Vitamin B12 (Cobalamin)

Vitamin B12 (cobalamin) is a water-soluble vitamin. The body needs it to make red blood cells and DNA, says the NIH (the US National Institutes of Health). B12 also helps build and keep the insulating coat of nerves. It contains the mineral cobalt, which is why compounds with B12 activity are called cobalamins. Adults need only 2.4 mcg (micrograms) a day, a few millionths of a gram.

Here is the part most people do not know: no plant and no animal makes vitamin B12. Only certain bacteria and archaea (single-celled microbes) do. Cows and sheep carry them in their stomachs. Plankton get B12 from bacteria and pass it on to fish larvae and shellfish.

So people get B12 mostly from ruminant meat and milk (from cud-chewing animals such as cows), fish and shellfish, according to a 2018 review. That is why plants do not make it. It also has the most complex structure of all vitamins, which Dorothy Hodgkin worked out in 1956, according to the Nobel Prize site.

Deficiency is more common than diet alone would suggest, because absorption has several steps and any of them can fail. In US survey data from 2007 to 2018, 3.6% of adults had a B12 below 200 pg/mL (picograms per milliliter of blood). And 12.5% were below 300 pg/mL. The body keeps a store of 2 to 3 mg, so a shortfall can take years to show.

Health benefits of vitamin B12

• ★★★B vitamins: no change in heart attacks, deathsIn 15 trials with 71,422 people, vitamin B6, folic acid or B12 (alone or combined) did not change heart attacks or deaths. B12 was mostly given with folic acid, so this is not a B12-only result, and strokes were slightly fewer (4.3% against 5.1%).
• ★★★Little or no benefit for thinkingIn 14 trials with 27,882 cognitively healthy people, mostly over 60, B vitamin pills probably did little or nothing for thinking. Among 879 people with mild memory problems (5 trials), there was no clear benefit either.
• ★★★Less B12 deficiency in children taking pillsIn 3 trials of 642 children under 12, B12 deficiency fell from 7.6% to 1.8% with B12 pills compared with placebo. Height, anemia and thinking skills showed little to no difference.
• ★★Pills raised B12 about as well as injectionsIn 3 trials of 153 people with B12 deficiency, 1,000 mcg a day by mouth gave levels not clearly different from injections. The evidence was low quality.
• ★★Long-term metformin lowered B12 levelsIn 390 people with type 2 diabetes taking insulin, metformin lowered B12 by 19% over 4.3 years. B12 deficiency at the end was 7.2 percentage points more likely.

Foods high in vitamin B12

B12 occurs naturally only in animal foods, and fish and shellfish lead our USDA ranking per serving. A 3 oz (85 g) serving of oysters has 13.6 mcg, 567% of the 2.4 mcg Daily Value (the FDA’s daily target for food labels). Herring follows with 11.6 mcg per 3 oz. Then come mackerel with 9.8 mcg per fillet (112 g) and sardines with 8.2 mcg per can (92 g).

Salmon, ground lamb and ground beef come next, then tuna and shrimp, as the ranking shows. Per 100 g, oysters have 16 mcg and herring 13.7 mcg.

Our ranking holds only 17 foods, so it leaves out some of the richest. The NIH table lists beef liver at 70.7 mcg per 3 oz and cooked clams at 17 mcg. A large egg has 0.5 mcg, plain fat-free yogurt 1.0 mcg per 6 oz container and cheddar 0.5 mcg per 1½ oz.

Absorption varies by food. The NIH says B12 seems about three times more available from dairy than from meat, fish and poultry. It also says supplements are absorbed about 50% better than food B12.

In a Norwegian survey of 5,937 people, plasma B12 rose with B12 from dairy and fish but not from meat or eggs. It plateaued at about 10 mcg a day. In the Framingham study, fortified cereal and dairy went with fewer low readings, and meat did not.

Cooking can cost some B12. In a study of round herring, grilling, boiling, frying, steaming and microwaving cut B12 by up to about 62%. Cooking in a vacuum-packed pouch did not. That is one fish in a lab, so treat the number as a hint.

Plants do not make B12. The NIH says fortified breakfast cereals and fortified nutritional yeast are readily available sources with high bioavailability (they are well absorbed). Nutritional yeast has 8.3 to 24 mcg per ¼ cup, so check the label. Dried purple laver (nori) is proposed as a plant source in one review.

For spirulina tablets, a bacterial test gave 6 to 9 times more B12 than a test based on intrinsic factor. Most of the intrinsic-factor-active compound (83%) was pseudovitamin B12, an inactive look-alike, rather than true B12. The one small study of chlorella had 17 people and no control group. The evidence for seaweed and algae is thin.

How vitamin B12 works

The biochemistry below is well established, but it comes from official reports and physiology studies, not from trials of B12 pills. Four ideas cover most of it.

B12 runs two enzymes, and absorption takes four steps and a special protein. The gut can take up only a little at a time, and the body keeps a store that it recycles. Then comes what has been seen in people.

It runs two enzymes

Two reactions in people need B12 as a coenzyme (an enzyme helper), according to EFSA (the EU’s food safety agency) and the NIH. In the cell fluid, methionine synthase turns homocysteine into the essential amino acid methionine, using a methyl group from folate. Methionine then forms S-adenosylmethionine, which hands methyl groups to almost 100 substances, among them DNA, RNA, proteins and fats.

In the mitochondria (the cell’s power plants), methylmalonyl-CoA mutase turns methylmalonyl-CoA into succinyl-CoA. This is part of breaking down propionate, a short-chain fat. When B12 runs short, homocysteine and methylmalonic acid build up.

That is why doctors measure them. The NIH says a methylmalonic acid above 0.271 µmol/L suggests B12 deficiency, and so does a homocysteine above 15 µmol/L. Homocysteine is also raised by low folate and poor kidney function, though.

The folate link is also why high folic acid intake worries some experts. A review notes concern about its possible harmful effects on nerves in people with an undetected B12 deficiency.

Absorption takes four steps and a special protein

B12 in food is bound to protein. Stomach acid and pepsin release it, and it first binds to haptocorrin, a protein in saliva. In the duodenum (the first part of the small intestine), enzymes free it from haptocorrin. It then binds to intrinsic factor, a protein made by cells of the stomach.

The complex is taken up in the last part of the small intestine through a receptor, then carried in the blood by transcobalamin. B12 added to fortified foods and supplements is already free, so it skips the first step, the NIH explains. This is why absorption fails in some people. Pernicious anemia is an autoimmune disease that destroys the cells making intrinsic factor.

Atrophic gastritis lowers stomach acid and intrinsic factor, which makes it hard to free B12 from food. It affects 8% to 9% of adults aged 65 and older. The Institute of Medicine estimated that 10% to 30% of older people may be unable to absorb the B12 that occurs naturally in food.

The gut can take up only a little at a time

Uptake through intrinsic factor is saturated (maxed out) at about 1.5 to 2 mcg per meal, EFSA says. The NIH puts the limit at 1 to 2 mcg. Above that, B12 crosses the gut wall by simple diffusion, which is far less efficient: 1% to 2% of the dose.

The NIH gives about 50% absorbed at doses under 1 to 2 mcg, about 2% at 500 mcg and 1.3% at 1,000 mcg. That works out to roughly 10 mcg and 13 mcg actually absorbed (our arithmetic from the NIH percentages), still several times the daily need. EFSA calls the often-used 50% absorption a likely overestimate at European intakes, and it uses 40% as a more careful figure.

The body keeps a store and recycles it

The body holds about 2 to 3 mg of B12 (range 1 to 6 mg), according to EFSA. Around half is in the liver. The NIH puts the store at 1 to 5 mg, or 1,000 to 2,000 times the amount typically eaten in a day. Daily losses are only 0.1% to 0.2% of the store.

The bile carries B12 into the gut every day. An assumed 50% to 80% of it is taken up again, which needs intrinsic factor. Without intrinsic factor, all of the bile B12 is lost in stool.

So deficiency develops faster in pernicious anemia than in someone who simply eats no B12. Even then, EFSA says deficiency can take years to develop.

What has been seen in people

The clearest human findings are about status. B12 pills correct a low B12, whether swallowed or injected. Metformin lowers it, and acid-reducing drugs are linked with deficiency.

Adding B12 to folic acid lowers homocysteine a little further, but lowering homocysteine did not prevent heart attacks or cancer. Trials in generally healthy adults found no clear gain for memory or mood. The NIH says B12 does not improve performance in people who have enough.

Trials in pregnancy and in children show better B12 status without a clear change in growth or development. All of these are among the study cards.

How much vitamin B12 do you need?

Adults need 2.4 mcg of vitamin B12 a day. That is the US recommended dietary allowance (RDA), an amount that covers nearly all healthy people. It is 2.6 mcg in pregnancy and 2.8 mcg while breastfeeding. EFSA’s adequate intake in the EU is higher: 4 mcg for adults, 4.5 mcg in pregnancy and 5 mcg when breastfeeding.

The two numbers differ because the panels worked from different evidence. The US RDA rests on the amount needed to keep blood counts and serum B12 normal, and it includes an assumed 50% absorption.

EFSA looked at four biomarkers together (serum B12, holotranscobalamin, methylmalonic acid and homocysteine). It could not set an average requirement. It set 4 mcg because intakes at or above that went with healthy readings on all four. Adults in several EU countries eat 4.2 to 8.6 mcg a day.

For pregnancy and breastfeeding, EFSA assumed 40% absorption. In the US, men get a mean of 5.84 mcg a day from food and women 3.69 mcg. Only 5% of men and 11% of women are below the 2 mcg average requirement.

For babies, the US adequate intake is 0.4 mcg in the first 6 months and 0.5 mcg from 7 to 12 months. It was set from the B12 in the breast milk of mothers with adequate B12 status.

Older adults and some other groups need extra thought. The Institute of Medicine estimates that 10% to 30% of older people may be unable to absorb food B12. So it advised that people over 50 meet most of their RDA from fortified foods or a supplement. The free B12 in those does not need stomach acid.

People with pernicious anemia need B12 under a doctor’s direction. So do people with Crohn’s disease of the last part of the small intestine, or a stomach removal, gastric bypass or ileal resection. Infants of vegan mothers should be given B12 from birth at the adequate intake.

Vitamin B12 deficiency: signs and who is at risk

The main signs of low B12 are megaloblastic anemia (large, abnormal red blood cells), fatigue, pale skin and palpitations, according to the NIH. Others are an inflamed tongue (glossitis), weight loss, numbness and tingling in the hands and feet, dementia and infertility. Nerve damage can occur without anemia and can become irreversible if it is not caught early.

The NIH adds that some studies link low B12 with depression. In pregnant and breastfeeding women, deficiency might cause neural tube defects, developmental delay and anemia in the child. Symptoms can take years to appear because of the body’s store.

The NIH lists the groups most at risk. Older adults are at risk, with deficiency in 3% to 43%, depending on the definition. So are people with pernicious anemia, gut disease such as celiac disease, or gastrointestinal surgery. Also at risk are people on metformin or acid-reducing drugs, vegetarians and vegans, and infants of vegan mothers.

Pernicious anemia is the most common cause of clinically evident deficiency worldwide. In the US it affects an estimated 151 per 100,000 people. Nitrous oxide (laughing gas) misuse is another cause, because it inactivates B12. In 20 patients with the resulting nerve and spinal cord damage, the mean serum B12 was normal while homocysteine was high.

Doctors usually start with serum B12, and most labs call a value under 200 or 250 pg/mL subnormal. If it is between 150 and 399 pg/mL, methylmalonic acid can help to confirm deficiency. In US data, 3.6% of adults were below 200 pg/mL, but 12.5% were below 300 pg/mL. So the cutoff changes the count a lot.

Treatment is a doctor’s call. Injections bypass absorption problems, and high oral doses may work too (see the Cochrane review in the study cards). Symptoms alone cannot tell low B12 from other causes, so ask for a blood test.

Forms of vitamin B12: absorption and effects

Vitamin B12 comes in four main forms: cyanocobalamin, methylcobalamin, adenosylcobalamin and hydroxocobalamin. Methylcobalamin and adenosylcobalamin are the active forms in the body. The other two are converted into them once inside the cell, according to the NIH.

EFSA adds that cells strip off the attached group first and then remake the two active forms, whichever form came in. Cyanocobalamin is the most common form in supplements. The NIH says no evidence indicates that absorption in supplements varies by form. It is about 50% at doses under 1 to 2 mcg, and much lower above that.

The honest bottom line: no trial we found shows that methylcobalamin or adenosylcobalamin is absorbed better or corrects deficiency better than cyanocobalamin. A 2015 review of the biochemistry concluded they are unlikely to be better. The route and the dose matter more.

High oral doses, injections and a tablet under the tongue all raised B12 in small trials, with no clear winner. Among the benefit trials, only the macular degeneration trial names its form (cyanocobalamin); the other abstracts do not. We found no trial of adenosylcobalamin against other forms.

Form	Activity or conversion	What studies show	Source
Cyanocobalamin	Becomes active after it is converted to methylcobalamin or adenosylcobalamin. Most common form in supplements.	The form in the dose-finding trial (647 to 1,032 mcg a day fixed mild deficiency), in the 2 mg oral against injection trial, and in the macular degeneration trial. The Institute of Medicine says B12-deficient people at risk of Leber’s optic atrophy, a genetic disorder it links to chronic cyanide intoxication, should not be given it. Hydroxocobalamin is a cyanide antagonist.	1, 3, 5, 6, 15
Methylcobalamin (mecobalamin)	An active form in the body. Cells make it from any form (EFSA), so the pill need not contain it.	Oral 1,000 mcg matched hydroxocobalamin injections after gastric bypass (50 patients). A year of 1 mg a day helped nerve tests in a trial of 90 people with diabetic neuropathy. A meta-analysis of mecobalamin trials in nerve disease found a mixed result. No trial we found compared it with cyanocobalamin for absorption or deficiency.	1, 2, 4, 7, 10, 11
Adenosylcobalamin	An active form in the body (mitochondria).	We found no head-to-head human trial against other forms. EFSA and the 2015 review say cells process it by the same route as the others.	1, 2, 4
Hydroxocobalamin	Becomes active after it is converted. Given by injection.	Used for injections in the gastric bypass trial. A pilot of 1,500 mcg given in the nose raised mean plasma B12 eightfold within an hour in 6 patients. The Institute of Medicine notes that acne reports with high-dose injections were mostly with this form.	1, 3, 7, 9
Free B12 in fortified foods and supplements	Already free of protein, so it needs no stomach acid to be released.	Bread with 9.6 mcg raised serum B12 by 49% in 12 weeks. In older adults with atrophic gastritis, regular fortified foods went with better B12 but did not restore it to normal. Absorption of crystalline B12 does not fall with age, the Institute of Medicine says.	1, 3, 12, 13
Sublingual tablets (any form)	The same vitamin, taken under the tongue.	Under the tongue and swallowed 500 mcg tablets raised B12 equally in 30 people. The NIH says evidence suggests no difference between oral and sublingual.	1, 8
Nasal gel (prescription)	The same vitamin, given in the nose.	In a small study of 10 older adults, 1,000 mcg given in the nose had about 2% bioavailability, similar to an oral dose, according to the NIH.	1
Injection	Bypasses the gut.	Usual treatment when absorption is badly impaired. Oral 1,000 to 2,000 mcg a day matched injections in the Cochrane review of 3 trials.	1, 14

Here are the head-to-head and form-specific studies, strongest evidence first, 7 in all. Note that the trials of pills against injections change the route, not just the form.

Is vitamin B12 safe? Supplements, dose and interactions

There is no tolerable upper intake level (UL) for vitamin B12 in the US. The Institute of Medicine found too little evidence of harm to set one. The NIH says it is generally considered safe even at high doses.

EFSA, relying on the earlier EU scientific committee, likewise found no adverse effects it could use to set an upper level. It notes that daily doses of 1 to 5 mg by mouth or injection showed no adverse effects. They had been given for long periods to people with absorption problems. The Institute of Medicine suggests the low toxicity may be explained by the small share of a large oral dose that is absorbed.

• Side effects. The Institute of Medicine found no adverse effects from food or supplements in healthy people. Some studies link injected doses of 0.5 to 5 mg with acne, mostly with hydroxocobalamin. It noted that iodine in some preparations may have been responsible.
• Cancer questions. In the VITAL cohort, men taking individual B12 supplements above 55 mcg a day for 10 years had about double the lung cancer risk. In two Norwegian trials and the B-PROOF trial, folic acid plus B12 went with more cancer. The NIH points out that the folic acid, not the B12, may explain the B-PROOF result. A meta-analysis of 18 trials found no effect on cancer. A high B12 level in a blood test may also be a marker of an undiagnosed cancer rather than a cause. If your result is high and you are not taking B12, ask a doctor.
• Metformin. In a trial, it lowered B12 by 19% over 4.3 years and raised the chance of deficiency by 7.2 percentage points. In the Diabetes Prevention Program follow-up, borderline-low B12 was more common after metformin. At 5 years it was 19.1% against 9.5%, and at 13 years 20.3% against 15.6%. Do not stop metformin on your own; ask about a B12 test.
• Acid-reducing drugs. Proton pump inhibitors (PPIs) and H2 blockers can slow stomach acid and lead to B12 deficiency, the NIH says. In a large case-control study, two or more years of PPIs went with 65% higher odds of a deficiency diagnosis. For H2 blockers it was 25%.
• Leber’s optic atrophy. The Institute of Medicine advises that B12-deficient people at risk of this inherited eye disorder should not be treated with cyanocobalamin. It may raise the risk of irreversible nerve damage. Hydroxocobalamin is not associated with this problem.
• Who should ask a doctor. Ask if you have symptoms of low B12, pernicious anemia, bowel or stomach surgery or Crohn’s disease. Ask too if you have been on metformin or acid reducers for years, or if you are vegan and pregnant or breastfeeding. In US survey data, older adults with low B12 and high folate had more anemia and cognitive impairment, which does not prove cause.

How to get more vitamin B12

• Eat B12 foods through the week. In our ranking, oysters give 13.6 mcg per 3 oz, herring 11.6 mcg, mackerel 9.8 mcg per fillet and sardines 8.2 mcg per can. The NIH lists beef liver at 70.7 mcg per 3 oz. Milk adds 1.3 mcg per cup. The intrinsic factor route handles only about 1 to 2 mcg per meal, the NIH says, so a bigger serving is not absorbed in proportion.
• If you are over 50, or take metformin or acid reducers, add fortified foods or a supplement. Free B12 does not need stomach acid. The Institute of Medicine advises older adults to get most of their RDA from fortified foods or a supplement. Check the label of cereals and nutritional yeast for the amount.
• If you eat no animal foods, do not rely on plants alone. The NIH says fortified foods and supplements can substantially lower the risk of deficiency in vegans. In the EPIC-Oxford cohort, 52% of vegan men had low B12. A review of 40 studies found vegans who take no supplements at especially high risk. Nori, spirulina and chlorella are not proven substitutes.

History of vitamin B12

The story starts with a deadly disease. Pernicious anemia was first described in 1849. Reports through the 19th century built a clear picture of it, including severe nerve damage that led to paralysis and death.

In 1926, George Minot and William Murphy gave patients a special diet with large amounts of liver. All of them improved in clinical and blood tests. They shared the 1934 Nobel Prize in Physiology or Medicine with George Whipple “for their discoveries concerning liver therapy in cases of anaemia”.

The next advance came from William Castle. He found that a stomach factor, which he called intrinsic factor, was missing in pernicious anemia. In 1948, two groups isolated the vitamin from liver at about the same time, and one of them published Crystalline Vitamin B12 in Science.

The vitamin was crystallized and characterized in Dorothy Hodgkin’s laboratory, and she determined its structure by X-ray methods in 1956. She received the 1964 Nobel Prize in Chemistry for her structure work.

Early clinical reports also recognized that B12 deficiency causes a severe neuropathy (nerve damage). Post-mortem studies showed loss of the insulating coat of the spinal cord. How B12 prevents these irreversible nerve lesions is still unclear, according to a 2012 history of the vitamin.

Frequently asked questions about vitamin B12

Can vegans get enough vitamin B12 without supplements?

Not reliably. Vitamin B12 is not naturally in plant foods, the NIH says. So vegans need fortified foods, such as some cereals and nutritional yeasts, or a supplement. In the EPIC-Oxford cohort, 52% of vegan men had a serum B12 under 118 pmol/L, against 7% of vegetarians. Stores can last years, so a shortfall can take a long time to show. Nori, spirulina and chlorella are not proven substitutes.

How much vitamin B12 can you take in a day?

There is no official upper limit. The US panel found too little evidence of harm to set one, and EFSA found no adverse effects to base one on. Doses of 1,000 to 2,000 mcg a day by mouth are used to treat deficiency. At that size, only about 1.3% to 2% is absorbed, according to the NIH. One cohort study linked individual B12 supplements above 55 mcg a day for 10 years with more lung cancer in men. That cannot show cause, so talk to a doctor about high doses over the long term.

Does vitamin B12 give you energy?

Only if you are low. The NIH says B12 does not appear to improve performance or endurance in people who have enough. In a Danish trial of 140 people with slightly raised methylmalonic acid, B12 injections changed only one of eight quality-of-life scores. The EU allows foods that are a source of B12 to say it contributes to the reduction of tiredness and fatigue. That is a statement about normal function, not a treatment.

Is methylcobalamin better than cyanocobalamin?

No trial we found shows that. The NIH says no evidence indicates that absorption varies by form. A 2015 review concluded methylcobalamin and adenosylcobalamin are unlikely to beat cyanocobalamin, because cells convert all forms. One trial of 50 gastric bypass patients found 1,000 mcg of oral methylcobalamin matched hydroxocobalamin injections. The Institute of Medicine says people at risk of Leber’s optic atrophy should not be given cyanocobalamin.

Is sublingual B12 better than tablets?

No difference was found. In 30 people with low B12, 500 mcg a day under the tongue or swallowed raised B12 in 4 weeks. It rose from about 100 to about 290 pmol/L. There was no difference between groups. The NIH also says evidence suggests no difference in efficacy between oral and sublingual (under-the-tongue) forms. Choose the one you will take consistently.

Why do older adults and people on metformin need to watch vitamin B12?

Older adults often cannot release B12 from food. The Institute of Medicine estimates that 10% to 30% may be unable to absorb it. The NIH says atrophic gastritis affects 8% to 9% of adults aged 65 and older. Metformin lowered B12 by 19% over 4.3 years in a trial. Two or more years of acid-reducing drugs went with higher odds of deficiency. Fortified foods and supplements bypass the problem because their B12 is already free.

Which foods are highest in vitamin B12?

In our USDA ranking, oysters lead with 13.6 mcg per 3 oz. Herring (11.6 mcg), mackerel (9.8 mcg per fillet) and sardines (8.2 mcg per can) follow. The NIH table adds beef liver at 70.7 mcg per 3 oz and clams at 17 mcg, which our 17-food ranking does not include. Fortified nutritional yeast can have 8.3 to 24 mcg per ¼ cup. Plants do not make B12 on their own.

Can vitamin B12 protect your memory?

Not in people with normal B12. A Cochrane review of 14 trials in 27,882 healthy adults found little or no effect on thinking skills. Another review, of 5 trials in 879 people with mild cognitive impairment, found no clear benefit. The VITACOG trial found slower brain shrinkage (0.76% against 1.08% a year) with a mix of B12, B6 and folic acid. But it is one trial. Low B12 itself can cause memory problems, so a deficiency is worth treating.