Background Information—Form and Function of B12
Vitamin B12 Form
Cyanocobalamin has no known biochemical function. It must be converted to become active. It gets converted for use into hydroxocobalamin, methylcobalamin, or adenosylcobalamin. These three forms are equal in bioavailability.An exception to this is for the use of adenosylcobalamin in infants with a rare inborn error of synthesis.Methylcobalamin and adenosylcobalamin are coenzyme forms of B12.Hydroxocobalamin can be converted into the above two forms.
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Vitamin B12 is used for DNA synthesis, homocysteine metabolism, S-adenosylmethionine, red blood cell formation, nervous system and immune system function.Vitamin B 12 is necessary for folate to be metabolized properly into Methionine and Succinyl-CoA. Low levels of B12 and increased levels of folate are associated with higher concentrations of methylmalonic acid (MMA) and total plasma homocysteine (HCY).
Vitamin B12 Sources
The average American diet contains adequate amounts of vitamins B12, ranging from 5-15 mcg/day. Meat, poultry, fish, eggs, and dairy, constitute the primary food sources. It is not found in most non-animal food sources. Individuals consuming a plant-based diet are at an increased risk of deficiency. Non-meat food sources such as chlorella, spirulina, nori, and fermented soy contain mostly B12 analogues which have no activity in humans. Fifty-one percent of those following a macrobiotic diet were found to be deficient.Vegan Diets 0.3-0.4 mcg/dayLacto-vegetarians 1.4 mcg/day
Recommended Dietary Allowances (RDA)Males >14 years: 2.4 mcg/dayFemales >14 years: 2.4 mcg/dayPregnancy: 2.6 mcgLactation: 2.8 mcg
Absorption of B12
Pepsin and hydrochloric acid (HCL) are necessary for cleaving B12 from protein in stomach.Individuals with low levels are at a greater risk of deficiency due to decreased break down for absorption.B12 supplements (crystalline B12) do not require HCL or pepsin to bind to intrinsic factor (IF).B12 supplements are absorbed normally in hypochlorhydria.Intrinsic factor (IF) is made in the stomach and necessary for carrying B12 from the stomach to intestines for absorption.Individuals with genetic SNPs impairing intrinsic factor (IF) production are also at a greater risk of deficiency and must rely on B12 injections, bypassing the need for IF.IF becomes fully saturated at 2 mcg of B12.Large doses can be absorbed through passive diffusion which doesn’t require IF. This accounts for 1-2% of absorption.1000 mcg/day can overcome loss of IF due to pernicious anemia.Pernicious anemia is an autoimmune disease characterized by the destruction of parietal cells which produce IF.
Possible Causes of Vitamin B12 Deficiency
Pernicious anemia—Auto antibodies against parietal cells and IFGastric disease or surgeryChronic atrophic gastritis—parietal cell death/autoimmuneUse of gastric acid inhibitors (antacids, histamine receptor 2 antagonists, proton pump inhibitors)Pancreatic disease or pancreatectomyOther intestinal diseases: parasitic infections, bacterial overgrowth, ileal resection, impaired B12/IF absorption.Medications, such as cholestyramine and metformin, that impair B12 absorption or metabolism.Limited/poor food sources/choices that result in general malnutrition. Examples include vegan or vegetarian diet.Chronic alcoholismInherited disorders involved in B12 trafficking and metabolismMiscellaneous: including HIV and nitrous oxide anesthesiaConditions that result in chronic diarrhea or malabsorption states, such as celiac disease and Crohn’s disease.Helicobacter pylori infection results in hypochlorhydria. Eradicating H Pylori can improve B12 levels.Long term psyllium supplementation (> 1 year)Genetic factors can affect absorption and transport. Individuals with genetically higher methylmalonic acid levels will require higher-than-normal B12 dose...