Vitamin B12

Background Info:

  • A water-soluble vitamin
  • Naturally present in some foods, added to others, and available as a dietary supplement and a prescription medication
  • Exists in several forms and contains the mineral cobalt
    • Compounds with vitamin B12 activity are collectively called “cobalamins”
    • Methylcobalamin and 5-deoxyadenosylcobalamin are the forms of vitamin B12 that are active in human metabolism

Health Benefits: 

  • Required for proper red blood cell formation, neurological function, and DNA synthesis
  • Cardiovascular Disease
    • Elevated homocysteine levels have also been identified as an independent risk factor for cardiovascular disease
    • Elevated homocysteine levels are thought to promote thrombogenesis, impair endothelial vasomotor function, promote lipid peroxidation, and induce vascular smooth muscle proliferation
    • In the presence of insufficient vitamin B12, homocysteine levels can rise due to inadequate function of methionine synthase
  • Dementia and cognitive function
  • Energy and endurance
    • These claims are based on the fact that correcting the megaloblastic anemia caused by vitamin B12 deficiency should improve the associated symptoms of fatigue and weakness
    • Supplementation appears to have no beneficial effect on performance in the absence of a nutritional deficit

Biochemistry: 

  • Vitamin B12 functions as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase.
  • Methionine synthase catalyzes the conversion of homocysteine to methionine
    • Methionine is required for the formation of S-adenosylmethionine, a universal methyl donor for almost 100 different substrates, including DNA, RNA, hormones, proteins, and lipids.
  • L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate, an essential biochemical reaction in fat and protein metabolism.
    • Succinyl-CoA is also required for hemoglobin synthesis.

Recommended Dietary Allowance:

  • 0-6 months: 0.4 mcg
  • 7-12 months: 0.5 mcg
  • 1-3 years: 0.9 mcg
  • 4-8 years: 1.2 mcg
  • 9-13 years: 1.8 mcg
  • 14+ years: 2.4 mcg
  • Pregnant: 2.6 mcg
  • Lactating: 2.8 mcg

Sources:

Vitamin B12 is naturally found in animal products and is generally not present in plant foods

  • Beef: 1.4 mcg in 3 oz broiled top sirloin
  • Beef taco: 0.9 mcg in 1 soft taco
  • Cereals (fortified)
  • Cheese: 0.9 mcg in 1 oz Swiss
  • Cheeseburger: 2.1 mcg in double patty with bun
  • Chicken: 0.3 mcg in 3 oz roasted breast
  • Clams: 84.1 mcg in 3 oz
  • Egg: 0.6 mcg in 1 large hardboiled
  • Fish
  • Haddock: 1.8 mcg in 3 oz cooked
  • Ham: 0.6 mcg in 4 oz cured & roasted
  • Liver: 70.7 mcg in 3 oz cooked
  • Meat
  • Milk & milk products
  • Milk: 1.2 mcg in 1 cup low fat
  • Nutritional yeast products
  • Salmon: 4.8 mcg in 3 oz sockeye cooked
  • Trout: 3.5 mcg in 3 oz farmed & cooked
  • Trout: 5.4 mcg in 3 oz wild & cooked
  • Tuna: 2.5 mcg in 3 oz light canned
  • Yogurt:1.1 mcg in 8 oz of low fat fruit

Dietary supplements

  • Usually present as cyanocobalamin
    • A form that the body readily converts to the active forms methylcobalamin and 5-deoxyadenosylcobalamin
    • Dietary supplements can also contain methylcobalamin and other forms of vitamin B12
  • Existing evidence does not suggest any differences among forms with respect to absorption or bioavailability
    • However the body’s ability to absorb vitamin B12 from dietary supplements is largely limited by the capacity of intrinsic factor
    • For example, only about 10 mcg of a 500 mcg oral supplement is actually absorbed in healthy people
  • In addition to oral dietary supplements, vitamin B12 is available in sublingual preparations as tablets or lozenges
    • These preparations are frequently marketed as having superior bioavailability, although evidence suggests no difference in efficacy between oral and sublingual forms

Prescription medications

  • Vitamin B12, in the form of cyanocobalamin and occasionally hydroxocobalamin, can be administered parenterally as a prescription medication, usually by intramuscular injection
    • Parenteral administration is typically used to treat vitamin B12 deficiency caused by pernicious anemia and other conditions that result in vitamin B12 malabsorption and severe vitamin B12 deficiency
  • Vitamin B12 is also available as a prescription medication in a gel formulation applied intranasally, a product marketed as an alternative to vitamin B12 injections that some patients might prefer
    • This formulation appears to be effective in raising vitamin B12 blood levels, although it has not been thoroughly studied in clinical settings.

Digestion & Absorption:

  • Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach
    • 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
  • Free vitamin B12 then combines with intrinsic factor, a glycoprotein secreted by the stomach’s parietal cells, and the resulting complex undergoes absorption within the distal ileum by receptor-mediated endocytosis
  • Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed
    • Absorption decreases drastically when the capacity of intrinsic factor is exceeded (at 1–2 mcg of vitamin B12)

Deficiency: 

  • Pernicious anemia is an autoimmune disease that affects the gastric mucosa and results in gastric atrophy.
    • This leads to the destruction of parietal cells, achlorhydria, and failure to produce intrinsic factor, resulting in vitamin B12 malabsorption
    • If pernicious anemia is left untreated, it causes vitamin B12 deficiency, leading to megaloblastic anemia and neurological disorders, even in the presence of adequate dietary intake of vitamin B12
  • Vitamin B12 deficiency is characterized by megaloblastic anemia, fatigue, weakness, constipation, loss of appetite, and weight loss
  • Neurological changes, such as numbness and tingling in the hands and feet, can also occur
    • The neurological symptoms of vitamin B12 deficiency can occur without anemia, so early diagnosis and intervention is important to avoid irreversible damage
  • Additional symptoms of vitamin B12 deficiency include difficulty maintaining balance, depression, confusion, dementia, poor memory, and soreness of the mouth or tongue
  • During infancy, signs of a vitamin B12 deficiency include failure to thrive, movement disorders, developmental delays, and megaloblastic anemia
    • Many of these symptoms are general and can result from a variety of medical conditions other than vitamin B12 deficiency.
  • Large amounts of folic acid can mask the damaging effects of vitamin B12 deficiency by correcting the megaloblastic anemia caused by vitamin B12 deficiency without correcting the neurological damage that also occurs
    • Preliminary evidence suggests that high serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B12 deficiency
    • Permanent nerve damage can occur if vitamin B12 deficiency is not treated
    • For these reasons, folic acid intake from fortified food and supplements should not exceed 1,000 mcg daily in healthy adults

Deficiency Treatment:

  • Typically, vitamin B12 deficiency is treated with vitamin B12 injections, since this method bypasses potential barriers to absorption
    • However, high doses of oral vitamin B12 may also be effective
    • Overall, an individual patient’s ability to absorb vitamin B12 is the most important factor in determining whether vitamin B12 should be administered orally or via injection

Groups at Risk 

Older adults

  • Atrophic gastritis, a condition affecting 10%–30% of older adults, decreases secretion of hydrochloric acid in the stomach, resulting in decreased absorption of vitamin B12
  • Decreased hydrochloric acid levels might also increase the growth of normal intestinal bacteria that use vitamin B12, further reducing the amount of vitamin B12 available to the body
  • Individuals with atrophic gastritis are unable to absorb the vitamin B12 that is naturally present in food
    • Most, however, can absorb the synthetic vitamin B12 added to fortified foods and dietary supplements
    • As a result, the IOM recommends that adults older than 50 years obtain most of their vitamin B12 from vitamin supplements or fortified foods

Individuals with pernicious anemia

  • Pernicious anemia, a condition that affects 1%–2% of older adults, is characterized by a lack of intrinsic factor
  • Individuals with pernicious anemia cannot properly absorb vitamin B12 in the gastrointestinal tract
  •  Pernicious anemia is usually treated with intramuscular vitamin B12
    • However, approximately 1% of oral vitamin B12 can be absorbed passively in the absence of intrinsic factor, suggesting that high oral doses of vitamin B12 might also be an effective treatment.

Individuals with gastrointestinal disorders

  • Individuals with stomach and small intestine disorders, such as celiac disease and Crohn’s disease, may be unable to absorb enough vitamin B12 from food to maintain healthy body stores
  • Subtly reduced cognitive function resulting from early vitamin B12 deficiency might be the only initial symptom of these intestinal disorders, followed by megaloblastic anemia and dementia.

Individuals who have had gastrointestinal surgery

  • Surgical procedures in the gastrointestinal tract, such as weight loss surgery or surgery to remove all or part of the stomach, often result in a loss of cells that secrete hydrochloric acid and intrinsic factor
    • This reduces the amount of vitamin B12, particularly food-bound vitamin B12, that the body releases and absorbs.
  • Surgical removal of the distal ileum also can result in the inability to absorb vitamin B12
  • Individuals undergoing these surgical procedures should be monitored preoperatively and postoperatively for several nutrient deficiencies, including vitamin B12 deficiency

Vegetarians

  • Strict vegetarians and vegans are at greater risk than lacto-ovo vegetarians and nonvegetarians of developing vitamin B12 deficiency because natural food sources of vitamin B12 are limited to animal foods
  • Fortified breakfast cereals are one of the few sources of vitamin B12 from plants and can be used as a dietary source of vitamin B12 for strict vegetarians and vegans

Pregnant and lactating women who follow strict vegetarian diets and their infants

  • Vitamin B12 crosses the placenta during pregnancy and is present in breast milk
  • Exclusively breastfed infants of women who consume no animal products may have very limited reserves of vitamin B12 and can develop vitamin B12 deficiency within months of birth
  • Undetected and untreated vitamin B12 deficiency in infants can result in severe and permanent neurological damage.

Measuring Status:

  • Vitamin B12 status is typically assessed via serum or plasma vitamin B12 levels
  • Values below approximately 170–250 pg/mL (120–180 picomol/L) for adults indicate a vitamin B12 deficiency
    • However, evidence suggests that serum vitamin B12 concentrations might not accurately reflect intracellular concentrations
  • An elevated serum homocysteine level (values >13 micromol/L) might also suggest a vitamin B12 deficiency
    • However, this indicator has poor specificity because it is influenced by other factors, such as low vitamin B6 or folate levels
  • Elevated methylmalonic acid levels (values >0.4 micromol/L) might be a more reliable indicator of vitamin B12 status because they indicate a metabolic change that is highly specific to vitamin B12 deficiency

Upper Limit:

  • It has a low potential for toxicity

Interactions with Medications:

Chloramphenicol

  • Limited evidence from case reports indicates that chloramphenicol can interfere with the red blood cell response to supplemental vitamin B12 in some patients

Proton pump inhibitors

  • Proton pump inhibitors are used to treat gastroesophageal reflux disease and peptic ulcer disease. These drugs can interfere with vitamin B12 absorption from food by slowing the release of gastric acid into the stomach
    • However, the evidence is conflicting on whether proton pump inhibitor use affects vitamin B12 status
    • As a precaution, health care providers should monitor vitamin B12 status in patients taking proton pump inhibitors for prolonged periods

H2 receptor antagonists

  • Histamine H2 receptor antagonists, used to treat peptic ulcer disease
  • These medications can interfere with the absorption of vitamin B12 from food by slowing the release of hydrochloric acid into the stomach
  • Although H2 receptor antagonists have the potential to cause vitamin B12 deficiency, no evidence indicates that they promote vitamin B12 deficiency, even after long-term use
  • Clinically significant effects may be more likely in patients with inadequate vitamin B12 stores, especially those using H2 receptor antagonists continuously for more than 2 years

Metformin

  • Metformin, a hypoglycemic agent used to treat diabetes
  • Might reduce the absorption of vitamin B12, possibly through alterations in intestinal mobility, increased bacterial overgrowth, or alterations in the calcium-dependent uptake by ileal cells of the vitamin B12-intrinsic factor complex
  • Some studies suggest that supplemental calcium might help improve the vitamin B12 malabsorption caused by metformin, but not all researchers agree

References:

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