Vitamin B12 absorption

The consequence of bacterial bile acid metabolism [66, 74,77] is hardly clinically significant malabsorption [6] in otherwise healthy individuals [32,79], but in predisposed individuals this may be different. Accordingly, omeprazole interferes with the absorption of vitamin B12 [80-83] and protein assimilation [84], The mechanism for altered vitamin B12 absorption is prevention of its cleavage from dietary protein [83], for which the importance of the concurrent bacterial overgrowth has not yet been ruled out. 

Saltzman JR, Kemp JA, Golner BB, Pedrosa MC, Dallal GE, Russell RM Effect of hypo-chlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am CollNutr 1994 13 584-591. 

Oral vitamin B12 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin B12 absorption pathway is independent of intrinsic factor. Oral cobalamin is initiated at 1 to 2 mg daily for 1 to 2 weeks, followed by 1 mg daily. 

G9. Grasbeck, R., Kantero, I., and Srurala, M., Influence of calcium ions on vitamin B12 absorption in steatorrhea and pernicious anaemia. Lancet i, 234 (1959). 

G18. Grasbeck, R., Physiology and pathology of vitamin B12 absorption, distribution and excretion. Advances in Clin. Chem. 3, 299-366 (1960). 

Vitamin Bn deficiency Deficiency, although rare, results in two serious problems megaloblastic anaemia (which is identical to that caused by folate deficiency) and a specific neuropathy called Bi2-associated neuropathy or cobalamin-deficiency-associated neuropathy (previously called, subacute combined degeneration of the cord). A normal healthy adult can survive more than a decade without dietary vitamin B12 without any signs of deficiency since it is synthesised by microorganisms in the colon and then absorbed. However, pernicious anaemia develops fairly rapidly in patients who have a defective vitamin B12 absorption system due to a lack of intrinsic factor. It results in death in 3 days. Minot and Murphy discovered that giving patients liver, which contains the intrinsic factor, and which is lightly cooked to avoid denaturation, cured the anaemia. For this discovery they were awarded the Nobel Prize in Medicine in 1934. 

This vitamin is not made by plants or animals and can be synthesized only by a few species of microorganisms. It is required by healthy people in only minute amounts, about 3 p.g day. The severe disease pernicious anemia results from failure to absorb vitamin B12 efficiently from the intestine, where it is synthesized by intestinal bacteria or obtained from digestion of meat. Individuals with this disease do not produce sufficient amounts of intrinsic factor, a glycoprotein essential to vitamin B12 absorption. The pathology in pernicious anemia includes reduced production of erythrocytes, reduced levels of hemoglobin, and severe, progressive impairment of the central nervous system Administration of large doses of vitamin B12 alleviates these symptoms in at least some cases. ... 

Vitamin B12 can be absorbed when present in physiological amounts only if it is first bound to a specific protein—the so-called intrinsic factor—that tightly binds to the vitamin. The complex then passes through the jejunum to the ileum, which contains receptor sites for the vitamin B12/intrinsic factor complex. Calcium ions are required for the reaction between ileal receptors and the intrinsic factor/vitamin B12 complex. The reaction is inhibited by EDTA and reduced by a pH below 5.4. The vitamin appears to be separated from intrinsic factor at the ileal receptor sites and is then bound to another protein carrier, transcobalamin II, which transports the vitamin and permits its uptake by a number of tissues. The subject has been well reviewed by Jacob and her colleagues (Jl). Removal of 60 cm of ileum may impair vitamin B12 absorption and with the loss of 180 cm absorption is almost always affected. 

Examination of the bone marrow, although important, will only confirm that the hemopoiesis is megaloblastic. A deficiency of folic acid will also cause a megaloblastic anemia and it is not possible to identify the cause on the basis of morphology. A serum assay of both vitamins will usually indicate which is responsible. If the patient is vitamin B12 deficient, the next step is to carry out a vitamin B12 absorption test to confirm that the deficiency is due to a lack of intrinsic factor. Preferably this should not be done until the patient s vitamin B12 and hemoglobin levels have returned to normal, since the gastric and intestinal cells are also affected by a lack of vitamin B12 aborption may be less than optimal if it is attempted too early. Patients with pernicious anemia also have a histamine-fast achlorhydria and gastric atrophy. The disease appears to have an autoimmune basis and antibodies to intrinsic factor can be demonstrated in the serum of more than half of affected patients. 

Patients with severe atrophic gastritis may have impaired absorption of vitamin B12 and a reduced serum level of the vitamin, but this is not accompanied by either megaloblastic anemia or neuropathy. Parietal-cell antibodies have been found in 33% of patients with gastritis, none of these patients having pernicious anemia (12, V4). Intrinsic factor antibodies were not found, and this was not surprising since it is rare to find antibodies to intrinsic factor in the absence of pernicious anemia. Patients with superficial gastritis usually have normal vitamin B12 absorption and normal serum levels of the vitamin. 

Patients with exocrine pancreatic dysfunction may malabsorb vitamin B12 because a considerable part of the dietary vitamin may bind to R-proteins in the stomach. The R-proteins are normally broken down by pancreatic enzymes. The vitamin is released and binding to intrinsic factor then takes place. If the R-proteins are not degraded, then the vitamin B12 will remain bound to these proteins and will not be absorbed (M10). Harms and his colleagues (H27) measured vitamin B12 absorption in 19 children with exocrine pancreatic insufficiency and found the average absorption to be 8.0% compared to 59.2% in a control group. Adding pancreatin to the test dose of radiolabeled vitamin B12 increased absorption of the vitamin to an average of 61%. 

The Immerslund-Najman-Grasbeck syndrome is a term used to describe a congenital malabsorption of vitamin B12. It is perhaps the most common of the familial vitamin B12 absorption disorders and more than 100 cases have been described (C21). Although the majority of patients present during the first 2 years of life, a few have been seen much later. The disorder is charac-... 

D7. Doscherholmen, A., McMahon, J., and Ridley, D., Inhibitory effects of eggs on vitamin BI2 absorption Description of a simple ovalbumin Co-vitamin B12 absorption test. Br. ]. Haematol. 33, 261-272 (1976). 

F6. Fairbanks, V. F., Wahner, H. W., Valley, T. B., and Scheldt, R. M., Spurious results from dual-isotope (Dicopac) vitamin B12 absorption test due to rapid or variable rates of exchange of Co-B for 57Co-B12 bound to intrinsic factor. Nucl. Med. Commun. 4, 17-23 (1983). 

In the early stages of reduced vitamin B12 absorption, the amount of vitamin B12 bound to TCII decreases rapidly (10-21 days) without any decrease in the total serum B12 level. The total vitamin B12 concentration begins to decline only when the saturation of TCII falls below 5%. Reduced saturation of TCII is thus one of the earliest indicators of reduced intake of vitamin B12 and is detectable in advance of clinical disease. This makes holo-TCII particularly valuable for use as a screening test in susceptible populations. Elevated serum and urine concentrations of homocysteine and MMA occur somewhat later and represent early evidence of cellular dysfunction that occurs when body (liver) stores have been greatly depleted. 

Parietal cells also secrete intrinsic factor, which is necessary for the absorption of vitamin B12. Vitamin B12 is a cofactor of enzymes which synthesise tetrahydrofolic acid, which in turn is needed for the synthesis of DNA components. An impairment of DNA synthesis will affect rapidly dividing cell populations, among them the haematopoietic cells of the bone marrow, which may result in pernicious anaemia. This condition may result from a destruction of the gastric mucosa by, for example, autoimmune gastritis or the resection of large parts of the lower ileum, which is the main site of vitamin B12 absorption, or of the stomach. 

Very small amounts of vitamin B12 can be absorbed by diffusion across the intestinal mucosa. But, under normal conditions, this is insignificant, accounting for less than 1 % of large oral doses. The major route of vitamin B12 absorption is byway of attachment to a specific binding protein in the intestinal lumen. 

Circulating antibodies to hog intrinsic factor were also demonstrated in two pernicious anemia patients immunized with purified hog intrinsic factor concentrate (K5). Antibodies developed in their sera, which precipitated hog intrinsic factor in various immune reactions, immobilized it on electrophoresis, and depressed or abolished its enhancing effect upon vitamin B12 absorption in the intestine of other pernicious anemia patients. 

Physiology and Pathology of Vitamin B12 Absorption, Distribution, and Excretion Ralph Grasbeck... 

Force RW, Nahata MC. Effect of histamine H2-receptor antagonists on vitamin B12 absorption. Ann Pharmacother 1992 26(10) 1283-6. 

A number of assay methods for vitamin B]2 status, and for testing defects in the pathway of vitamin B12 absorption, are listed here ... 

Toxicity is unlikely following acute ingestions of even 100 times the recommended daily allowance. The most common manifestations of vitamin C toxicity are kidney stones, and in very rare circumstances, anemia (caused by interference with vitamin B12 absorption). 

Both direct and indirect (ftmctional) methods are available for assessing vitamin B status. The indirect tests include assays for urinary and serum concentrations of methylmalonic acid, plasma homocysteine, the deoxyuridine suppression test, and the vitamin B12 absorption test. Cyto-chemical staining of red blood cell (RBC) precursors and the test for IF blocking antibodies are also ancillary methods for assessing vitamin B12 status. 

The Schilling test is primarily a test of vitamin B12 absorption and not of status, but it permits differentiation of causes of vitamin B12 deficiency (pernicious anemia or intestinal malabsorption). The proportion absorbed from orally administered Co- or Co-labeled vitamin 6,2 is measured by determining the radioactivity in feces, urine, or serum or by externally scanning the liver. The usual procedure is to measure radioactivity in a 24-hour urine sample, which is collected after oral administration of 0.5 Xg of radioactive Co-labeled vitamin B12 after an overnight fast. In normal individuals, 8% or more of the dose administered is excreted in the urine, whereas in people with pernicious anemia, less than 7% (often 0% to 3%) is excreted. A confirmatory test for lack of IF requires mgestion of vitamin B,2 and IF. ... 

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