VITAMIN B9

Name: Folic acid or folate is a B vitamin. It is also

referred

to

as vitamin

M, vitamin

B9, vitamin

Bc (or folacin), pteroyl-L-glutamic acid, and pteroylL-glutamate.

Food supplement manufacturers often use the
term folate for something different than "pure" folic
acid: in chemistry, folate refers to the deprotonated
ion, and folic acid to the neutral moleculewhich
both co-exist in water. (The International Union of
Pure and Applied Chemistry and the International
Union of Biochemistry and Molecular Biology state
that

folate

and

folic

acid

are

the

preferred

synonyms for pteroylglutamate and pteroylglutamic

[8]

acid, respectively. )

Folate indicates a collection of "folates" that is not

chemically

well-characterized,

including

other

members of the family of pteroylglutamates, or

mixtures of them, having various levels of reduction
of the pteridine ring, one-carbon substitutions and
different numbers of glutamate residues.
Folic acid is synthetically produced, and used
[9]

in fortified

foods and supplements. Folate

is

converted by humans to dihydrofolate (dihydrofolic

acid), tetrahydrofolate (tetrahydrofolic

acid),

and

other derivatives, which have various biological

activities.

[10]

Vitamin

B9 is essential for

numerous bodily

functions. Humans cannot synthesize folates de

novo; therefore, folic acid has to be supplied

through the diet to meet their daily requirements.
The human body needs folate to synthesize DNA,
repair DNA, andmethylate DNA as well as to act as
a cofactor in certain biological reactions.
especially

important

divisionand growth,

such

in

aiding
as

in

[11]

It is

rapid cell

infancy

and

pregnancy. Children and adults both require folate

to produce healthy red

blood

cells and

[12]

preventanemia.

Folate and folic acid derive their names from

the Latin word folium, which means "leaf". Folates

occur naturally in many foods and, among plants,

are

especially

vegetables.
A

lack

plentiful

in

dark

green

leafy

[13]

of dietary folates

can

lead

to folate

deficiency. A complete lack of dietary folate takes

months before deficiency develops as normal
[14]

individuals have about 50020,000 g

body stores.

[15]

of folate in

This deficiency can result in many

health problems, the most notable one being neural

tube defects in developing embryosa relatively
rare birth defect affecting only 300,000 (0.002%) of
births
folate

[16]

globally each year. Common symptoms of

deficiency

include diarrhea, macrocytic

anemia with weakness or shortness of breath,

nerve damage with weakness and limb numbness

[17]

(peripheral neuropathy),

pregnancy complications,

mental confusion, forgetfulness or other cognitive

deficits, mental depression, sore or swollen tongue,
peptic

or

mouth

ulcers,

headaches,

heart

palpitations, irritability, and behavioral disorders.

Low

levels

of

folate

to homocysteine accumulation.

can
[11]

Low

also
levels

lead
of

folate have been associated with specific cancers.

[11]

However, it is not clear whether consuming

recommended (or higher) amounts of folic acid

from foods or in supplementscan lower cancer
risk in some people.

Who Discover: In the 1920s, scientists believed

folate deficiency and anemia were the same
condition.

[86]

In 1931, researcher Lucy Wills made a

key observation that led to the identification of

folate

as

the

prevent anemia during

nutrient

required

pregnancy.

Dr.

to
Wills

demonstrated that anemia could be reversed

with brewer's yeast. In the late 1930s, folate was
identified as the corrective substance in brewer's
yeast.
It

was

first

isolated

in

and

extracted

from spinach leaves by Mitchell and others in 1941.

[87]

Bob Stokstad isolated the pure crystalline form in

1943, and was able to determine its chemical

structure while working at the Lederle Laboratories

of

the

American

Cyanamid

Company.

[88]

This

historical research project, of obtaining folic acid in

a pure crystalline form in 1945, was done by the
team called the "folic acid boys," under the
supervision and guidance of Director of Research
Dr. Yellapragada Subbarow, at the Lederle Lab,
Pearl River, NY.

[89]

This research subsequently led to the synthesis of

the antifolate aminopterin, the first-ever anticancer
drug, the clinical efficacy was proven by Sidney
Farber in 1948. In the 1950s and 1960s, scientists
began to discover the biochemical mechanisms of
action for folate.

[86]

In 1960, experts first linked

folate deficiency to neural tube defects.

[86]

In the

late 1990s, US scientists realized, despite the

availability of folate in foods and in supplements,
there was still a challenge for people to meet their
daily folate requirements, which is when the US
implemented the folate fortification program.

[86]

Introduction
Vitamin B9, also called folate, is one of the watersoluble B vitamins. The name comes from folium,
which is the Latin word for leaves, because folates
were first isolated from spinach.

Vitamin B9 can occur in different forms: the

naturally occurring folate, and folic acid, a
synthetic

folate

compound

used

in

vitamin

supplements and fortified food because of its

increased stability.
Health Functions
A sufficient intake of vitamin B9, occurring as folate
(in foods) and folic acid (in supplements), is
important as it helps the body as a coenzyme to

utilize amino acids, the building blocks of

proteins

produce nucleic acids (e.g., DNA), the body's

genetic material

form blood cells in the bone marrow

ensure

rapid

cell

growth

in

infancy,

adolescence, and pregnancy

control (together with vitamin B6 and vitamin

B12) blood levels of the amino acid homocysteine,
associated with certain chronic conditions such as
heart disease.
The European Food Safety Authority (EFSA), which
provides scientific advice to assist policy makers,
has confirmed that clear health benefits have been
established for the dietary intake of folate (vitamin
B9) in contributing to:

normal blood formation;

normal homocysteine;

a normal metabolism of the immune system;

normal cell division;

normal

maternal

tissue

growth

during

pregnancy;

normal amino acid synthesis;

normal psychological functions;

the reduction of tiredness and fatigue.

In addition, the EFSA has confirmed that

supplemental folate intake increases maternal folate
status, which contributes to the reduction of the risk
of neural tube defects (NTD).
Disease Risk Reduction

Birth

defects

Studies have found that women who take vitamin

B9 (folic acid) supplements before conception and
during the first four months of pregnancy (before a
woman may even know she is pregnant) may
reduce their risk of having children with neural tube
defects by 72100%. Folic acid may also help
prevent miscarriage, although the evidence is not
clear *.
Heart

disease

There is some evidence that getting enough vitamin

B9 (folate) in diet may reduce the risk of heart
disease.

However,

this

evidence

is

based

on population studies and not on definitive clinical

trials *.
In addition, because folic acid helps control levels
of an amino acid called homocysteine in the body,
and because homocysteine levels tend to be high
in people with heart disease, some researchers
theorize that lowering levels of homocysteine may
help

prevent

heart

disease,

heart

attack,

and stroke. However, more research is needed to

clarify the relationship between homocysteine, heart
disease, and the potential benefits of folic acid
supplements.

Cancer
Vitamin B9 (folate) appears to protect against the
development of some forms of cancer, particularly
cancer of the colon and the breast. However, this
evidence is based on population studies that show
people who get enough folate in their diet have
lower rates of these cancers. Presently, there is no
proof that taking folic acid supplements helps
prevent cancer *.
Alzheimers

disease

People who have Alzheimer's disease often have

low levels of folic acid in their blood, but it is not
clear whether this is a result of the disease or if
they are simply malnourished due to their illness.

There is some evidence that consuming adequate

amounts of vitamin B9 either in the diet or by
supplementation could be beneficial to the aging
brain and help protect it against Alzheimer's and
other forms of dementia.
*

see

also Principles

The

complexity

of

micronutrient research
Other Applications

Please note:
Any dietary or drug treatment with high-dosed
micronutrients needs medical supervision.

Depression
Some studies show that 1538% of people with
depression have low folate levels in their bodies,
and those with very low levels tend to be the most
depressed. Low levels of folic acid have also been
associated

with

antidepressants.

More

poor
research

response

to

is

to

needed

understand the link; it appears that folic acid may

help enhance the effect of antidepressants, at least
in some people, but folic acid itself is not a
replacement for antidepressants.
Intake Recommendations
While in Europe the recommended intakes for
vitamin B9 (folate) varies between 200 and 400

micrograms (mcg) per day for adults in different

countries, in the U.S., 400 mcg/day for adults, 600
mcg/day during pregnancy, and 500 mcg/day for
breast-feeding

women

have

been

defined

as

adequate.
Supply Situation
In most European countries, the average vitamin B9
(folate) intake is below national recommendations.
In the U.S., less than half of women who become
pregnant follow the recommendation, despite the
effectiveness

of

vitamin

B9

(folic

acid)

supplementation in preventing neural tube defects.

Deficiency

Folate deficiency is one of the commonest vitamin

deficiencies. It can result from inadequate intake,
defective

absorption,

abnormal

metabolism

or

increased requirements.
Early symptoms of folate deficiency are non-specific
and may include tiredness, irritability and loss of
appetite.

Severe

folate

deficiency

leads

to

megaloblastic anemia, a condition in which the

bone marrow produces oversized immature red
blood cells.
Pregnant and breast-feeding women are at a higher
risk of vitamin B9 deficiency: due to rapid tissue
growth during pregnancy and to losses through the

milk during breast-feeding, an increased folate/folic

acid intake is required. In pregnant women, vitamin
B9

deficiency

can

result

in

devastating

and

sometimes fatal birth defects (e.g., neural tube

defects).
Sources
Folates are found in a wide variety of foods. Its
richest

sources

are

liver,

dark

green

leafy

vegetables, beans, wheat germ and yeast. Other

sources are egg yolk, milk and dairy products,
beets, orange juice and whole wheat bread.
Safety
No adverse effects have been associated with the
consumption of excess dietary vitamin B9 (folate).

Prostate

cancer

risk

A study has indicated a higher incidence of prostate

cancer after several years intake of vitamin B9
(folic acid) supplements. However, experts have
raised serious doubts about these conclusions
because of invalid study design (see also Expert
Opinion).
Lung

Cancer

Risk

A study has suggested that patients with heart

disease have an associated increased risk of lung
cancer and mortality with doses of vitamin B9 (folic
acid) and vitamin B12 supplements. However,
experts criticized that the study is inconsistent with

current evidence showing that higher average folic

acid intake in adults is related to lower cancer
incidence and a 50% reduction in mortality from
cancer. The findings would nullify the long-term
benefits that folic acid fortification may have on
population health.
Tolerable

upper

intake

level

To avoid potential adverse effects health authorities

in Europe and the U.S. have set a tolerable upper
intake level for vitamin B9 of 1 mg per day for
adults.
Drug

Please note:

interactions

Because of the potential for interactions, dietary

supplements should not be taken with medication
without first talking to an experienced healthcare
provider.

Why is vitamin B9 important?

According

to
1

the

Association , vitamin B9 (folic

British
acid

Dietetic
and

folate

inclusive) is vital for several bodily functions,

including:

Ball-and-stick model of the folic acid molecule

To synthesize DNA, RNA and to repair

Aiding rapid cell division and growth

To produce healthy red blood cells

It is important for pregnant women to have

enough folic acid to prevent major birth defects of
her baby's brain or spine (neural tube defects,
including spina bifida and anencephaly)

Enhances

brain

health.

Dutch

researchers

reported that folic acid supplementation

may

improve memory.
In 1992, the FDA (Food and Drug Administration)
advised fortifying the country's food supply with folic
acid. In 1998 folic acid started being added to
breads and other grains.

Natural sources
Dark green vegetables are good sources of folic
acid. Be careful not to overcook, as the folic acid
content can drop considerably.
The following foods are known to be rich in folic
acid:

Spinach is rich in folic acid

Asparagus

Baker's yeast

Broccoli

Brussel sprouts

Cabbage

Cauliflower

Egg yolk

Jacket potato (large)

Kidney

Lentils

Lettuce

Liver (pregnant women should not consume

liver)

Many fruits have moderate amounts, papaya

and kiwi have more

Milk

Oranges

Parsnips

Peas

Spinach

Sunflower seeds

Wholewheat bread (usually fortified).

Folic acid deficiency anemia

People can get folic acid deficiency anemia if they
do not eat enough foods which contain folic acid,
they require higher quantities of it and are not

taking them, such as pregnant and lactating

women, individuals with medical problems, such as
sickle cell disease, or the person's body does not
absorb enough of it, as may happen with alcohol
abuse or improper functioning kidneys.
Some

medications,

such

as

those

used

for

treating rheumatoid arthritis, cancer, and seizures

may raise the risk of folic acid deficiency anemia.
The signs and symptoms of folic acid deficiency
disease include:

Fatigue, tiredness

Feeling generally weak

Forgetfulness

Being irritable, easy irritated

Loss of appetite

Weight loss.

Patients with folic acid deficiency anemia are given

folic acid pills to be taken daily.
Other risks
Apart from anemia and birth defects, folic acid
deficiency can result in:

A higher risk of second heart attacks

A higher risk of strokes. A study in the medical

journal circulation reported that adding folic acid
to foods contributes significantly to reducing
stroke death by lowering homocysteine levels, an
emerging risk factor for cardiovascular disease.

higher

risk

of

some

cancers,

such

as stomach cancer

A considerable drop in male sperm count, male

fertility. One study found that folic acid may
improve men's chances of fathering a child.

A higher risk of developing clinical depression

Possible memory and mental agility problems

Perhaps a higher risk of developing allergic

diseases

A higher long-term risk of lower bone density

(hypothesis).

The Medical Journal of Australia wrote in January

2011 that the prevalence of folate deficiency in the
country dropped considerably since the introduction

of compulsory fortification of wheat flour used in

bread-making.

VITAMIN B12

Other Names:
B-12,

B12,

Complex

Vitamin,

Cobalamin,

Cobalamine,

Cobamin,

Complexe

Vitaminique

B,

Bedumil,
Cobamine,

Cyanocobalamin,

Cyanocobalamine, Cyanocobalaminum, Cycobemin,

Hydroxocobalamin,
Hydroxocobalaminum,
Hydroxocobmine,

Hydroxocobalamine,
Hydroxocobemine,
Idrossocobalamina,

Methylcobalamin,

Mthylcobalamine,

Vitadurin,

Vitadurine, Vitamina B12, Vitamine B12.

VITAMIN B12 OVERVIEW INFORMATION

Vitamin B12 is a vitamin. It can be found in foods
such as meat, fish, and dairy products. It can also
be

made

Vitamin

B12

in
is

used

for

laboratory.
treating

and

preventing vitamin B12 deficiency, a condition in

which vitamin B12 levels in the blood are too low. It
is also used to treat perniciousanemia, a serious
type

of

anemia

that

is

due

to vitamin

B12

deficiency and is found mostly in older people. For

this purpose, people use either a supplement that is
taken by mouth or a gel that is applied inside the
nose.
Vitamin

B12

is

also

used

for memory

loss; Alzheimers disease; boosting mood, energy,

concentration and the immune system; and slowing
aging. It is also used forheart disease, lowering
high homocysteine levels (which may contribute
to heartdisease),
male infertility, diabetes, sleep disorders, depressio
n, mental disorders, weak bones (osteoporosis),
swollen

tendons,

AIDS, inflammatory

disease,asthma, allergies,

bowel

a skin disease

called vitiligo,
cancers,

preventing
and

cervical

and

skin

other

infections.

Some people use vitamin B12 for amyotrophic

lateral sclerosis (Lou Gehrigs disease), multiple
sclerosis,

preventing

related macular

the eye disease

age-

degeneration (AMD), Lyme

disease and gum disease. It is also used for ringing

in the ears, bleeding, liver and kidney disease, and
for protection against the poisons and allergens in
tobacco

smoke.

Vitamin B12 is applied to the skin either alone or in

combination

with

forpsoriasis and eczema.

avocado

oil

Vitamin B12 is frequently used in combination with

other B vitamins in various vitamin B complex
products.

How does it work?

Vitamin B12 is required for the proper function and
development of the brain, nerves, blood cells, and
many other parts of the body.

VITAMIN B12 USES & EFFECTIVENESS

Effective for:

Inherited Vitamin B12 deficiency (ImerslundGrasbeck disease). Injecting vitamin B12 as a

shot for 10 days followed by monthly injections for
the remainder of life is effective for treating
people with an inherited disease that results in
poor absorption of vitamin B12.

Pernicious anemia. Injecting vitamin B12 as a

shot, as well as taking through the nose or by
mouth, is effective for treating low red blood cell
counts caused by poor absorption of vitamin B12.

Vitamin B12 deficiency. Taking vitamin B12 by

mouth, through the nose, or as a shot is effective
for treating vitamin B12 deficiency.

Likely Effective for:

Cyanide

poisoning.

Administering

hydroxocobalamin (Cyanokit), a natural form of

vitamin B12, as a shot for a total dose of up to 10
grams is likely an effective treatment for cyanide
poisoning. Treatment of cyanide poising with
hydroxocobalamin (Cyanokit) has been approved
by the U.S. Food and Drug Administration (FDA).

High level of homocysteine in the blood

(Hyperhomocysteinemia). Taking vitamin B12 by

mouth, along with folic acid and sometimes

pyridoxine (vitamin B6), can lower blood levels of
homocysteine.

Possibly Effective for:

An eye disease called age-related macular

degeneration (AMD). Some research shows that
taking vitamin B12 with other vitamins, including
folic acid and vitamin B6, might help prevent an
eye

disease

degeneration.

called

age-related

macular

Possibly Ineffective for:

Sleep disorders. Taking vitamin B12 by mouth

does not seem to help people with sleep
disorders.

Mental function. Taking vitamin B12, alone or

in combination with folic acid and vitamin B6,
does not seem to improve memory, language, or
the ability to organize and plan in elderly people.

Stroke. Research suggests that people who

consume more vitamin B12 in their diet or those
who take vitamin B12 supplements do not have a
reduced risk of stroke or stroke reoccurrence.

Insufficient Evidence for:

Alzheimers disease. Early research suggests

that higher vitamin B12 intake does not seem to
prevent Alzheimers disease.

Preventing re-blockage of blood vessels after

heart

artery

dilation

(balloon

angioplasty).

Research is inconsistent about the benefits of

taking folic acid plus vitamin B6 and vitamin B12
following angioplasty. Some research suggests
that it might decrease the risk of re-blockage of
the blood vessels after balloon angioplasty.
However, it does not seem to benefit people who
had a tube (coronary stent) placed in the arteries.

Eczema (atopic dermatitis). Early research

shows

that

applying

vitamin

B12

cream

(Regividerm) to the affected area twice daily helps

treat eczema.

Breast cancer. There is no evidence that

dietary vitamin B12 alone reduces the risk of
breast cancer. However, vitamin B12 may reduce
the risk of breast cancer when taken with folate,
vitamin B6, and methionine.

Canker sores. Early research shows that

taking vitamin B12 1000 mcg under the tongue
(sublingually) might help reduce the number of
canker sore outbreaks, the duration of outbreaks,
and pain caused by the canker sores.

Cervical cancer. Early research suggests that

different forms of vitamin B12 taken together with
a thiamine derivative (benfotiamine) and vitamin
B6 might improve some symptoms of nerve pain
associated with diabetes.

Nerve damage caused by diabetes. Early

research suggests that different forms of vitamin
B12 taken together with a thiamine derivative
(benfotiamine) and vitamin B6 might improve
some symptoms of nerve pain associated with
diabetes.

Fatigue. There is some evidence that receiving

shots containing 5 mg of vitamin B12 twice

weekly might improve general well-being and

happiness in people with fatigue.

High

triglyceride

levels.

Some

evidence

suggest that taking 7.5 mcg of vitamin B12

together with 5 grams of fish oil might be more
effective then fish oil alone when used daily to
reduce total cholesterol and triglyceride levels.

Lung cancer. Early evidence suggests that

there is no relationship between levels of vitamin
B12 in the blood and the risk of lung cancer.

Psoriasis. Early research shows that a specific

cream containing vitamin B12 and avocado oil
(Regividerm, Regeneratio Pharma AG) reduces

symptoms of psoriasis as effectively as standard

care and causes less irritation.

Shaky-leg syndrome. There are some reports

that one form of vitamin B12 (cyanocobalamin)
can help reduce tremors due to shaky-leg
syndrome.

Allergies.

Aging.

Chronic fatigue syndrome (CFS).

Diabetes.

Heart disease.

Lyme disease.

Immune system problems.

Memory problems.

Multiple sclerosis.

Other conditions.
More evidence is needed to rate the effectiveness
of vitamin B12 for these uses.

VITAMIN B12 SIDE EFFECTS & SAFETY

Vitamin B12 is LIKELY SAFE for most people when
taken by mouth, applied to the skin, taken through
the

nose,

or

administered

as

shot..

Mild itching has been reported in one person who

used a specific avocado oil plus vitamin B12 cream
for psoriasis.

Special Precautions & Warnings:

Pregnancy
is LIKELY

and

breast-feeding:

SAFE for

pregnant

or

Vitamin

B12

breast-feeding

women when taken by mouth in the amounts

recommended.

The

recommended

amount

for

pregnant women is 2.6 mcg per day. Breast-feeding

women should take no more than 2.8 mcg per day.
Dont take larger amounts. The safety of larger
amounts

is

unknown.

High numbers of red blood cells (polycythemia

vera): The treatment of vitamin B12 deficiency can
unmask

the

symptoms

of

polycythemia

vera.

Abnormal red blood cells (megaloblastic anemia):

Megaloblastic anemia is sometimes corrected by

treatment with vitamin B12. However, this can have
very serious side effects. Dont attempt vitamin B12
therapy

without

healthcare

close

supervision

by

your

provider.

Lebers disease, a hereditary eye disease: Do not

take vitamin B12 if you have this disease. It can
seriously harm the optic nerve, which might lead to
blindness.
Allergy or sensitivity to cobalt or cobalamin: Do not
use vitamin B12 if you have this condition.
Post-surgical stent placement: Avoid using a

combination of vitamin B12, folate, and vitamin B6

after receiving a coronary stent. This combination
may increase the risk of blood vessel narrowing.

VITAMIN B12 DOSING

The following doses have been studied in scientific
research:
BY

MOUTH:

The typical general supplemental dose of vitamin

B12

is

1-25

mcg

per

day.

The recommended dietary allowances (RDAs) of

vitamin B12 are: Infants 0-6 months, 0.4 mcg;

infants 7-12 months, 0.5 mcg; children 1-3 years,
0.9 mcg; children 4-8 years, 1.2 mcg; children 9-13
years, 1.8 mcg; older children and adults, 2.4 mcg;
pregnant women, 2.6 mcg; and breast-feeding
women, 2.8 mcg. Because 10% to 30% of older
people do not absorb food-bound vitamin B12
efficiently, those over 50 years should meet the
RDA by eating foods fortified with B12 or by taking
a vitamin B12 supplement. Supplementation of 25100 mcg per day has been used to maintain
vitamin B12 levels in older people.

For vitamin B12 deficiency or pernicious

anemia: cyanocobalamin doses of 300-10,000

mcg (microgram) daily have been used. However,

some evidence suggests that the most effective
oral dose is between 647-1032 mcg/day.

For high blood levels of homocysteine: vitamin

B12 500 mcg in combination with 0.5-5 mg folic
acid and 16.5 mg pyridoxine has been used.

For

preventing

age-related

macular

degeneration (AMD): vitamin B12 1 mg, folic acid

2.5 mg, and pyridoxine 50 mg daily has been
studied.
APPLIED TO THE SKIN:

For atopic dermatitis (eczema): a specific

vitamin B12 0.07% cream (Regividerm) applied
twice daily has been used.

For psoriasis: a specific cream (Regividerm,

Regeneratio Pharma AG, Wuppertal, Germany)

containing avocado oil plus vitamin B12 0.7
mg/gram applied for 12 weeks twice daily has
been used.

Medical uses[edit]
Vitamin

B12 is

B12 deficiency, cyanide

used

to

treat vitamin

poisoning,

and hereditary

[10]

deficiency of transcobalamin II.

It is given as part

of the Schilling test for detecting pernicious anemia.

[10]

For cyanide poisoning,

large

amount

of

hydroxocobalamin may be given intravenously and

sometimes in combination withsodium thiosulfate.

[11]

The mechanism of action is straightforward: the

hydroxycobalamin hydroxide ligand is displaced by

the toxic cyanide ion, and the resulting harmless
B12 complex is excreted in urine. In the United
States, the Food and Drug Administration approved
(in 2006) the use of hydroxocobalamin for acute
treatment of cyanide poisoning.

[12]

High vitamin B12 level in elderly individuals may

protect

against brain atrophy or

shrinkage

associated with Alzheimer's disease and impaired

cognitive function.

[13]

Deficiency[edit]

Main article: Vitamin B12 deficiency

Vitamin B12 deficiency can potentially cause severe
and irreversible damage, especially to the brain and
nervous system. At levels only slightly lower than
normal,

range

of

symptoms

such

as fatigue, depression, and poor memory may be

experienced.

[2]

Vitamin B12 deficiency can also cause symptoms

[28][29]

of mania and psychosis.

Vitamin

B12

deficiency is most commonly caused by low

intakes, but can also result from malabsorption,
certain intestinal disorders, low presence of binding
proteins, and using of certain medications. Vitamin

B12 is rare from plant sources, so vegetarians will

be the vulnerable populations most likely to suffer
from vitamin B12 deficiency. Infants are at a higher
risk of vitamin B12 deficiency if they were born to
vegetarian mothers. The elderly who have diets
with limited meat or animal products are vulnerable
populations as well.

[30]

Vitamin B12 deficiency can

manifest itself as anemia and in some cases cause

permanent neurological damage. Recent studies
showed depression is associated with vitamin B12
deficiency;

sufficient

vitamin

B12

level

was

independently associated with a decreased risk of

depression

and

better

cognitive

performance

adjusted for confounders. Vitamin B12 is a cosubstrate of various cell reactions involved in

methylation

synthesis

of

nucleic

acid

and

neurotransmitters. Synthesis of the trimonoamine

neurotransmitters can enhance the effects of a
traditional

antidepressant.

[31]

The

intracellular

concentrations of vitamin B12 can be inferred

through

the

homocysteine,

total

plasma

which

can

concentration
be

converted

of
to

methionine through an enzymatic reaction that uses

5-methyletetrahydrofolate

as

the

methyl

donor

group. Consequently, the plasma concentration of

homocysteine falls as the intracellular concentration
of vitamin B12 rises. The active metabolite of
vitamin B12 is required for the methylation of
homocysteine in the production of methionine,
which is involved in a number of biochemical

processes

including

the

monoamine

neurotransmitters. Thus, a deficiency in vitamin B12

may impact the production and function of those
neurotransmitters.

[32]

Imerslund-Grsbeck syndrome is a rare disease

where

there

is

selective

malabsorption

of

cobalamine with proteinuria caused due to defect in

ileal receptor.

Sources[edit]

Foods[edit]
Ultimately, animals must obtain vitamin B12 directly
or indirectly from bacteria, and these bacteria may
inhabit a section of the gut that is distal to the
section

where

B12 is

Thus, herbivorous animals

must

absorbed.
either

obtain

B12 from bacteria in their rumens or (if fermenting

plant

material

in

the hindgut)

by

reingestion

of cecotrope feces.
Vitamin B12 is found in most animal derived foods,
including fish and shellfish, meat (especially liver),
poultry, eggs, milk, and milk products.

[2]

However,

the binding capacity of egg yolks and egg whites is

markedly diminished after heat treatment.

[33]

An NIH

Fact Sheet lists a variety of animal food sources of

B12.

[2]

Besides certain fermented foods,

[34][35]

there are

currently only a few non-animal food sources of

biologically

active

B12 suggested,

[citation

needed]

and

none of these have been subjected to human trials.

A

Japanese

fermented

as Batabata-cha has

been
[36]

biologically active B12.

made

by

fermenting

black
found

tea

known

to

contain

Unlike kombucha, which is

already

prepared

tea,

Batabata-cha is fermented while still in the tea leaf

state.

Chlorella,

[24][25][37]

a fresh-water single cell green

algae, has been suggested as a vitamin B12 source

but not proven by any live animal assay. Algae are

thought

to

acquire

B12through

symbiotic

relationship with heterotrophic bacteria, in which the

bacteria supply B12 in exchange for fixed carbon.
[39]

Spirulina and

dried

[38]

Asakusa-nori

(Porphyratenera) have been found to contain

mostly pseudovitamin-B12 (see Terminology) instead
of biologically active B12.

[8][9]

While Asakusa-nori

(Porphyra tenera) contains mostly pseudovitaminB12 in the dry state, it has been reported to contain
[9]

mostly biologically active B12 in the fresh state, but

even its fresh state vitamin activity has not been
verified by animal enzyme assay.

One group of researchers has reported that the

purple

laver

seaweed

(Pyropia yezoensis).

[26][27]

known

as

Susabi-nori

in its fresh state contains

B12 activity in the rat model, which implies that

source would be active in humans. These results
have not been confirmed.
A single commensal bacteria present in the gut of
many mammals has demonstrated an ability to
perform all steps necessary to synthesize B12 from
common metabolically available products.

[40]

Foods fortified with B12 are also sources of the

vitamin, although they cannot be regarded as true
food sources of B12 since the vitamin is added in
supplement

form,

from

commercial

bacterial

production

sources,

Examples

of

such

as

B12-fortified

fortified breakfast

cereals,

cyanocobalamin.
foods

include

fortified soy products,

fortified energy bars, and fortified nutritional yeast.

The UK Vegan Society, the Vegetarian Resource
Group,

and

the Physicians

Committee

for

Responsible Medicine, among others, recommend

that every vegan who is not consuming B12 foods
fortify with supplements.
contain

labeled

[41][22][23]

amounts

Not all of these may

of

vitamin

activity.

Supplemental B12 added to beverages in one study

was found to degrade to contain varying levels of
pseudovitamin-B12.

One

report

has

found

B12 analogues present in varying amounts in some

multivitamins.

[6][7]

Unconventional natural sources of B12 also exist,

but their utility as food sources of B12 are doubtful.
For example, plants pulled from the ground and not
washed may contain remnants of B12 from the
bacteria present in the surrounding soil.

[42]

B12 is

also found in lakes if the water has not been

sanitized.

[43]

Certain insects such

as termites contain

B12produced

by

their

gut

bacteria, in a way analogous to ruminant animals.

[44]

The human intestinal tract itself may contain B12-

producing bacteria in the small intestine,

[45]

but it is

unclear whether sufficient amounts of the vitamin

could be produced to meet nutritional needs.

Adverse effects[edit]

Hematologic:

Peripheral vascular

thrombosis has been

reported. Treatment of

vitamin B12 deficiency can unmask polycythemia

vera, which is characterized by an increase in
blood volume and the number of red blood cells.
The

correction

vitamin

of megaloblastic
B12 can

fatal hypokalemia and gout in

anemia with

result

in
susceptible

individuals, and it can obscure folate deficiency in

megaloblastic anemia.

Leber's disease: Vitamin B12 in the form of

cyanocobalamin

is contraindicated in

early Leber's disease, which is hereditary optic

nerve atrophy.

Cyanocobalamin

can

cause

severe and swift optic atrophy, but other forms of

vitamin B12 are available. However, the sources
of this statement are not clear, while an opposing
view

[57]

concludes: "The clinical picture of optic

neuropathy associated with vitamin B12 deficiency

shows similarity to that of Leber's disease optic
neuropathy. Both involve the nerve fibers of the
papillomacular bundle. The present case reports
suggest that optic neuropathy in patients carrying
a primary LHON mtDNA mutation may be
precipitated by vitamin B12deficiency. Therefore,
known carriers should take care to have an
adequate

dietary

intake

of

vitamin

B12 and

malabsorption syndromes like those occurring in

familial

pernicious

anaemia

or

after

gastric

surgery should be excluded."

Allergies[edit]
Vitamin

B12 supplements

in

theory

should

be

avoided in people sensitive or allergic to cobalamin,

cobalt, or any other product ingredients. However,
direct allergy to a vitamin or nutrient is extremely
rare, and if reported, other causes should be
sought.
Interactions[edit]

Alcohol (ethanol): Excessive alcohol intake

lasting longer than two weeks can decrease

vitamin B12 absorption from the gastrointestinal

tract.

[citation needed]

Aminosalicylic

acid (para-aminosalicylic

acid,

PAS, Paser): Aminosalicylic acid can reduce oral

vitamin B12 absorption, possibly by as much as
55%,

as

syndrome.

part

of

general

Megaloblastic

malabsorption

changes,

and

occasional cases of symptomatic anemia have

occurred, usually after doses of 8 to 12 g/day for
several months. Vitamin B12 levels should be
monitored in people taking aminosalicylic acid for
more than one month.

Antibiotics: An increased bacterial load can bind

significant amounts of vitamin B12 in the gut,

preventing its absorption. In people with bacterial

overgrowth of the small bowel, antibiotics such
as metronidazole (Flagyl) can actually improve
vitamin B12 status. The effects of most antibiotics
on gastrointestinal bacteria are unlikely to have
clinically significant effects on vitamin B12 levels.

Hormonal contraception: The data regarding the

effects

of

oral

contraceptives

on

vitamin

B12 serum levels are conflicting. Some studies

have

found

reduced

serum

levels

in

oral

contraceptive users, but others have found no

effect despite use of oral contraceptives for up to
6 months. When oral contraceptive use is
stopped,

normalization

of

vitamin

B12 levels

usually occurs. Lower vitamin B12 serum levels

seen with oral contraceptives probably are not
clinically significant.

Chloramphenicol (Chloromycetin): Limited case

reports suggest that chloramphenicol can delay
or

interrupt

the reticulocyte response

to

supplemental vitamin B12 in some patients. Blood

counts should

be

monitored

closely

if

this

combination cannot be avoided.

Cobalt irradiation: Cobalt irradiation of the small

bowel can

decrease

gastrointestinal

(GI)

absorption of vitamin B12.

Colchicine: Colchicine in doses of 1.9 to

3.9 mg/day can disrupt normal intestinal mucosal

function,

leading

to malabsorption of

several nutrients, including vitamin B12. Lower

doses do not seem to have a significant effect on
vitamin B12 absorption after 3 years of colchicine
therapy. The significance of this interaction is
unclear. Vitamin B12 levels should be monitored in
people taking large doses of colchicine for
prolonged periods.

Colestipol (Colestid), cholestyramine (Questran)

: These resins used for sequestering bile acids to
decrease cholesterol,

can

decrease

gastrointestinal (GI) absorption of vitamin B12. It is

unlikely this interaction will deplete body stores of
vitamin

B12 unless

there

are

other

factors

contributing to deficiency. In a group of children

treated with cholestyramine for up to 2.5 years,
there was not any change in serum vitamin
B12 levels.

Routine

supplements

are

not

necessary.

H2-receptor

antagonists:

include cimetidine (Tagamet), famotidine (Pepcid)

, nizatidine (Axid),
Reduced

and ranitidine (Zantac).

secretion

acid and pepsin produced

reduce

absorption

of

by

of gastric
H2 blockers

protein-bound

can

(dietary)

vitamin B12, but not of supplemental vitamin B12.

Gastric acid is needed to release vitamin B12 from
protein for absorption. Clinically significant vitamin

B12 deficiency and megaloblastic anemia are

unlikely, unless H2 blocker therapy is prolonged
(2 years or more), or the person's diet is poor. It
is

also

more

likely

if

the

person

is

rendered achlorhydric(with complete absence of

gastric

acid

secretion),

frequently with
H2 blockers.
monitored

occurs

proton pump inhibitors

Vitamin
in

which

people

B12 levels
taking

high

more
than

should
doses

be
of

H2 blockers for prolonged periods.

Metformin (Glucophage): Metformin may reduce

serum folic acid and vitamin B12 levels. Long-term
use of metformin substantially increases the risk
of B12 deficiency and (in those patients who

become deficient) hyperhomocysteinemia, which

is "an independent risk factor for cardiovascular
disease, especially among individuals with type
2diabetes."

[58]

There are also rare reports of

megaloblastic anemia in people who have taken

metformin for five years or more. Reduced serum
levels of vitamin B12 occur in up to 30% of people
taking

metformin

chronically.

[59][60]

However,

clinically significant deficiency is not likely to

develop

if

dietary

intake

of

vitamin

B12 is

adequate. Deficiency can be corrected with

vitamin B12 supplements even if metformin is
continued. The metformin-induced malabsorption
of vitamin B12 is reversible by oral calcium
supplementation.

[61]

The

general

clinical

significance of metformin upon B12 levels is as yet

unknown.

[62]

Neomycin: Absorption of vitamin B12 can be

reduced by neomycin, but prolonged use of large
doses is needed to induce pernicious anemia.
Supplements are not usually needed with normal
doses.

Nicotine: Nicotine can reduce serum vitamin

B12 levels.

The

need

for

vitamin

B12 supplementation in smokers has not been

adequately studied.

Nitrous oxide: Nitrous oxide inactivates the

cobalamin form of vitamin B12 by oxidation.
Symptoms

of

vitamin

B12 deficiency,

including sensory

neuropathy, myelopathy,

andencephalopathy, can occur within days or

weeks of exposure to nitrous oxide anesthesia in
people with subclinical vitamin B12 deficiency.
Symptoms are treated with high doses of vitamin
B12, but recovery can be slow and incomplete.
People with normal vitamin B12 levels have
sufficient vitamin B12 stores to make the effects of
nitrous oxide insignificant, unless exposure is
repeated and prolonged (such as recreational
use). Vitamin B12 levels should be checked in
people with risk factors for vitamin B12 deficiency
prior to using nitrous oxide anesthesia. Chronic
nitrous oxide B12 poisoning (usually from use of
nitrous oxide as a recreational drug), however,

may result in B12 functional deficiency even with

[63]

normal measured blood levels of B12.

Phenytoin (Dilantin), phenobarbital, primidone (

Mysoline):

These anticonvulsants have

been

associated with reduced vitamin B12 absorption,

and

reduced

serum

andcerebrospinal

fluidlevels in some patients. This may contribute

to the megaloblastic anemia, primarily caused by
folate deficiency, associated with these drugs. It
is also suggested that reduced vitamin B12 levels
may contribute to the neuropsychiatric side
effects of these drugs. Patients should be
encouraged to maintain adequate dietary vitamin

B12 intake. Folate and vitamin B12 status should

be checked if symptoms of anemia develop.

Proton

pump

inhibitors (PPIs):

The

PPIs

include omeprazole (Prilosec,

Losec), lansoprazole (Prevacid), rabeprazole (Aci
phex), pantoprazole (Protonix,
andesomeprazole (Nexium).

Pantoloc),
The

reduced

secretion of gastric acid and pepsin produced by

PPIs can reduce absorption of protein-bound
(dietary) vitamin B12, but not supplemental vitamin
B12. Gastric acid is needed to release vitamin
B12 from protein for absorption. Reduced vitamin
B12 levels may be more common with PPIs than
with H2-blockers, because they are more likely to

produce

achlorhydria

gastric

acid

significant

(complete

secretion).

vitamin

absence

However,

B12 deficiency

of

clinically

is

unlikely,

unless PPI therapy is prolonged (2 years or

more) or dietary vitamin intake is low. Vitamin
B12 levels should be monitored in people taking
high doses of PPIs for prolonged periods.

Zidovudine (AZT, Combivir, Retrovir): Reduced

serum

vitamin

B12 levels

may

occur

when

zidovudine therapy is started. This adds to other

factors that cause low vitamin B12levels in people
with HIV,

and

might

contribute

to

the

hematological toxicity associated with zidovudine.

However,

the

data

suggest

vitamin

B12 supplements are not helpful for people taking

zidovudine.

[citation needed]

Folic acid: Folic acid, particularly in large doses,

can mask vitamin B12 deficiency by completely
correcting hematological abnormalities. In vitamin
B12 deficiency, folic acid can produce complete
resolution

of

the

characteristic megaloblastic

anemia, while allowing potentially irreversible

neurological damage (from continued inactivity
of methylmalonyl mutase) to progress. Thus,
vitamin B12 status should be determined before
folic acid is given as monotherapy.

[64]

Potassium: Potassium supplements can reduce

absorption of vitamin B12 in some people. This

effect has been reported with potassium chloride

and, to a lesser extent, with potassium citrate.
Potassium

might

contribute

to

vitamin

B12 deficiency in some people with other risk

factors,

but

necessary.

routine

supplements

[65]

http://en.wikipedia.org/wiki/Vitamin_B12
http://en.wikipedia.org/wiki/Folic_acid

are

not