Vitamin B12

Vitamin B12 is bound to protein in food and must be released before it is absorbed. 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. 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.

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, and that's why they more easily absorbed. Although there are claims that certain forms—like sublingual tablets or liquids placed under the tongue to be absorbed through the tissues of the mouth—have better absorption than traditional tablets, studies have not shown an important difference.

Recommended amount
1. Recommended intakeThe amount of vitamin B12 you need each day depends on your age. Average daily recommended amounts for different ages are listed below in micrograms (mcg).

- Birth to 6 months: 0.4 mcg
- Infants 7–12 months: 0.5 mcg
- Children 1–3 years: 0.9 mcg
- Children 4–8 years: 1.2 mcg
- Children 9–13 years: 1.8 mcg
- Teens 14–18 years: 2.4 mcg
- Adults: 2.4 mcg
- Pregnant teens and women: 2.6 mcg
- Breastfeeding teens and women: 2.8 mcg.

2. Upper Intake Level (UL)A Tolerable Upper Intake Level (UL) is the maximum daily dose unlikely to cause adverse side effects in the general population. No upper limit has been set for vitamin B12, as there is no established toxic level. However, some evidence suggests that supplements of 25 mcg per day or higher may increase the risk of bone fractures.

How harmful is if excess vitamin B12?
Even at large doses, vitamin B12 is generally considered to be safe because the body does not store excess amounts. Vitamin B12 is a water-soluble vitamin, so any unused amount will exit the body through the urine. Generally, up to 1000 mcg a day of an oral tablet to treat a deficiency is considered safe. The Institute of Medicine states “no adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals.” However, it is important not to start a high-dosage supplement of any kind without first checking with your doctor.

What happen if deficiency in vitamin B12?
Causes of vitamin B12 deficiency include difficulty absorbing vitamin B12 from food, lack of intrinsic factor (e.g., because of pernicious anemia), surgery in the gastrointestinal tract, prolonged use of certain medications (e.g., metformin or proton pump inhibitors, discussed in more detail below in the section on interactions with medications), and dietary deficiency. Because people who have difficulty absorbing vitamin B12 from food absorb free vitamin B12 normally, their vitamin B12 deficiency tends to be less severe than that of individuals with pernicious anemia, who cannot absorb either food-bound or free vitamin B12. Certain congenital conditions, such as hereditary intrinsic factor defects and congenital vitamin B12 malabsorption (Imerslund-Gräsbeck disease), can also cause severe vitamin B12 deficiency.

The effects of vitamin B12 deficiency can include the hallmark megaloblastic anemia (characterized by large, abnormally nucleated red blood cells) as well as low counts of white and red blood cells, platelets, or a combination; glossitis of the tongue; fatigue; palpitations; pale skin; dementia; weight loss; and infertility. Neurological changes, such as numbness and tingling in the hands and feet, can also occur. These neurological symptoms can occur without anemia, so early diagnosis and intervention is important to avoid irreversible damage. In addition, some studies have found associations between vitamin B12 deficiency or low vitamin B12 intakes and depression. In pregnant and breastfeeding women, vitamin B12 deficiency might cause neural tube defects, developmental delays, failure to thrive, and anemia in offspring.

Because the body stores about 1 to 5 mg vitamin B12 (or about 1,000 to 2,000 times as much as the amount typically consumed in a day), the symptoms of vitamin B12 deficiency can take several years to appear.

Vitamin B12 deficiency with the classic hematologic and neurologic signs and symptoms is uncommon. However, low or marginal vitamin B12 status (200–300 pg/mL [148–221 pmol/L]) without these symptoms is much more common, at up to 40% in Western populations, especially in those with low intakes of vitamin B12-rich foods. The prevalence of vitamin B12 deficiency varies by cutoff level and biomarker used. For example, among adults age 19 and older who participated in NHANES between 1999 and 2004, the rate of low vitamin B12 levels in serum was 3% with a cutoff of less than 200 pg/mL (148 pmol/L) and 26% with a cutoff of less than 350 pg/mL (258 pmol/L). Approximately 21% of adults older than 60 had abnormal levels of at least one vitamin B12 biomarker.

Typically, vitamin B12 deficiency is treated with vitamin B12 injections because this method bypasses any barriers to absorption. However, high doses of oral vitamin B12 might also be effective. A 2018 Cochrane Review included three randomized controlled trials (RCTs) that compared very high doses (1,000–2,000 mcg) of oral with intramuscular vitamin B12 for vitamin B12 deficiency in a total of 153 participants. The evidence from these studies, although of low quality, showed that the ability of high oral doses of vitamin B12 supplements to normalize serum vitamin B12 was similar to that of intramuscular vitamin B12.

Interactions with Medications
Vitamin B12 has the potential to interact with certain medications. In addition, several types of medications might adversely affect vitamin B12 levels. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin B12 status with their health care providers.

1. Gastric acid inhibitorsGastric acid inhibitors include proton pump inhibitors, such as omeprazole (Prilosec) and lansoprazole (Prevacid), and histamine 2-receptor antagonists, such as cimetidine (Tagamet) and ranitidine (Zantac). These drugs are used to treat gastroesophageal reflux disease and peptic ulcer disease. They can interfere with vitamin B12 absorption from food by slowing the release of gastric acid into the stomach and thereby lead to vitamin B12 deficiency.

2. MetforminMetformin, an antihyperglycemic agent used as first-line treatment for prediabetes and diabetes, might reduce the absorption of vitamin B12 and significantly reduce serum vitamin B12 concentrations.

Who is at risk of vitamin B12 deficiency?
The following groups are among those most likely to be vitamin B12 deficient.

1. Older adultsDepending on the definition used, between 3% and 43% of community-dwelling older adults, especially those with atrophic gastritis, have vitamin B12 deficiency based on serum vitamin B12 levels. The deficiency rate at a cutoff of less than 211 pg/mL (156 pmol/L) at admission to a long-term care facility, according to one study, was 14%, and 38% of these older adults had levels lower than 407 pg/mL (300 pmol/L).

Conditions associated with vitamin B12 inadequacy include pernicious anemia, present in about 15% to 25% of older adults with vitamin B12 deficiency. Atrophic gastritis, an autoimmune condition affecting 2% of the general population but 8%–9% of adults age 65 and older, decreases production of intrinsic factor and secretion of hydrochloric acid in the stomach and thus decreases absorption of vitamin B12. A third condition associated with vitamin B12 deficiency in older adults is Helicobacter pylori infection, possibly because this bacterium causes inflammation that leads to malabsorption of vitamin B12 from food.

2. Individuals with pernicious anemiaPernicious anemia is an irreversible autoimmune disease that affects the gastric mucosa and results in gastric atrophy. This disease leads to attacks on parietal cells in the stomach, resulting in failure to produce intrinsic factor and malabsorption of dietary vitamin B12, recycled biliary vitamin B12, and free vitamin B12. Therefore, without treatment, pernicious anemia causes vitamin B12 deficiency, even in the presence of adequate vitamin B12 intakes.

Pernicious anemia is the most common cause of clinically evident vitamin B12 deficiency around the world. The incidence of pernicious anemia in the United States is an estimated 151 per 100,000, and this condition is more common in women and in people of European ancestry.

3. Individuals with gastrointestinal disordersIndividuals 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. However, although rates of vitamin B12 deficiency are higher in people with celiac disease than other people, the evidence for whether rates of vitamin B12 deficiency are higher in people with Crohn’s disease is mixed. Vitamin B12 deficiency in people with Crohn’s disease is typically treated with intramuscular cobalamin injections, but high doses of oral cyanocobalamin therapy (e.g., 1,000 mcg/day) might be equally effective.

4. Individuals who have had gastrointestinal surgerySurgical procedures in the gastrointestinal tract, such as for weight loss or to remove all or part of the stomach, can cause a complete or partial loss of cells that secrete hydrochloric acid and cells that secrete intrinsic factor. Thus, these procedures reduce the amount of vitamin B12, particularly food-bound vitamin B12, that the body absorbs. High doses (1,000 mcg/day) of oral methylcobalamin supplements appear to be as effective as hydroxycobalamin injections in normalizing vitamin B12 values in patients who have undergone Roux-en-Y gastric bypass surgery.

5. VegetariansVegans who consume no animal products and vegetarians who consume some animal products (e.g., dairy products, eggs, or both) but not meat have a higher risk of developing vitamin B12 deficiency because natural food sources of vitamin B12 are limited to animal foods. Consumption of foods fortified with vitamin B12 (such as fortified nutritional yeasts) as well as vitamin B12 supplements can substantially reduce the risk of deficiency.

6. Infants of vegan womenExclusively breastfed infants of women who consume no animal products might have very limited reserves of vitamin B12 and can develop vitamin B12 deficiency, sometimes very early in life. The infant’s deficiency can be severe, especially if the mother’s deficiency is severe or caused by pernicious anemia; sometimes, the mother’s own deficiency is clinically mild and not recognized. Undetected and untreated vitamin B12 deficiency in infants can result in neurological damage, failure to thrive, developmental delays, and anemia. The reasons include the small amounts of vitamin B12 in the breast milk of vegan mothers as well as the limited amounts of vitamin B12 crossing the placenta in these women during fetal development.

Vitamin B12 and Health
1. CancerThe evidence for a relationship between vitamin B12 and cancer risk is mixed. Some evidence supports a link between increased cancer risk and higher intakes or blood concentrations of vitamin B12, some supports a link with lower intakes or concentrations, and some evidence indicates no link at all.

Observational evidence supporting an association between higher vitamin B12 levels and increased cancer risk includes an analysis of data on 757,185 people (median age 56 years) with plasma vitamin B12 measurements. The results showed that the adjusted 1 year risk of cancer was 1.74 to 4.72 times higher among those with vitamin B12 levels above 813 pg/mL (600 pmol/L) than those with levels in the normal range of 203–813 pg/mL (150–600 pmol/L). An analysis by some of the same investigators of data from Danish medical registries for 25,017 people who had a cancer diagnosis between 1998 and 2014 found 1-year survival rates of 35.8% in those whose plasma cobalamin levels were higher than 1,084 pg/mL (800 pmol/L) and 69.3% in those with levels between 271 and 813 pg/mL (200–600 pmol/L).

Some observational evidence also shows an association between supplements containing vitamin B12 and a higher risk of certain types of cancer. For example, an assessment of 77,118 participants age 50 to 76 years in the Vitamins and Lifestyle cohort study found that use of at least 55 mcg/day supplemental vitamin B12 for an average of 10 years was associated with a 40% higher risk of lung cancer in men. However, the study found no association between supplemental vitamin B12 use and cancer risk in women.

Limited clinical trial evidence supports the finding that higher vitamin B12 intakes might increase cancer risk. In an analysis of data on 2,524 participants in the B Vitamins for the Prevention of Osteoporotic Fractures trial who were treated with supplements containing 400 mcg/day folic acid and 500 mcg/day vitamin B12 for 2 to 3 years, the risk of colorectal cancer was significantly higher, at 3.4%, in the supplementation group than in the placebo group, whose rate was 2% . However, high folic acid levels are potentially linked to increased risk of colorectal cancer, so the result might be due to the folic acid rather than the vitamin B12. Furthermore, the supplements had no significant effect on overall cancer risk.

Some observational evidence shows no association between high vitamin B12 concentrations or intakes and increased risk of certain cancers. For example, higher vitamin B12 intakes or serum concentrations were not associated with an increased risk of pancreatic cancer, breast cancer, or esophageal cancer or gastric cancer. Clinical trials support the lack of association between higher vitamin B12 intakes and cancer risk. For example, a meta-analysis of 18 RCTs that included 74,498 individuals found that supplements containing B vitamins, including 20 to 2,000 mcg/day vitamin B12, had little or no effect on cancer incidence, cancer deaths, or all-cause mortality during follow-up periods of 2 to 7.3 years.

Finally, evidence pointing to an association between lower vitamin B12 levels and a higher cancer risk includes observational data showing a risk of gastric cancer that was 5.8 times higher in male smokers with lower vitamin B12 levels (less than 394 pg/mL [291 pmol/L]) than in those with levels higher than 591 pg/mL (436 pmol/L). Also, two meta-analyses found associations between lower vitamin B12 concentrations or intakes and a higher risk of colorectal cancer and prostate cancer. More evidence is needed to clarify whether high or low intakes of vitamin B12 influence the risk of cancer as well as the role of vitamin B12 in preventing cancer.

2. Cardiovascular disease and strokeVitamin B12 is involved in the breakdown of a protein called homocysteine. High homocysteine levels are associated with an increased risk of heart disease and stroke as it may promote the formation of blood clots and excess free radical cells, and may impair normal blood vessel function. A lack of adequate vitamin B12 can increase homocysteine levels.

Although epidemiological studies have found that vitamin B12 supplementation can decrease homocysteine levels, they have not consistently shown a decreased risk of cardiovascular events in taking the vitamin. Therefore the American Heart Association does not advocate for the routine use of B vitamin supplements in reducing cardiovascular disease risk. However, vitamin B12 supplements can be important for some individuals with genetic variants that lead to high homocysteine levels.

3. Cognitive functionHigh homocysteine levels are linked with a higher incidence of Alzheimer’s disease, dementia, and cognitive decline. Similar to cardiovascular disease, although the research has shown that vitamin B12 supplementation reduces homocysteine blood levels, this has not translated into reduced rates of cognitive decline. A Cochrane review on folic acid supplements and cognition, with or without vitamin B12, did not find a significant effect of the supplements vs. placebo on cognitive function in healthy elderly people or people with dementia. Another review of 14 randomized controlled trials also did not consistent evidence of benefit with the use of vitamin B12 supplements, alone or with other B vitamin supplements, on cognitive function in people with either normal or impaired cognition. These findings do not preclude a possible benefit among some individuals with low vitamin B12 levels, and more research is needed.

4. Energy and enduranceBecause of its role in energy metabolism, vitamin B12 is often promoted as an energy enhancer and an athletic performance and endurance booster. However, vitamin B12 supplementation appears to have no beneficial effect on performance in the absence of a nutritional deficit.

Food Sources
Vitamin B12 is found in a wide variety of animal foods. Plant foods have no vitamin B12 unless they are fortified. You can get recommended amounts of vitamin B12 by eating a variety of foods including the following:

- Fish, meat, poultry, eggs, milk, and other dairy products contain vitamin B12.
- Clams, oysters, and beef liver are some of the best sources of vitamin B12.
- Some breakfast cereals, nutritional yeasts, and other food products are fortified with vitamin B12.

To find out if a food has added vitamin B12, check the Nutrition Facts labelexternal link disclaimer. Manufacturers are not required to list vitamin B12 on the label if a food naturally contains this vitamin.

Did you know?
A B vitamin complex supplement is often touted to boost energy levels and mood. People who have a B vitamin deficiency may feel a rise in energy levels after using the supplement because the vitamin is directly involved in making healthy blood cells and can correct anemia if present. However, there is no evidence of benefit if people without a deficiency take extra B vitamins.

People who eat a vegan diet are often told to include Brewer’s or nutritional yeast for its B12 content. However, yeast does not naturally contain this vitamin and will only be present if fortified with it. Be aware that certain brands, but not all, contain B12.

Nori (purple laver), the dried edible seaweed used to make sushi rolls, is sometimes promoted as a plant source of vitamin B12. It does contain small amounts of active vitamin B12, but the amount varies among types of seaweed, with some containing none. Therefore is not considered a reliable food source.

Compiled and written by Crocus Media