Vitamin B12 is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement and a prescription medication. Vitamin B12 exists in several forms and contains the mineral cobalt [1-4], so 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 .
Vitamin B12 is required for proper red blood cell formation, neurological function, and DNA synthesis [1-5]. Vitamin B12 functions as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase. Methionine synthase catalyzes the conversion of homocysteine to methionine [5,6]. 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 [3,5,6], an essential biochemical reaction in fat and protein metabolism. Succinyl-CoA is also required for hemoglobin synthesis.
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 [5,7]. 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) .
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 [3,5,9-11]. 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 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 [5-7,12].
Sources of Vitamin B12
Vitamin B12 is naturally found in animal products, including fish, meat, poultry, eggs, milk, and milk products. Vitamin B12 is generally not present in plant foods, but fortified breakfast cereals are a readily available source of vitamin B12 with high bioavailability for vegetarians [5,13-15]. Some nutritional yeast products also contain vitamin B12. Fortified foods vary in formulation, so it is important to read product labels to determine which added nutrients they contain.
Several food sources of vitamin B12 are listed in Table 2.
Table 2: Selected Food Sources of Vitamin B12 
|Clams, cooked, 3 ounces||84.1||1,402|
|Liver, beef, cooked, 3 ounces||70.7||1,178|
|Breakfast cereals, fortified with 100% of the DV for vitamin B12, 1 serving||6.0||100|
|Trout, rainbow, wild, cooked, 3 ounces||5.4||90|
|Salmon, sockeye, cooked, 3 ounces||4.8||80|
|Trout, rainbow, farmed, cooked, 3 ounces||3.5||58|
|Tuna fish, light, canned in water, 3 ounces||2.5||42|
|Cheeseburger, double patty and bun, 1 sandwich||2.1||35|
|Haddock, cooked, 3 ounces||1.8||30|
|Breakfast cereals, fortified with 25% of the DV for vitamin B12, 1 serving||1.5||25|
|Beef, top sirloin, broiled, 3 ounces||1.4||23|
|Milk, low-fat, 1 cup||1.2||18|
|Yogurt, fruit, low-fat, 8 ounces||1.1||18|
|Cheese, Swiss, 1 ounce||0.9||15|
|Beef taco, 1 soft taco||0.9||15|
|Ham, cured, roasted, 3 ounces||0.6||10|
|Egg, whole, hard boiled, 1 large||0.6||10|
|Chicken, breast meat, roasted, 3 ounces||0.3||5|
*DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers determine the level of various nutrients in a standard serving of food in relation to their approximate requirement for it. The DV for vitamin B12 is 6.0 mcg. However, the FDA does not require food labels to list vitamin B12 content unless a food has been fortified with this nutrient. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet. The U.S. Department of Agriculture’s (USDA’s) Nutrient Database Web site ) lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin B12 arranged by nutrient content and by food name.