Vitamin B12 - Food Sources and Bioavailability
Vitamin B12 is synthesised by certain bacteria in the gastrointestinal tract of animals and is then absorbed by the host animal. Vitamin B12 is concentrated in animal tissues, hence, vitamin B12 is found only in foods of animal origin. Foods that are high in vitamin B12 (µg/100g) include: liver (26–58), beef and lamb (1–3), chicken (trace-1), eggs (1–2.5) and dairy foods (0.3–2.4).
There are no naturally occurring bioactive forms of vitamin B12 from plant sources. Some plant foods contain added vitamin B12 and others e.g., seaweed and mushrooms contain vitamin B12 analogues that are inactive in humans, although 2 studies suggest certain types of Japanese seaweed (nori) have prevented vitamin B12 deficiency in vegans. Some foods that are contaminated or fermented by bacteria e.g., tempeh and Thai fish sauce, have been reported to contain vitamin B12, although these may have low affinity with IF and may be poorly absorbed.
A number of methods have been used to determine the vitamin B12 content of foods. Microbiological assays using vitamin B12 requiring bacteria were used, however, they are no longer the reference method as measurement uncertainty is high. Radio isotope dilution assays with labeled vitamin B12 and hog IF are used. Further advances are expected with the development of more specific monoclonal antibodies tests using specific binding proteins.
The bioavailability of vitamin B12 in humans is dependent on an individual’s gastrointestinal absorption capacity. As outlined previously, vitamin B12 absorption is complex and there are adverse changes with age. In view of the technical challenges and biological factors, there is little data on the bioavailability of dietary vitamin B12 in humans. It is thought that 1.5–2.0 µg of synthetic vitamin B12 saturates the IF-cobalamin ileal receptors, but other studies have shown higher absorption rates [1,11]. In normal humans the absorption of vitamin B12 from foods has been shown to vary depending on the quantity and type of protein consumed. Vitamin B12 from foods appear to have different absorption rates with better absorption from chicken and beef as compared to eggs.
Selected Food Sources of Vitamin B12 Food Micrograms (mcg)
per serving Percent DV* Clams, cooked, 3 ounces 84.1 3,504 Liver, beef, cooked, 3 ounces 70.7 2,946 Trout, rainbow, wild, cooked, 3 ounces 5.4 225 Salmon, sockeye, cooked, 3 ounces 4.8 200 Trout, rainbow, farmed, cooked, 3 ounces 3.5 146 Tuna fish, light, canned in water, 3 ounces 2.5 104 Nutritional yeasts, fortified with 100% of the DV for vitamin B12, 1 serving 2.4 100 Cheeseburger, double patty and bun, 1 sandwich 2.1 88 Haddock, cooked, 3 ounces 1.8 75 Beef, top sirloin, broiled, 3 ounces 1.4 58 Milk, low-fat, 1 cup 1.2 50 Yogurt, fruit, low-fat, 8 ounces 1.1 46 Cheese, Swiss, 1 ounce 0.9 38 Beef taco, 1 soft taco 0.9 38 Breakfast cereals, fortified with 25% of the DV for vitamin B12, 1 serving 0.6 25 Ham, cured, roasted, 3 ounces 0.6 25 Egg, whole, hard boiled, 1 large 0.6 25 Chicken, breast meat, roasted, 3 ounces 0.3 13
Vitamin B12 - Function
Selected Food Sources of Vitamin B12
| Food | Micrograms (mcg) per serving | Percent DV* |
|---|---|---|
| Clams, cooked, 3 ounces | 84.1 | 3,504 |
| Liver, beef, cooked, 3 ounces | 70.7 | 2,946 |
| Trout, rainbow, wild, cooked, 3 ounces | 5.4 | 225 |
| Salmon, sockeye, cooked, 3 ounces | 4.8 | 200 |
| Trout, rainbow, farmed, cooked, 3 ounces | 3.5 | 146 |
| Tuna fish, light, canned in water, 3 ounces | 2.5 | 104 |
| Nutritional yeasts, fortified with 100% of the DV for vitamin B12, 1 serving | 2.4 | 100 |
| Cheeseburger, double patty and bun, 1 sandwich | 2.1 | 88 |
| Haddock, cooked, 3 ounces | 1.8 | 75 |
| Beef, top sirloin, broiled, 3 ounces | 1.4 | 58 |
| Milk, low-fat, 1 cup | 1.2 | 50 |
| Yogurt, fruit, low-fat, 8 ounces | 1.1 | 46 |
| Cheese, Swiss, 1 ounce | 0.9 | 38 |
| Beef taco, 1 soft taco | 0.9 | 38 |
| Breakfast cereals, fortified with 25% of the DV for vitamin B12, 1 serving | 0.6 | 25 |
| Ham, cured, roasted, 3 ounces | 0.6 | 25 |
| Egg, whole, hard boiled, 1 large | 0.6 | 25 |
| Chicken, breast meat, roasted, 3 ounces | 0.3 | 13 |
Vitamin B12 also known as cobalamin, comprises a number of forms including cyano-, methyl-, deoxyadenosyl- and hydroxy-cobalamin. The cyano form, which is used in supplements, is found in trace amounts in food. The other forms of cobalamin can be converted to the methyl- or 5-deoxyadenosyl forms that are required as co factors for methionine synthase and L-methyl-malonyl-CoA mutase.
Methionine synthase is essential for the synthesis of purines and pyrimidines. The reaction depends on methyl cobalamin as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form methionine and tetrahydrofolate. A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anaemia. Folate deficiency independent of vitamin B12 also causes megaloblastic anaemia. Methylmalonyl CoA mutase converts methylmalonyl CoA to succinyl CoA, with 5-deoxy adenosyl cobalamin required as a cofactor. It is a defect in this reaction, and the subsequent accumulation of methylmalonyl CoA that is thought to be responsible for the neurological effects in vitamin B12 deficiency.
Serum vitamin B12 is bound to proteins known as transcobalamins (TC). The majority of the vitamin, approximately 80%, is transported on the inactive TCI (also called haptocorrin). The active transport protein for vitamin B12 is transcobalamin II (TCII), which caries about 20% of the vitamin in the circulation. Holo-transcobalamin (holo-TC) is TCII with attached cobalamin, which delivers vitamin B12 to cells. A low serum vitamin B12 concentration can be associated with a deficiency of TCI, while TCII levels and so vitamin B12 status remain adequate.
Vitamin B12 - Absorption
Vitamin B12 also known as cobalamin, comprises a number of forms including cyano-, methyl-, deoxyadenosyl- and hydroxy-cobalamin. The cyano form, which is used in supplements, is found in trace amounts in food. The other forms of cobalamin can be converted to the methyl- or 5-deoxyadenosyl forms that are required as co factors for methionine synthase and L-methyl-malonyl-CoA mutase.
Vitamin B12 is bound to protein in food and is available for absorption after it has been cleaved from protein by the hydrochloric acid produced by the gastric mucosa. The released cobalamin then attaches to R protein and passes into the duodenum where the R protein is removed and free cobalamin binds to Intrinsic Factor (IF). The IF-cobalamin complex is absorbed by the distal ileum and requires calcium. Vitamin B12 enters the circulation about 3–4 hours later bound to TC.
Vitamin B12 is secreted in bile and reabsorbed via the enterohepatic circulation by ileal receptors which require IF, thus the development of vitamin B12 deficiency is likely to be more rapid in patients with pernicious anaemia as IF is lacking. Vitamin B12 is excreted via the faeces, which is composed of unabsorbed biliary vitamin B12, gastrointestinal cells and secretions, and vitamin B12 synthesised by bacteria in the colon. It is estimated that daily vitamin B12 losses are in proportion to body stores with approximately 0.1% excreted per day. Excessive vitamin B12 in the circulation, e.g., such as after injections, usually exceeds the binding capacity of TC and is excreted in the urine.
Historically, vitamin B12 absorption has been measured by a number of methods including whole body counting of radiolabeled vitamin B12, metabolic balance studies or controlled feeding studies in vitamin B12-depleted individuals.
It is known that the total amount of vitamin B12 that is absorbed increases with vitamin B12 intake but that the percentage absorption decreases with increasing doses. One study using crystalline vitamin B12 supplements reported that 50% was retained at a 1 µg dose, 20% at a 5 µg dose and 5% at a 25 µg dose, suggesting saturation of the absorption mechanisms. The absorption capacity is thought to recover to baseline levels within 4-6 hours allowing for efficient absorption of the next dose. Approximately 1% of large doses of crystalline vitamin B12 found in some supplements (1,000µg), are absorbed through a mass action process, even in the absence of IF, indicating crystalline vitamin B12 in high doses and food vitamin B12 are absorbed by different mechanisms.
The Schilling test was the classical procedure for assessing the absorption of vitamin B12 but is now rarely used. As there has been no replacement a number of individual tests must be used to diagnose the cause of vitamin B12 deficiency. Tests that diagnose atrophic gastritis, a common cause of vitamin B12 malabsorption, include gastroscopy or serum gastrin and pepsinogen levels. Specific tests for pernicious anaemia include IF antibodies and serum gastrin estimation. MMA and tHcy are better markers of vitamin B12 status, although they are not appropriate for testing absorption. An overview of the medical management of vitamin B12 deficiency can be found in a recent article by Ralph Carmel.
Recommended Intakes
| Age | Male | Female | Pregnancy | Lactation |
|---|---|---|---|---|
| 0–6 months* | 0.4 mcg | 0.4 mcg | ||
| 7–12 months* | 0.5 mcg | 0.5 mcg | ||
| 1–3 years | 0.9 mcg | 0.9 mcg | ||
| 4–8 years | 1.2 mcg | 1.2 mcg | ||
| 9–13 years | 1.8 mcg | 1.8 mcg | ||
| 14+ years | 2.4 mcg | 2.4 mcg | 2.6 mcg | 2.8 mcg |
* Adequate Intake
Vitamin B12 Deficiency
Deficiency is usually caused by the malabsorption of vitamin B12 although dietary inadequacy is common in the elderly, vegans or ovo-lacto vegetarians with poor diets. Causes can also relate to inadequate IF production, atrophic gastritis, interference with the ileal uptake of vitamin B12 due to disease, resection or interference by bacterial overgrowth, drug-nutrient interactions as well as some less common genetic defects.
Vegans who consume no foods of animal origin can meet their vitamin B12 requirement from fortified foods or supplements. Ovo-lacto vegetarians with only a small intake of dairy foods or eggs, may require supplemental vitamin B12. Pregnant and/or lactating women following vegetarian or vegan diets are at high risk of deficiency due to the increased metabolic demand for vitamin B12 and require adequate intake of vitamin B12-containing foods or supplements.
The elderly are at risk of undernutrition in general, predominately due to reduced intake related to illness but also due to physical capacity e.g., difficulties with food preparation, and psychological factors e.g., depression. Protein bound malabsorption is thought to be the most common cause of sub-clinical vitamin B12 deficiency in the elderly and is commonly associated with some degree of atrophic gastritis. Gastritis or inflammation of the gastric mucosa increases with age and results in a reduction, or in some cases, complete loss of the acid required to cleave vitamin B12 from protein. Synthetic vitamin B12 remains available for absorption as it is not protein bound [3,22].
Pernicious anemia is the end stage of an auto-immune gastritis and results in the loss of synthesis of IF. It is this loss of IF that causes vitamin B12 deficiency and if untreated, megaloblastic anaemia and neurological complications develop. Pernicious anaemia is treated with vitamin B12 injections, or large doses of oral vitamin B12. Vitamin B12 deficiency will also develop after gastric antrum resection as this is the site of secretion of IF and acid.
Reduced ileal uptake of vitamin B12 can be caused by competition for vitamin B12 in patients with bacterial overgrowth or parasitic infection. Resection or diseases of the ileum such as Crohn’s Disease or other chronic bowel inflammatory conditions also cause malabsorption of vitamin B12.
The potential masking of vitamin B12 deficiency by folate fortification of the food supply has also raised some safety concerns. When vitamin B12 concentrations are low, high doses of folate (supplements or food fortification) allow DNA synthesis to continue, prevent megaloblastic anaemia and potentially “mask” vitamin B12 deficiency, potentially allowing homocysteine and MMA concentrations to rise and neurological damage to progress. Neurological damage in the absence of anaemia has been reported in 20-30% of cases of vitamin B12 deficiency. In view of this and the effect of vitamin B12 deficiency on pregnancy outcomes [26,27], there is discussion of the need to fortify flour with vitamin B12. Vitamin B12 fortification of flour is most likely to benefit those with poor dietary intake of vitamin B12 and the elderly with food bound malabsorption, but would be inadequate for those with pernicious anaemia, which affects 2–4% of the US population depending on ethnicity [28]. Patients with pernicious anaemia require larger oral supplements (e.g., 500–1,000 µg/d) or intramuscular injections. In developing countries, fortification could potentially have a more significant impact as the population’s intake is often low. However, as yet there not enough intervention trials on the effect of different fortification levels of flour in different populations.
Bibliography:
Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press, 1998.
Johnson MA. If high folic acid aggravates vitamin B12 deficiency what should be done about it? Nutr Rev 2007;65:451-8. [PubMed abstract]
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