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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:
B12: Are You Getting It?"
By Jack Norris, RD
on using animals for food has caused tremendous amounts of
suffering for the unfortunate victims of factory farms and
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.
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
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.
Dietary Reference Intake:
The average intake
of B12 is approximately 5 g/day in the USA.49
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.
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.
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.
& Absorption of B12
primarily bacteria, are the only known organisms that manufacture
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.
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
stomach cells also produce a protein called intrinsic factor
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
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
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
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
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
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
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
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,
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
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
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
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
Folate and DNA
play a critical role in rapidly producing cells. For example,
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).
is measured by determining the quantity of large red blood
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
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.
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.
Anemia: Not a Reliable Test for B12 Deficiency
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
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.
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.
B12 in the Body and in Food
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
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
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.
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: 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.
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
deficiency: Shown by slowed DNA synthesis, elevated serum
Hcy and MMA.
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.
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).
improves nerve transmission.36
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
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
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.
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
Ways to Get B12 Deficiency
reports the ways to get B12 deficiency as follows:
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.
that reduces free calcium in the ileum. This can be improved
by giving calcium and/or bicarbonate.
The oral, diabetic
drug metformin ties up free calcium in the intestines producing
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.
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,
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.
& 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
Amounts of Animal Products Not Enough to Restore Optimal B12
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.
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.
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.
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.
not be left in the light as prolonged light causes irreversible
destruction of cyanocobalamin.89
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