgical resection of the terminal small intestine are also a cause of B12 malabsorption. Total gastrectomies and most partial gastrectomies eliminate both the only source of intrinsic factor and, especially, gastric acidity.[14]

A fourth absorption obstacle is the inadequate release of pancreatic enzymes to degrade the Cbl-R complex and release Cbl for binding to IF. Any interruption in the transfer of Cbl from R to IF can lead to Cbl malabsorption as the Cbl will be unable to bind to IF and be transported as a complex to the physiologic receptor cubilin.[17]

A fifth obstacle highlighted is the competition for Cbl uptake that can occur from bacteria or intestinal parasites, preventing Cbl from binding to IF for physiologic absorption. Once B12 has been taken up and utilized by bacteria, it is rendered unavailable for absorption.[24] Reduction in gastric acid from any cause may result in bacterial overgrowth in the stomach and a rise in the number of organisms as the intragastric pH rises.[25]

Other causes of bacterial overgrowth include reduced peristaltic activity and mucosal damage or atrophy. Autoimmune gastritis resulting from the production of parietal cell antibodies in pernicious anemia is the classical natural cause. The introduction of acid suppression drugs such as H2 antagonists and PPI’s also induce bacterial colonization of the stomach.[25] Finally, chronic infection with H Pylori resulting in gastric atrophy and loss of parietal cell mass is the most common cause of hypochlorhydria (low stomach acid) and/or achlorhydria (lack of stomach acid) worldwide.[25]