Vitamin B12: Benefits, Dosage, and Safety

What vitamin b12 is

Vitamin B12 is a water-soluble vitamin naturally present in some foods, added to others, and available as a dietary supplement and a prescription medication. Because it contains the mineral cobalt, compounds with vitamin B12 activity are collectively called cobalamins. Methylcobalamin and 5-deoxyadenosylcobalamin are the metabolically active forms; hydroxycobalamin and cyanocobalamin become biologically active after conversion to these forms. It is bound to protein in food and must be released by stomach acid and then bound to intrinsic factor before it is absorbed in the distal ileum.

What it does

• Required for healthy red blood cell formation
• Required for the development, myelination, and function of the central nervous system
• Required for DNA synthesis
• Functions as a cofactor for methionine synthase, which converts homocysteine to the amino acid methionine (supporting formation of S-adenosylmethionine, a universal methyl donor)
• Functions as a cofactor for L-methylmalonyl-CoA mutase, which converts L-methylmalonyl-CoA to succinyl-CoA in the metabolism of propionate

How much vitamin b12 per day

These are population reference values from the NIH and the Dietary Reference Intakes. They are targets for healthy people, not personal prescriptions. The last column is the Tolerable Upper Intake Level, the most you should get from all sources combined.

Deficiency and who is at risk

Effects can include the hallmark megaloblastic anemia (large, abnormally nucleated red blood cells); low counts of white and red blood cells and platelets; glossitis (sore tongue); fatigue; palpitations; pale skin; weight loss; and infertility. Neurological changes such as numbness and tingling in the hands and feet, problems with balance, confusion, poor memory, and dementia can occur, and these neurological symptoms can appear without anemia. Because the body stores about 1 to 5 mg of vitamin B12 (roughly 1,000 to 2,000 times a typical daily intake), symptoms of deficiency can take several years to appear.

Who may need more

• Adults over 50, who are advised to get most of their B12 from fortified foods or supplements because they may not absorb food-bound B12 well
• People with pernicious anemia or atrophic gastritis
• People with celiac disease, Crohn's disease, or other malabsorption conditions
• People who have had gastric or intestinal surgery
• Vegetarians and vegans, and their breastfed infants
• People taking metformin or long-term gastric acid inhibitors

Food sources

Foods of animal origin: beef liver (70.7 mcg per 3 oz) and clams (17 mcg per 3 oz) are among the richest sources; also oysters, fish (salmon 2.6 mcg, canned light tuna 2.5 mcg per 3 oz), beef, poultry, eggs, milk (1.3 mcg per cup), yogurt, and cheese. Plant foods contain no vitamin B12 naturally, but fortified breakfast cereals and fortified nutritional yeasts (8.3 to 24 mcg per about 1/4 cup) provide highly bioavailable B12. Bioavailability is about three times higher from dairy than from meat, fish, and poultry.

Forms and absorption

Most common supplement form is cyanocobalamin; other forms are adenosylcobalamin, methylcobalamin, and hydroxycobalamin. No evidence indicates absorption rates differ by form. Absorption is about 50% at doses under 1 to 2 mcg (below the cobalamin-binding capacity of intrinsic factor) and drops sharply at higher doses (about 2% at 500 mcg, 1.3% at 1,000 mcg). Multivitamin/mineral supplements typically contain 5 to 25 mcg; B-complex supplements 50 to 500 mcg; B12-only supplements typically 500 to 1,000 mcg. Sublingual tablets and lozenges show no difference in efficacy versus oral. Prescription cyanocobalamin and hydroxycobalamin are given by intramuscular injection, and a prescription nasal gel is also available. Bioavailability from supplements is about 50% higher than from food.

Safety, excess and interactions

Too much

The Food and Nutrition Board did not establish a Tolerable Upper Intake Level for vitamin B12 because of its low potential for toxicity. Even at large doses, vitamin B12 is generally considered safe because the body does not store excess amounts, and it has not been shown to cause harm even at high doses. Absorption is self-limiting: only about 2% is absorbed at a 500 mcg dose and about 1.3% at a 1,000 mcg dose.

Interactions to know

• Gastric acid inhibitors - proton pump inhibitors such as omeprazole (Prilosec) and lansoprazole (Prevacid) can interfere with vitamin B12 absorption from food by slowing gastric acid release, and may lead to vitamin B12 deficiency
• Histamine H2-receptor antagonists such as cimetidine (Tagamet) and ranitidine (Zantac) can similarly interfere with vitamin B12 absorption from food
• Metformin - an antihyperglycemic used for prediabetes and diabetes, might reduce vitamin B12 absorption and significantly lower serum vitamin B12 concentrations

How status is measured

Status is typically assessed by serum or plasma vitamin B12 levels, with most laboratories defining subnormal values as below 200 or 250 pg/mL (148 or 185 pmol/L). Serum methylmalonic acid (MMA) is the most sensitive marker; a level greater than 0.271 micromol/L suggests deficiency, though MMA also rises with renal insufficiency and older age. Total plasma homocysteine rises as B12 status declines (a level above 15 micromol/L suggests deficiency) but has poor specificity. Experts suggest checking serum MMA when serum B12 is between 150 and 399 pg/mL (111 to 294 pmol/L) to help confirm a diagnosis.

Regulated by the FDA as a dietary supplement ingredient under DSHEA, not as a drug; supplements are not FDA-approved to diagnose, treat, cure, or prevent disease. The FDA Daily Value (DV) for vitamin B12 is 2.4 mcg for adults and children age 4 and older. Certain forms (injectable cyanocobalamin and hydroxycobalamin, and a nasal gel) are available as FDA-regulated prescription medications used to treat deficiency.

What the evidence supports

We grade the strength of evidence behind each common reason people take vitamin b12, mirroring how the NIH describes it.