Vitamin B12 (Cobalamin) Functions
Vitamin B12 is a water soluble vitamin, an essential nutrient needed for :
- Synthesis of DNA and thus production of the red blood cells and other cells
- Synthesis of the amino acid methionine from homocysteine thus preventing high blood homocysteine levels
- Synthesis of proteins and fats
- Proper functioning of the nerves
The chemical name for vitamin B12 is cobalamin, because it contains cobalt.
Recommended Daily Intake
The Recommended Dietary Allowance (RDA) for vitamin B12 for adults is 2.4 mcg/day, during pregnancy 2.6 mcg/day and during lactation 2.8 mcg/day . *Mcg = microgram = 1/1000 mg.
Foods High in Vitamin B12
- Vitamin B12 in significant amounts is naturally present only in animal foods; it is not produced by animals but by bacteria living in their guts . Cooking can decrease the vitamin B12 content of foods by up to 45% and reheating by another 45% .
- Human breast milk and infant formula contain enough vitamin B12 to meet the needs of infants 0-12 months of age [1,2].
- Normal bacteria in the human gut can produce some vitamin B12, but it is not known, if it can be absorbed .
Good Sources of Vitamin B12 for Vegans
- Vitamin B12 fortified ready-to-eat cereals and other plant foods and beverages
- Nutritional yeast powder or flakes
A freshwater green algae chlorella and spirulina, a seaweed (red algae) nori and other seaweeds: akaba-gin-nansou, arame, asakusanori (Porphyra tenera), dulse (Palmaria palmata), hijiki, kelp, kombu, maruba-amanori (Porphyra suborbiculata), wakame and fermented plant foods (kimchi, miso, tempeh, tofu, soy sauce, baker’s or brewer’s yeast, yeast extract spread, barley malt syrup, Japanese fermented black tea) alone do not provide sufficient amount of vitamin B12 [23,24,25,26].
Ovo-lacto vegetarians can obtain some vitamin B12 from eggs and dairy products but they may still need to eat fortified foods or take supplements .
Chart 1. Examples of Foods High in Vitamin B12
Vitamin B12 (mcg)
|Shellfish: clams (3 oz, 85 g)
|Liver: beef, veal, lamb (3 oz, 85 g)
|Octopus (3 oz, 85 g)
|Shellfish: oysters, mussels, whelks (3 oz, 85 g)
|Organ meats (liver, heart, kidney, spleen, brain) (3 oz, 85 g)
|Fish: herring, mackerel, sardines, tuna, trout, bass, bluefish, salmon (3 oz, 85 g)
|Crabs (3 oz, 85 g)
|Game meat: caribou, deer, emu, moose, rabbit (3 oz, 85 g)
|Red meat: beef, lamb, veal (3 oz, 85 g)
|Ostrich (3 oz, 85 g)
|Cheese (2 oz, 57 g)
|Turkey (3 oz, 85 g)
|Goose liver pate ( 1 tbsp, 13 g)
|Milk, cow’s (1 cup, 237 mL)
|Eggnog (1 cup, 237 mL)
|Yogurt (6 oz, 170 mL)
|Pork (3 oz, 85 g)
|Egg, hen (50 g)
|Ice cream (1/2 cup, 90 g)
|Chicken, duck, goose (3 oz, 85 g)
FORTIFIED PLANT FOODS
|Energy and sport drinks (8 oz, 237 mL)
|Almond milk (1 cup, 237 mL)
|Formulated bar (1.7 oz, 48 g)
|Meatless meat substitutes (3 oz, 85 g)
|Margarine-like spread (1 tbsp, 14 g)
|Soy milk (8 oz, 237 mL)
|Infant formula, prepared (100 mL)
|Nutritional yeast (Saccharomyces cerevisiae) flakes (2 full tsp)
Vitamin B12 Absorption, Bioavailability and Stores
Vitamin B12 is absorbed in the last part of the small intestine (terminal ileum). In order to be absorbed, it must be first separated from the food proteins (with the help of the pancreatic enzymes and gastric acid) and then combined with intrinsic factor (IF) produced in the stomach. Sufficient absorption can occur only in the presence of calcium provided by the pancreas. This means that disorders of the stomach, pancreas and the last part of the small intestine can affect vitamin B12 absorption.
Vitamin B12 from meat is absorbed better than from eggs . Vitamin B12 in fortified foods is not bound to proteins, so it is absorbed better than the vitamin naturally occurring in foods [*].
The amount of vitamin B12 that is absorbed increases with the dose, but the percentage of the vitamin that is absorbed decreases. For example, about 50% of the vitamin is absorbed from a 1 mcg dose, 20% from a 5 mcg dose, 5% from a 25 mcg dose and 1% from a 1,000 mcg dose .
More than 2.5 mg (2,500 mcg) of vitamin B12–1,000 times as much as the daily requirement–can be stored in the human body. This is why vitamin B12 deficiency usually develops only after 3-5 years after complete cessation of the vitamin intake .
Interactions with Drugs
The following drugs may decrease the absorption of vitamin B12: antiepileptic drugs, chloramphenicol, cholestyramine, colchicine, proton pump inhibitors (omeprazole, lansoprazol), metformin and nitrous oxide but more research is warranted [1,15,42].
Interactions with Foods
There are no known foods or nutrient supplements that would either inhibit or stimulate vitamin B12 absorption.
Normal Blood Levels
According to Mayo Medical Laboratories, normal blood values are 180-914 ng/L; levels 150-400 ng/L are considered borderline low . Normal reference ranges for blood vitamin B12 levels differ among laboratories.
Vitamin B12 Deficiency: Causes, Symptoms
- Food-bound vitamin B12 malabsorption
- Certain stomach conditions, such as atrophic gastritis caused by Helicobacter pylori infection, partial surgical removal of the stomach [4,5], gastric bypass (bariatric surgery) in treatment of obesity [4,6] and sarcoidosis  are associated with reduced secretion of gastric acid, which is required for the separation of vitamin B12 from the food proteins, so they can affect vitamin B12 absorption from foods, but not the absorption of free vitamin B12 from supplements .
- Chronic pancreatitis, usually in chronic alcoholics, may result in insufficient secretion of a pancreatic enzyme that separates vitamin B12 from the proteins in the food.
- Insufficient secretion of intrinsic factor from the gastric mucosal layer (the factor is required for vitamin B12 absorption) [1,8]:
- Autoimmune atrophic gastritis resulting in pernicious anemia (mainly in people after 60); it may run in families
- Infection by H. pylori bacteria
- Congenital pernicious anemia
- In the small intestinal bacterial overgrowth (SIBO), bacteria may consume dietary vitamin B12 
- Fish tapeworm in the small intestine may consume dietary vitamin B12 .
- Celiac disease, Crohn’s disease, tropical sprue, intestinal lymphoma, HIV/AIDS or surgery, including weight loss surgery , may affect the end part of the small intestine (terminal ileum), which is the main site of vitamin B12 absorption.
- No vitamin B12 intake in strict vegetarian (vegan) diet [8,27] or due to meat and milk avoidance after gastric bypass surgery . Because of the significant body stores of vitamin B12, it may take 3-5 years for deficiency to develop after starting a vegan diet.
- Vitamin B12 loss during pregnancy or breastfeeding, which can also cause vitamin deficiency in a child, especially if the mother is a vegan
- Severe folate deficiency
- Rare inborn disorders of vitamin B12 metabolism (cobalamin C, D, E an F disease) 
- Burning, reddened tongue (especially at the edges), loss of appetite, constipation, weight loss
- Early satiety and abdominal bloating due to stomach inflammation
- Lemon-yellow, waxy pallor, abnormal, patchy skin and hair pigmentations
- Increased heart rate
- Low-grade fever
- Neurological symptoms: paresthesia (numbness, tingling, burning) and pain in the feet and hands in the stockings and gloves pattern, weakness, unsteady gait (ataxia), loss of memory, irritability and impaired urination may develop even in the absence of anemia and may become permanent.
- Depression [15,16]
- If not treated, pernicious anemia is fatal.
- Reference: 
- Neural tube defects (anencephaly, spina bifida) in infants when their mothers were vitamin B12 deficient during pregnancy 
Diagnosis can be made by the following tests:
- Low blood vitamin B12 levels (<150 ng/L)
- High blood homocysteine levels
- High blood methylmalonic acid (MMA) levels
- Decreased number of red blood cells (low RBC) with enlarged erythrocytes (megaloblasts)
- Antibodies to intrinsic factor (in autoimmune atrophic gastritis)
- The blood folate levels have to be checked to exclude folate deficiency as a cause of megaloblastic anemia.
- For food bound vitamin B12 malabsorption: oral vitamin B12 supplements in small doses
- For pernicious anemia:
- Intramuscular injections (shots), 1 mg daily for 2 weeks, then weekly until blood tests normalize and then monthly for life.
- For some individuals (not in those with neurological disorders), oral doses 1,000-2,000 mcg/day can be appropriate, even if only about 1% (10 mcg from a 1,000 mcg dose) of vitamin B12 is absorbed in pernicious anemia [1,22,40].
- Potassium and iron supplements may be needed to prevent low blood potassium (hypokalemia) and iron levels caused by vitamin B12 supplements in high doses .
NOTE: Small amounts of animal food, for example after switching from vegan to ovo-laco vegetarian food, may not be enough to treat vitamin B12 deficiency .
Vitamin B12 Supplements
Without prescription (over-the-counter):
- Cyanocobalamin and methylocobalamin in the form of tablets, lozenges and capsules and as part of B-complex and multivitamin supplements are available. In order to be effective, in the human body, cyanocobalamin needs to be converted to methylcobalamin. Cyanocobalamin and methylcobalamin are considered to be equally effective .
- Sublingual tablets, powders or liquids (drops) do not appear to be more effective than regular tablets ; it is not clear if there is any benefit of chewable tablets over other oral forms .
- The effectiveness of vitamin B12 patches has not been sufficiently tested .
- Cyanocobalamin or hydroxocobalamin as a dermal (under the skin) and intramuscular injection are available. In one study, hydroxocobalamin increased blood vitamin B12 levels 4 times as much as cyanocobalamin . Individuals with chronic kidney disease should avoid cyanocobalamin supplements in large doses, since they often cannot efficiently metabolize cyanide .
- Nasal gel  and nasal spray (500 mcg once a week) [43,44] containing cyanocobalamin also appear to increase blood vitamin B12 levels.
Doses for Vegans
The recommended dose for vegans is 25-100 mcg/day, 1,000 mcg twice a week or 2,000 mcg once a week [25,30]. Vitamin B12 supplements are obtained from bacteria, not animals, so they are vegan, unless gelatin or other animal products are added to them .
Possible Vitamin B12 Supplements Benefits
Vitamin B12 supplements are EFFECTIVE for prevention and treatment of vitamin B12 deficiency, including autoimmune pernicious anemia [1,18].
Vitamin B12 in combination with vitamin B6 and folic acid is POSSIBLY EFFECTIVE in:
- Reducing high blood homocysteine levels. High blood homocysteine levels have been considered a risk factor for coronary heart disease (CHD), but lowering homocysteine with vitamin B12 or folate was not associated with decreased risk of CHD .
- Cyanide poisoning (intramuscular injection of hydroxocobalamin in high doses) [18,19]
Vitamin B12 supplements are POSSIBLY INEFFECTIVE or there is INSUFFICIENT EVIDENCE about their effectiveness in prevention or treatment of age-related macular degeneration (AMD) , aging, allergies, Alzheimer’s disease, asthma, cancer (breast, cervical, lung), canker sores, chronic fatigue syndrome (CFS), depression, diabetic neuropathy, eczema (atopic dermatitis), facial spasms, heart disease, hereditary pernicious anemia (Imerslund-Grasbeck disease ), high cholesterol and triglyceride levels, infertility in men, joint pain, kidney disease, liver disease, Lyme disease, multiple sclerosis, osteoporosis, psoriasis, re-blockage of blood vessels after heart artery dilation (balloon angioplasty), restless leg syndrome, ringing in the ears (tinnitus), sickle cell disease, sleep disorders, spina bifida in infants, stroke, vitiligo, or improving mood, energy or memory [15,18,19].
Who may benefit from vitamin B12 supplements?
Anyone at risk to develop vitamin B12 deficiency, including vegans, old people, breastfed infants, pregnant women, and some patients with thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, liver or kidney disease.
Vitamin B12 Safety: Side Effects, Toxicity
Toxicity from the overdose of vitamin B12 is not known . Side effects of vitamin B12 are rare and may include nausea, vomiting, mild diarrhea, blood clots, itching, acne rosacea and allergic reactions .
Reported harmful effects of vitamin B12 injections: anxiety, dizziness, headache, paresthesia (tingling), difficulty breathing, infection at the site of injection, gait abnormalities, arthritis, muscle pain, back pain, pulmonary edema, thrombosis, polycythemia vera .
Vitamin B12 in doses larger than Recommended Dietary Allowance (2.6 mcg/day) is pregnancy category C, which means no adverse effects in the fetuses were observed so far but insufficient studies have been done, so they cannot be ruled out .
Who should avoid vitamin B12 supplements?
- Individuals allergic to cobalt 
- Individuals with Leber’s disease–a hereditary eye disease in whom vitamin B12 supplements can cause serious damage of the optic nerve possibly resulting in blindness 
Causes of High Vitamin B12 Levels
- Excessive intake of vitamin B12 supplements
- Small Intestinal Bacterial Overgrowth (SIBO)
- Duodenal ulcer
- Liver disease: cirrhosis (mainly alcoholic), acute and chronic hepatitis, cancer, metastases
- Kidney disease (kidney failure) 
- Obesity, diabetes mellitus type 2 
- Cancer: breast, colon, stomach, pancreatic, multiple myeloma
- Malignant blood disorders: polycythemia vera, chronic myelocitic leukemia, primary hypereosinophilic syndrome, primary myelofibrosis, acute leukemia
- Therapy with high doses of vitamin A, vitamin C or estrogens 
- Other: bronchopulmonary disease, cardiovascular disease, gastrointestinal disease, autoimmune disease 
- Rarely: Gaucher disease, rheumatoid arthritis, systemic lupus erythematosus, defects of cyanide metabolism
- References: [35,36]
High vitamin B12 levels by themselves usually do not cause any symptoms .
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- List of foods with naturally occurring vitamin B12 US Department of Agriculture
- List of foods enriched with vitamin B12 US Department of Agriculture
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