Adequate absorption of vitamin B12 requires adequate dietary intake, the presence of acid and pepsin
Pepsin is an enzyme that breaks down proteins into smaller peptides (that is, a protease). It is produced in the stomach and is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food.
A protease is an enzyme that catalyzes proteolysis, the breakdown of proteins into smaller polypeptides or single amino acids. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functio…
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Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed, but absorption decreases drastically when the capacity of intrinsic factor is exceeded (at 1–2 mcg of vitamin B12) [8]. Pernicious anemia is an autoimmune disease that affects the gastric mucosa and results in gastric atrophy.
Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach [5]. When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and, thus, does not require this separation step.
Introduction. Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach [ 5 ]. When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and, thus, does not require this separation step.
Stomach acid is needed to dissolve some B12 tablets, especially if not chewed. When taken in large enough doses, unbound B12 can overcome intrinsic factor defects because so much can be absorbed through passive diffusion.
Vitamin B12 status is typically assessed by measurements of serum or plasma vitamin B12 levels . The cutoff between normal vitamin B12 levels and deficiency varies by method and laboratory, but most laboratories define subnormal serum or plasma values as those lower than 200 or 250 pg/mL (148 or 185 pmol/L) [ 2 ]. Levels of serum methylmalonic acid (MMA), a vitamin B12-associated metabolite, are the most sensitive markers of vitamin B12 status, and an MMA level greater than 0.271 micromol/L suggests vitamin B12 deficiency [ 6-8 ]. However, MMA levels also rise with renal insufficiency and tend to be higher in older adults [ 6, 9, 10 ]. Another marker is total plasma homocysteine levels, which rise quickly as vitamin B12 status declines; a serum homocysteine level higher than 15 micromol/L, for example, suggests vitamin B12 deficiency [ 11 ]. However, this indicator has poor specificity because it is influenced by other factors, such as low folate levels and, especially, by declines in kidney function [ 6 ]. Experts suggest that if a patient’s serum vitamin B12 level is less than 150 pg/ml (111 pmol/L), the patient’s serum MMA levels should be checked to confirm a diagnosis of vitamin B12 deficiency [ 7, 9 ].
Vitamin B12 is bound to protein in food and must be released before it is absorbed [ 5 ]. The process starts in the mouth when food is mixed with saliva. The freed vitamin B12 then binds with haptocorrin, a cobalamin-binding protein in the saliva. More vitamin B12 is released from its food matrix by the activity of hydrochloric acid and gastric protease in the stomach, where it then binds to haptocorrin [ 1 ]. In the duodenum, digestive enzymes free the vitamin B12 from haptocorrin, and this freed vitamin B12 combines with intrinsic factor, a transport and delivery binding protein secreted by the stomach’s parietal cells. The resulting complex is absorbed in the distal ileum by receptor-mediated endocytosis [ 1, 5 ]. If vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and therefore does not require the separation step.
Multivitamin/mineral supplements typically contain vitamin B12 at doses ranging from 5 to 25 mcg [ 22 ]. Vitamin B12 levels are higher, generally 50–500 mcg, in supplements containing vitamin B12 with other B-complex vitamins and even higher, typically 500–1,000 mcg, in supplements containing only vitamin B12.
Parenteral administration is typically used to treat vitamin B12 deficiency caused by pernicious anemia as well as other conditions (e.g., tropical sprue, pancreatic insufficiency) that result in vitamin B12 malabsorption and severe vitamin B12 deficiency [ 5 ].
The average vitamin B12 level in the breast milk of women with vitamin B12 intakes above the RDA is 0.44 mcg/L [ 14 ]. The U.S. Food and Drug Administration specifies that infant formulas sold in the United States must provide at least 0.15 mcg vitamin B12 per 100 kcal [ 15 ].
The most common form of vitamin B12 in dietary supplements is cyanocobalamin [ 1, 3, 22, 23 ]. Other forms of vitamin B12 in supplements are adenosylcobalamin, methylcobalamin, and hydroxycobalamin [ 22 ]. No evidence indicates that absorption rates of vitamin B12 in supplements vary by form of the vitamin.
Vitamin B12 functions as a cofactor for two enzymes, methionine synthase and L-methylmalonyl-CoA mutase [ 1-3, 5 ] . Methionine synthase catalyzes the conversion of homocysteine to the essential amino acid methionine [ 1, 2 ].
In addition to the IF mechanism, passive diffusion normally accounts for 1-3% of B12 absorbed when obtained through normal food sources ( 3 ). Some inactive B12 analogues are most likely absorbed through passive diffusion.
While transcobalamin II transports B12 to cells, about 3/4 of the B12 in the blood is stored on haptocorrin (aka transcobalamin I and cobalophilin) ( 11, 12 ). Once the B12-TC2 complex arrives at the cell where it is needed, B12 is released from TC2 in the form of hydroxocobalamin.
Various studies have indicated that .1-.2% of the body’s B12 pool is lost per day; the .2% loss occurs in those with pernicious anemia ( 5) (see below for an explanation of pernicious anemia). The average nonvegetarian stores 2,000-3,000 µg B12 ( 5 ), while losing only about 3 µg/day ( 6 ). About 60% of the total amount of B12 in the body is stored in the liver and 30% is stored in the muscles ( 4 ).
The cobalamin-IF complex protects the cobalamin against bacterial and digestive enzyme degradation ( 4 ). The IF-receptor also ensures that cobalamins will be given priority for absorption over non-cobalamin corrinoids.
Digestion & Absorption of Protein-Bound B12. Microorganisms, primarily bacteria, are the only organisms known to manufacture B12. These bacteria are thought to live in water, soil, and the digestive tracts of animals. In animals, B12 is normally attached to a protein either for transport or storage. When humans eat animal foods, the B12 is ...
All 4 with sB12 in the 600-900 range fell to below 500 pg/ml in 2 months.
Transcobalamin II is made in the intestinal cells ( 7) where it picks up B12 and transports it to all body tissues through the blood and cerebrospinal fluid ( 1 ).