Vitamin B12: Are You Getting It?

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January 30, 2002 | 64,896 views

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For the most updated version of this article by Jack Norris, RD, who is also the Director of Vegan Outreach, click here: "Vitamin B12: Are You Getting It?"

By Jack Norris, RD Director


Society's reliance on using animals for food has caused tremendous amounts of suffering for the unfortunate victims of factory farms and slaughterhouses.

Many who advocate vegan diets do so in order to prevent the raising of farmed animals under what are currently atrocious conditions. For success in moving society away from a reliance on using animals for food by way of adopting vegan diets, it is of great importance for vegans to have optimal health and for vegan advocates to give the most responsible nutritional advice.

The overwhelming consensus in the mainstream nutrition community has been that plant foods do not provide adequate amounts of vitamin B12.

However, some vegan advocates believe that plant foods provide all the nutrients necessary for optimal health and do not concern themselves with their own vitamin B12 intake or the vitamin B12 intake of those to whom they promote the diet. It can often be an afterthought, if that.

Some of these people have developed classic neurological symptoms indicating a B12 deficiency -- symptoms that, luckily, cleared up after they started taking B12 supplements.

I sometimes feel that for every person the vegan movement persuades to become vegan, another vegan goes back to eating animal products. If this is true, why?

While many current vegans report feeling better, the most common complaint I hear from ex-vegans is that they didn't feel healthy. This seems logical: The people who feel good on the diet stick with it. The people who feel bad, don't.

Could it be that some of the people who go back are feeling the effects of reduced B12 status? Many vegans would not consider this a possibility because humans need very little B12 and the body stores it for many years.

The fact that vegans tend to have lower B12 levels than lacto-ovo-vegetarians or nonvegetarians is often countered with, "Few vegans have ever shown signs of B12 deficiency".

Add to this the fact that many vegan advocates believe that a vegan diet is the diet of our human ancestors, and one sometimes gets the impression that because (supposedly) few vegans have ever shown signs of deficiency, B12 must either be provided in plant foods, by our own bodies, or perhaps it's not really a necessary nutrient after all.

However, the common observation made that vegans who do not supplement with B12 rarely suffer from B12 deficiency might not be true because people either quit a vegan diet or start supplementing with B12 long before they allow B12 deficiency symptoms to progress to any serious degree.

The good news is that not only can vegans prevent B12 deficiency, they can ensure optimal B12 status, possibly reducing their risk for heart disease and cancer, by following the recommendations provided here.

This article is a thorough review of the relevant scientific literature about vitamin B12 and a vegan diet in the past 20 or so years -- the good and the bad. Because it is so long, I have summarized recommendations for vegans in the box at the top of this page. I highly encourage vegan advocates who may otherwise not be interested in the details of vitamin B12, to read the table.

U.S. Dietary Reference Intake:

0-5 Months


6-11 Months


1-3 Years


4-8 Years


9-13 Years


14-50 Years


50+ Years






The average intake of B12 is approximately 5 g/day in the USA.49

Vitamin B12: A Pesky Molecule

Vitamin B12 deficiency in industrialized countries is rare.55 B12 is a complicated vitamin with a unique digestion, wide array of deficiency symptoms, and a number of "analogues" (molecules that appear to be B12, but actually are not) that possibly interfere with its function.

The B12 Molecule

B12 is a co-enzyme: it is needed for enzymes to do their job of changing one molecule into another. As vitamins go, B12 is large. One part of its structure is known as the corrin nucleus. The corrin resembles the heme of hemoglobin.

In hemoglobin, the heme holds an atom of iron. In B12, the corrin holds an atom of cobalt. The corrin plus other atoms make up the part of B12 known as a cobalamin. In order to be true B12, the cobalamin must have one of a number of attachments.

Depending on the attachment, cobalamin becomes cyanocobalamin, hydroxocobalamin, aquocobalamin, nitritocobalamin, methylcobalamin, or adenosylcobalamin (also called 5'-deoxyadenosylcobalamin).35

Only 2 cobalamins are active as co-enzymes in the human body: adenosylcobalamin and methylcobalamin. However, the body has the ability to convert most other cobalamins into one of these active forms. Cyanocobalamin is the form most often found in vitamin tablets because it is one of the most stable forms of cobalamin and the body readily converts it into one of the useable co-enzymes.47

There are many molecules that contain a corrin nucleus but that are not cobalamins. And some cobalamins might not be useable by the human body.

Digestion & Absorption of B12

Microorganisms, primarily bacteria, are the only known organisms that manufacture B12.

These bacteria often live in bodies of water and soil. Animals get B12 by eating food and soil contaminated with these microorganisms. These bacteria also live inside animals' digestive tracts.

Plants do not require B12 for any function, and therefore have no mechanisms to produce or store B12.

In animals, B12 is normally attached to a protein (very large molecules made up of amino acids) either for transport or storage.

B12 is generally found in all animal products. When humans eat animal foods, the B12 is bound to protein. When the protein-B12 complex reaches the human stomach, the stomach secretes acids and enzymes that detach the B12 from the protein. Then, in a process unique to B12, another protein, R protein picks up the B12 and transports it through the stomach and into the small intestine. R protein is found in many fluids in the human body including saliva and stomach secretions. R protein picks up all corrinoids in addition to true B12.45

The stomach cells also produce a protein called intrinsic factor (IF).

When the B12-R protein complex gets to the small intestine, B12 is liberated from the R protein by enzymes that are made in the pancreas.35 B12 then attaches to IF that has also made its way into the small intestine.

The IF then carries the B12 to the last section of the small intestine, the ileum. The cells lining the ileum contain receptors for the B12-IF complex. Calcium is thought to be needed by the B12-IF receptor in order to take the B12 into the intestinal cell. The B12-IF complex protects B12 against bacterial and digestive enzyme degradation.64

Free B12

In supplements, B12 is not bound to protein. In large doses obtained only through supplements, B12 can bypass the absorption process described above. Instead, passive diffusion can account for much absorption of the free B12.35 (Passive diffusion normally accounts for 1-3% of B12 absorbed when obtained through normal food sources.35)

Enterohepatic Circulation

About 60% of the total amount of B12 in the body is stored in the liver and 30% is stored in the muscles.64 The body has a special circuit between the digestive tract and the liver. Bile, which is made in the liver and needed to digest fat, is secreted into the beginning of the small intestine. It is then reabsorbed at the end of the small intestine and taken back to the liver where it is used again. This circuit is called enterohepatic circulation.

Omnivores normally eat about 2-6 g of B12/day and their liver normally excretes 5-10 g/day via their bile.48 Healthy omnivores reabsorb about 3-5 g B12 from the bile.48 A (noninfant) vegan with B12 absorption problems will develop B12 deficiency in 1-3 years because absorption problems will block the enterohepatic circulation.48 Adult vegans decrease their bile excretion to as low as 1 g/day and reabsorb almost 100% of it, thus delaying B12 deficiency for 20-30 years.48

Enterohepatic circulation can help remove B12 analogues (especially noncobalamin corrinoids) that find their way into circulation by dumping them in the intestine where they will not be picked up by IF, and will therefore be excreted.47

Pernicious Anemia

As mentioned above, without IF, only about 1-3% of the ingested B12 is absorbed.37 This is typically not adequate and results in a macrocytic anemia. When macrocytic anemia is caused by a lack or malfunction of IF, it is known as pernicious anemia (PA). PA can occur in inflammation of the stomach, when most or all of the stomach has been removed, or when the last part of the ileum has been removed.37

Transport in the Blood

After B12 is absorbed into the intestinal cells, it attaches to another R protein, transcobalamin 2 (TC2). TC2 is made in the intestinal cells48 and transports B12 to all body tissues through the blood. All body tissues have receptors for TC2. Once the B12-TC2 complex arrives at the cell where it is needed, B12 is released from TC2 in the form of hydroxocobalamin.

It is then turned into methylcobalamin or adenosylcobalamin35 and used for their respective enzymes. TC2 normally contains about 20% of B12 in the blood, also called serum B12 (sB12) or plasma B12. When intake of B12 into the intestine slows, B12-TC2 levels fall rapidly.48 If TC2 lacks B12, the vitamin will not be delivered, regardless of whether the total sB12 is low, normal, or high.46

TC2 is depleted of B12 within days after absorption stops making the measurement of the B12-TC2 complex the best screening test for early negative B12 balance. B12-TC2 falls below normal long before sB12 falls below normal. TC1 and TC3 (also called haptocorrin46) are the proteins that normally store the other 80% of the B12 in the blood.48

Functions of B12

Homocysteine Clearance

Homocysteine (Hcy) is a nerve and vessel toxin (promoting heart attacks, thrombic strokes, and vessel blockages) at elevated levels.48 When B12 is no longer delivered to certain brain cells, Hcy builds up.48

Thus, the body has a need to turn Hcy into other molecules, one of which is methionine (an amino acid). If it cannot do this, Hcy levels build up in the blood. Methylcobalamin (a form of B12) is needed by the enzyme that converts Hcy into methionine. If someone is B12 deficient, Hcy levels will increase.
Elevated Hcy can also happen with deficiencies in vitamin B6 or folate.48 RDA amounts of the deficient vitamin can reduce Hcy levels to normal if a vitamin deficiency is the cause.48

Folate and DNA

The vitamin folate (also called folic acid) comes into play in B12 deficiency. Folate is needed to produce DNA. In creating methylcobalamin (used in the Hcy to methionine reaction mentioned above), B12 takes a methyl group from one form of folate. In so doing, it produces a form of folate needed to make DNA. If there is no B12 available, this form of folate can become reduced (known as the methyl-folate trap) and DNA cannot be produced.74

However, if there is enough incoming folate through the diet, the body can use the new folate to produce DNA. In a B12 deficiency, the accumulation of 5-methyl THF (a form of folate) and folic acid can occur.99 This could explain some of the high folate levels found in vegans.

Folate and DNA play a critical role in rapidly producing cells. For example, the
production of red blood cells involves dividing large, inactive cells into smaller, active cells. Because of the methyl-folate trap, people with a B12 deficiency can sometimes have large red blood cells.

People with a folate deficiency can also have large red blood cells. This problem is known as megaloblastic anemia or macrocytic anemia (depending on how the large red blood cells are measured).

Megaloblastic anemia is measured by determining the quantity of large red blood cells.

Macrocytic anemia is determined by the average volume of the red blood cells, known as mean corpuscular volume (MCV). In B12 deficiency, there may be high enough folate levels to allow red blood cell division to continue, preventing macrocytic anemia.

To add insult to injury, an iron deficiency (which results in small red blood cells) can counteract the large red blood cells making it appear as though the blood cells are normal in the face of multiple nutritional deficiencies.46

B12 helps transport and store folate in the cells. When serum B12 is low, folate is unable to be stored in the cells and it starts to accumulate in the serum, increasing serum folate levels.39

Intestinal cells are also rapidly dying and being replaced. Ironically, a B12 deficiency can make itself worse because it can prevent the production of the intestinal cells needed to absorb B12.

Methylmalonic Acid (MMA)

There is one metabolic pathway in which B12 is the only co-enzyme: the conversion of one molecule, methylmalonyl-CoA, to another molecule, Succinyl-CoA. When B12 is not available, methylmalonyl-CoA levels increase. Because it is toxic, methylmalonyl-CoA is converted to methylmalonic acid (MMA) which then accumulates in the blood and urine. Since this reaction only requires B12 as a co-enzyme,

MMA levels are excellent indicators of B12 status. Rare genetic defects can also cause high MMA levels.

Macrocytic Anemia: Not a Reliable Test for B12 Deficiency

Traditionally, the existence of macrocytic anemia was relied on to indicate a B12 deficiency. However, neurological disorders due to B12 deficiency commonly occur in the absence of a macrocytic anemia.

On the other hand, measurements of serum MMA and Hcy, both before and after treatment with B12, are useful in the diagnosis of such patients with B12 deficiency.

Lindenbaum et al.60 (1988, USA) examined cases of B12 deficiency at two hospitals from 1968-1985. Among the 141 patients with neurological problems due to B12 deficiency, 40 (28%) had no anemia or macrocytosis. MCV was normal in 25.

Characteristic features of patients with B12 deficiency but without macrocytic anemia included: sensory loss, inability to move muscles smoothly (ataxia), dementia, and psychiatric disorders.

They had high levels of serum MMA and Hcy (35 out of 37 had 3 standard deviations above the average for both). They also had borderline (and sometimes normal) sB12. Serum B12 levels were > 200 pg/ml in 2 patients, between 100-200 pg/ml in 16, and < 100 pg/ml in 22. One patient died during the first week of treatment, but the other 39 benefited from B12 therapy. Some patients had residual abnormalities after years of treatment.

Measuring B12 in the Body and in Food

Traditionally, B12 has been measured by "feeding" B12 to certain bacteria and seeing if those bacteria are able to thrive on it. This is known as microbiological assay. However, many bacteria used in these assays also thrive on noncobalamin corrinoids.48

B12 has also been measured through radioassay (which has other names, such as competitive binding assay) by seeing whether it binds to R protein. It is now known that R protein can bind to noncobalamin corrinoids. So, these methods that were once thought to measure only B12 are now known to measure B12 analogues also.

Despite this, some laboratories continue to rely on these methods to measure the B12 content of foods and the body (although it is becoming less common). Radioassays using IF as the binding agent have proven more accurate because IF does not measure noncobalamin corrinoids. However, problems have also been found even when using IF radioassays (as will be discussed in more detail later).

IF from pigs is normally used for these radioassays, and there could be a slight possibility that pig IF is selective for B12 analogues that human IF would not select.

Stages of B12 Deficiency

von Schenck et al.103 (1997) reported that the average adult stores 3000 g B12, while losing only about 3 g/day. Herbert48 (1994) reports that when one stops eating B12, they pass through 4 stages of B12 deficiency as follows:

Depletion Stages:

Stage 1 Serum depletion: Shown by low amounts of B12 on TC2; also can be measured by lower than normal B12 in red blood cells since only young red blood cells contain B12.

Stage 2 Cell depletion: Shown by low TC1+TC3 and low B12 in red blood cells; low total serum B12 levels (i.e., TC1 + TC2 + TC3) are a relatively late indicator.

Deficiency Stages:

Stage 3 Biochemical deficiency: Shown by slowed DNA synthesis, elevated serum Hcy and MMA.

Stage 4 Clinical deficiency: Megaloblastic anemia, nerve damage, etc.
Because liver cells store more B12 than bone marrow or nervous tissue, liver cells can be in Stage 2 while bone marrow (which makes red blood cells) and nervous tissue is already in Stage 3 and possibly even 4.48

Herbert says that vegans can stabilize in Stage 2 for years because depleted stores trigger increased absorption, making more efficient the absorption of the trace amount of B12 from bacterial contamination in the small intestine and B12 secreted in the bile. Stage 2 will move on to Stage 3 much sooner in people with B12 absorption problems. The slight negative balance of vegans will eventually deplete stores and Stage 3 will be entered.


Neurological Symptoms

Neurological symptoms are the biggest worry in B12 deficiency because they can be irreversible. However, if caught early enough, they can be reversed in many cases.

One theory of why nerve problems occur in B12 deficiency is from a lack of methionine (from B12 not converting Hcy back into methionine) which creates a lack of S-adenosylmethionine (SAM).35 SAM is required for the production of phosphatidylcholine36 which is part of the myelin (the fatty material that insulates many nerves).

Phosphatidylcholine improves nerve transmission.36

Another theory is that the altered nerve function of B12 deficiency is possibly due to the body's inability to convert methylmalonyl-CoA (a 3 carbon molecule) to succinyl-CoA (a 4 carbon molecule). This inability results in a build up of propionyl-CoA (a 3 carbon molecule).

Fatty acids are normally made by adding 2 carbons at a time to an even numbered carbon molecule. In an overabundance of 3 carbon molecules, large amounts of unusual 15-carbon and 17-carbon fatty acids could be produced and incorporated into nerve sheets, causing altered nerve function.103

Early Signs of B12 Deficiency

According to Crane et al.18 (1994, USA), the usual vegan patient has no clinical symptoms or signs of inadequate B12. Early manifestations are unusual fatigue, faulty digestion (no appetite or nausea) and loss of menstruation.

Other symptoms are nervousness, numbness and tingling of the hands and feet, mild depression, striking behavioral changes, paranoia, hyperactive reflexes, fever of unknown origin,18 frequent upper respiratory infections,19 impotence, impaired memory,49 infertility,55 sore tongue, and diarrhea.60

6 Ways to Get B12 Deficiency

Herbert48 (1994) reports the ways to get B12 deficiency as follows:

1. Inadequate dietary intake.
2. Inadequate absorption:

Loss of IF: This is genetically predetermined and age-dependent (sometimes as early as 45 yrs). It is the most common cause of B12 deficiency in nonvegetarians. Because of their lower stores, vegans will more rapidly express a genetically predisposed B12 deficiency.

Loss of gastric acid and/or protein digesting enzymes which break the protein-B12 bonds in food. According to Ho49 (1999), this can be caused by stomach surgery, atrophy or inflammation of the stomach, medications that suppress acid secretion, or a stomach infection by H. pylori or anaerobic bacteria.

Pancreatic disease that reduces free calcium in the ileum. This can be improved by giving calcium and/or bicarbonate.

Unhealthy ileum.

The oral, diabetic drug metformin ties up free calcium in the intestines producing B12 malabsorption.

Autoimmunity to IF: Circulating antibodies to IF indicate eventual PA if not treated. A chronic B12 deficiency damages immune function and the antibodies may disappear as B12 deficiency progresses.

1.a Inadequate utilization: Defects in B12 enzymes, transport proteins, or storage proteins.
1.b Increased requirement during pregnancy or hyperthyroidism.
1.c Increased excretion caused by alcoholism.
1.d Increased destruction: Megadoses of vitamin C can create free radicals which can damage B12 and IF. Nitrous oxide anesthesia in people who are low in B12 (nitrous oxide can change the cobalt atom of B1235).

Others causes of B12 deficiency are tapeworms,35 hypothyroidism (this relationship is possibly autoimmune),53 Giardia lamblia infection, chronic use of gastric acid secretion suppressors, or drugs affecting absorption (including cimetidine, metformin, potassium chloride, and cholestyramine).98

Alcoholism & AIDS

B12 deficiency can be masked by alcoholism because excess B12 is released into the blood from the damaged liver.48 AIDS can cause B12 deficiency as shown through macrocytic anemia and neurological problems, but without elevated Hcy levels.

Correcting & Preventing Deficiency

According to Herbert, measuring MMA or Hcy levels will not prevent deficiency. Instead, depletion must be measured by way of low B12-TC2 levels. Depletion precedes deficiency by months to years in over 95% of the cases.48 It only takes .1 g of B12 to start reversing deficiency symptoms, though the response can be improved with more.47

Small Amounts of Animal Products Not Enough to Restore Optimal B12 Status

van Dusseldorp et al.102 (1999, Netherlands) investigated whether moderate consumption of animal products is sufficient for achieving normal B12 function in 73 adolescents (in good health) who had received a macrobiotic diet until 6 years of age and had then switched to a LOV or omnivorous diet. 94 nonvegetarian (NV) adolescents from birth were used as a reference. In macrobiotics, dairy products supplied on average 0.95 g B12/day.

Additionally, they consumed fish, meat, or chicken 2-3 times/week. Serum B12 was significantly lower and MMA, folate, and MCV were significantly higher in macrobiotics. Of macrobiotics, 21% had abnormal MMA levels, 10% had abnormal total homocysteine, and 15% had abnormal MCV (> 89 fl). Authors concluded that a substantial number of the formerly strict macrobiotic adolescents still had impaired B12 function.

Thus, moderate consumption of animal products is not sufficient for restoring normal B12 status in adolescents with inadequate B12 intake during the early years of life. They might need B12 intakes higher than recommended to obtain normal B12 status.

Supplements, Fortified Foods, & Animal Products

Tucker et al.98 (2000, USA) examined the B12 status of 2999 subjects in the Framingham Offspring Study. Average sB12 for the entire group was 473 pg/ml. 39% of subjects had sB12 < 348, 17% < 250, and 9% < 200 pg/ml. There was a significant trend towards lower B12 levels with increased age.

In contrast with previous reports, sB12 was associated with B12 intake. Supplement users were significantly less likely than non-supplement users to have B12 < 250 pg/ml (8% vs. 20%). Among non-supplement users, those who consumed fortified cereal over 4 times/week were significantly less likely to have B12 < 250 pg/ml.

Those in the highest one-third vs. lowest one-third of dairy intake were significantly less likely to have B12 < 250 pg/ml (13% vs. 24%). There was no difference between meat intake groups. Tucker et al. concluded that the use of supplements, fortified cereal, and milk appears to protect against lower SB12.

This could be because additional sources may have increased total intake and/or some sources may be more bioavailable. Meat, eggs, and seafood may not be as protective as dairy because cooking may destroy B12. There was a clear and strong increase in B12 levels with greater B12 intake up to about 10 g/day.


In 1988, Herbert cautioned that large amounts of B12 may eventually be found to be harmful.47 However, Hathcock & Troendle40 (1991) point out that there appears to be little or no question that B12 intakes of 500-1000 mcg/day are safe. The cobalt and the cyanide contribution of 1000 mcg/day of cyanocobalamin are toxicologically insignificant.40

Crane et al.18 (1994, USA) noted that tablets of one vitamin company dissolved slowly in water and acid. They then conducted a study to see if vegan patients who had not responded to oral B12 tablets could improve their B12 response by chewing the tablets. 7 participants chewed the tablets of 100 mcg (once a week for 6 weeks) and their average levels went from 116 to 291 pg/ml.

Of the 9 who didn't chew, levels increased from 123 to 139 pg/ml. These 9 then chewed 500 mcg/day for 10 days and their levels rose to normal with a final average of 524 " 235 pg/ml. 3 participants could not raise their levels orally and required injections to maintain sB12 above 300 pg/ml. Crane et al. recommend that vegans chew, or let dissolve in the mouth, a 100-500 mcg B12 tablet once a week or more often.

Supplements should not be left in the light as prolonged light causes irreversible destruction of cyanocobalamin.89

Continued on Page 2

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