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Vitamin B12
:
Essential for Life
Vitamin B12 (cobalamin),
has a deep red colour and
is an important member of
the B group water soluble
vitamins. It has a key role
in the functioning of the
brain and nervous system, in
the production of energy in
mitochondria and
in the formation of red
blood cells. Severe lack of
vitamin B12 can
result in anaemia, whilst
even a moderate continued
lack has been associated
with several conditions
including neuritis, multiple
sclerosis, cognitive
impairment, dementia and
Alzheimer's disease.
Forms of vitamin B12
in the body
Vitamin
B12 has a central
cobalt atom (in pink on the
structure model), to which
are attached different
functional groups, which
lead to different forms (vitamers)
of the vitamin depending
upon the group. In the body
the two main forms of
vitamin B12 are
adenosylcobalamin (AdoCbl)
and methylcobalamin (MeCbl),
which are each used by a
different set of enzymes
within the cell. The
majority of injected vitamin
B12 preparations,
supplements, or food
additives have a synthetic
form of vitamin B12
called cyanocobalamin that
does not occur in nature.
Technically cyanocobalamin
is not a vitamin as it is
biologically inert and has
to be converted to the
active form in the body,
with the release of toxic
cyanide.
Adenosylcobalamin
is an essential co-factor
for the enzyme methylmalonyl
coenzyme A-mutase, which
functions in the catabolism
of isoleucine, valine,
threonine, methionine,
thymine, and odd-chain fatty
acids. Adenosylcobalamin
deficiency has been
associated with
mitochondrial dysfunction
and with inabiliity to use
odd chain fatty acids,
isoleucine, valine and
threonine as energy sources.
Methylcobalamin
is the
specific vitamin B12 form
used by 5-methyltetrahydrofolate-homocysteine
methyltransferase (MTR),
also known as methionine
synthase. The enzyme is
required to transfer the
methyl group from
methylcobalamin to
homocysteine, thereby
forming methionine, which is
a precursor in the
production of
S-adenosylmethionine (SAM),
and essential methyl donor
in the cell (see the section
on MTHFR). Deficiency of
methylcobalamin is
associated with reduced
methylation, low
intracellular glutathione
levels.
Absorption of
Vitamin B12
Absorption of vitamin B12
from the intestine requires
that it be released from
food through the action of
various enzymes in the
intestine. It then must be
bound by a specific
transport protein, called
intrinsic factor which is
released in the stomach. Patients
who are deficient in
intrinsic factor, or who
have antibodies against intrinsic
factor can become deficient in
vitamin B12.
which may eventually lead to
pernicious anaemia. The capacity of the vitamin
B12- intrinsic
factor mediated uptake is
very limited and in humans
it is only possible to
absorb 1-1.5 ug of vitamin B12
per feed.
Absorption of vitamin B12
can be severely impaired in patients
who have intrinsic factor
deficiency or who may gastro-intestinal
problems, such as gastric
ulcers, atrophic gastritis,
Crohn’s
Disease and Ulcerative
Colitis. Vitamin B12
deficiency can also be a
result of various
intestinal
parasites/bacteria including
H. pylori
infections, Giardia
lamblia, and
bacterial overload. Once the
vitamin B12 has
been absorbed from the
intestine it is removed from
intrinsic factor and
transferred to
transcobalamin (TCII).
Vitamin B12 must
be bound to transcobalamin
II to be taken up by the
majority of cells in the
body.
Vitamin B12
Deficiency
Vitamin B12
deficiency is arguably the
most under-diagnosed
condition in the community.
"In general, doctors are
trained to recognize only
the blood abnormalities
associated with B12
deficiency - macrocytosis. B12
deficiency, however, mimics
many other diseases and
often physicians fail to
confirm B12
deficiency and therefore
fail to test for it. The
development of vitamin B12
deficiency is a slow and
insidious process, which may
take several years to
manifest itself. During this
time there can be
progressive loss of vitamin
B12 in the
cerebrospinal fluid (CSF),
which precedes overt
deficiency as measured in
serum, and without anaemia
or macrocytosis. Deficiency of the
vitamin in the CSF can lead
to brain atrophy
(shrinkage) and
subacute combined
degeneration of the
spinal cord, cerebrovascular
disease, Parkinson's
disease, dementia,
Alzheimer's' disease,
multiple sclerosis.
Vitamin B12
deficiency in the elderly
has been associated with
an unstable gait,
numbness and tingling in the
hands and feet, urinary incontinence, hearing loss
and an increased incidence
of bone fracture.
Vitamin B12
deficiency in pregnant
mothers is associated with
an increased incidence of
neural tube defects in the
young and the development of
Autism in the new
born. Apart from the
conditions mentioned above
deficiency in either vitamin
B12 or folate
often leads to
hyperhomocystinaemia, which
has been associated with MS,
AD, dementia, cardiovascular
disease and many other
conditions. Once
a person is deficient in
vitamin B12, it
is almost impossible to overcome
this deficient through
dietary supplementation,
particularly if the
underlying cause is not
removed/cured. Thus persons who are
deficient normally require
regular injections of vitamin B12,
Recently it has been found
that it is possible to
obtain vitamin B12
through application to the
skin using specialized
topical technology described
in this site. Vitamin
B12 deficiency can be
further exacerbated in the
presence of
MTHFR genetic mutations.
Vitamin B12
deficiency (<150 ρmol/L) is
associated with cognitive
impairment.
Low
vitamin B12
levels have also been
associated with multiple
sclerosis,.
Pregnant women with vitamin
B12 levels below 250 pmol/L
have twice the incidence of
children with neural tube
defects than those with
higher levels.
Post menopausal women with
low levels of vitamin B12
have been shown to have a
higher risk of breast cancer
(see
http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/
)
Causes of
Vitamin B12
Deficiency
Vitamin B12
deficiency can occur
after bowel resection, or
gastric by-pass surgery.
Vitamin B12
deficiency can occur due to
atrophic gastritis, a
condition that effects
10-30% of the elderly. Other causes of vitamin B12
deficiency include
achlorhydria, ageing,
excessive antibiotics or
anti-convulsants (often used
in persons with epilepsy),
gastrectomy, especially of
the cardiac or fundus, liver
disease or cancer,
megadoses of vitamin C
and/or copper, pregnancy,
intestinal parasites such as
Giardia, fish
tapeworms, a primarily vegan
or vegetarian
diet, certain religions,
such as 7th Day Adventists,
Rastafarians, and excessive
smoking.
Vitamin B12
deficiency has also been
associated with the use of
the following drugs,
cholestyramine, cymetidine,
clofibrate, colchicine,
Isotretinoin (Accutane), methotrexate, methyldopa,
neomycin, omeprazole, some
oral contraceptives, phenobarbital, ranitidine,
tetracyclines, valproic acid,
anti-epileptic drugs (carbamazipine
and others)
and zidovudine (AZT).
Vitamin B12
deficiency can be a serious
complication of
Metformin use in
people with diabetes.
Hypothyroidism is
often also associated with
vitamin B12
deficiency
Individuals
with hypothyroidism have a
reduced capacity to convert
riboflavin (vitamin B2) to
flavin mononucleotide (FMN)
or flavin adenine
dinucleotide (FAD).
This then results in the
reduced capacity to recycle
folate leading to
"sacrificial" use of methyl
cobalamin for the
methylation cycle,
ultimately leading to
vitamin B12 deficiency (see
the section on
VB12
and MTHFR).
Dietary insufficiency of
folate can reduce the
ability to regenerate methyl
B12, thereby
causing vitamin B12
deficiency. Dietary
insufficiency of iodine,
selenium and/or molybdenum
can lead to functional
vitamin B2 deficiency, due
to their role in converting
dietary vitamin B2
(riboflavin), into the two
active forms of the vitamin,
flavin mononucleotide (FMN)
and flavin adenine
dinucleotide (FAD). The
result is very similar to
the effect of
hypothyroidism, and
supplementation with one or
all of these metals is
required to overcome the
deficiency, even in the
presence of adequate vitamin
B2 (riboflavin) intake.
Mutations in the genes for
several enzymes involved in
the folate cycle and
methylation can also lead to
vitamin B12 deficiency (vzi
MTHFR, MTR, MTRR, amongst
others) and also in
inherited genes involved in
the proteins involved in
vitamin B12 processing
within the cell (cblA, B, C,
D, E, F).
Vitamin B12
-
Definition of Deficiency -
levels in serum
In the USA and Australia, normal levels of vitamin B12
have been determined to be
in the range 180-750 pmol/L
(244-1017 pg/ml), with
vegans normally much lower
at around 110 pmol/L, being
regarded as deficient.
Recently, many studies
looking at biological
markers of vitamin B12
deficiency (MMA and Hcy) as
well as neurological markers
of deficiency, have suggested
that deficiency may start at
300 pmol/L (406 pg/ml), which is also
regarded as the lower level
of the normal range by the
Japanese health authority. It
is estimated that as many as
two thirds of the people who
are in the lower range of
serum vitamin B12
levels (190-300 pmol/L) may
have functional vitamin B12
deficiency (see
PDF), thus the true
level of vitamin B12
deficiency may be as high as
14-40%, depending upon the
population.
Subclinical deficiency in
vitamin B12 (<250 pmol/L) can
be monitored by rises in the
level of homocysteine (Hcy)
(>10 umol/L) and methylmalonic
acid (>200 noml/L).
Increased levels of Hcy is
associated with vascular
inflammatory disease and increases in
cardiovascular disease,
whilst increases in MMA can
result in destruction of the
myelin sheath around
neurones.
One of the problems with the
measurement of vitamin B12
in serum is that current
methods do not determine
which analogue(s) is(are)
present. Thus, if a subject
has been injected with
cyanocobalamin and then
serum vitamin B12 is
measured, the subsequent
measurement, which shows
increased vitamin B12
really only establishes that
the injection has been
successful. It does not
"tell" you if the
cyanocobalamin (CN-B12) has
been converted to methyl or
adenosyl B12.
More recently a new test,
called the Active B12
test, has been added to
the list of tests,
pertaining to measure levels
of vitamin B12 in
serum. This test is poorly
named, as the test measures
the amount of vitamin B12
(of unknown identity) that
is bound to transcobalamin
II (the vitamin B12
carrier responsible for
uptake into the cell). Once
again it does not determine
if in fact the subject has
the active forms of vitamin
B12 (adenosyl and
methyl B12), and
as such has very
questionable utility.
Unfortunately this aspect of
the test is not stated on
the general Information
Sheets for the test.
Symptoms of
Vitamin B12
Deficiency
Vitamin B12
deficiency can result in the
following conditions
-
Ataxia (poor muscle
do-ordination),
-
pernicious anemia,
-
Confusion,
-
Depression,
-
Disorientation, psychoses,
schizophrenia, ADHD
-
Fatigue, being
easily tired
-
Glossitis, impaired
lymphocyte response,
-
Memory
loss,
dementia, cognitive decline,
brain fog
-
Decreased libido,
low sperm count, erectile dysfunction, low
testosterone,
-
increased rate of
miscarriage in women,
,
-
Paresthesia (tingling of
fingers, toes, arms, legs,
etc),
-
Progressive
peripheral
neuropathy with pronounced anemia,
-
Spinal
degeneration,
-
Brain atrophy,
and macrocytic cells.
-
Increased
incidence of canker sores.
-
Alzheimer's disease
-
Vascular dementia, and
-
Parkinson's disease
-
Insomnia, or trouble
sleeping through the night
-
Food intolerance,
particularly to sulfites
-
Incontinence of bowel or
bladder, including "having
to get up during the night".
-
Irregular or poor control of
blood pressure, and
irregular breathing patterns
-
Itchy skin.
-
Inability to lose weight.
Why vitamin B12 levels in serum
may be misleading
The methods used for
measurement of vitamin B12
levels in serum do not
determine what form of
vitamin B12 is present in
the serum, nor what the
vitamin B12 is bound to.
Thus, in individuals
supplementing with high
doses of vitamin B12, the
subsequent measurement of
vitamin B12 is generally a
reflection of the analogue
of vitamin B12 used in the
supplements. Thus, if
cyanocobalamin (the inactive
vitamer) has been used in
supplementation, this is the
form measured, Similarly for
hydroxycobalamin
Similarly the generally used
detection methods do not
distinguish if the vitamin
B12 (of whatever form) is
free, or bound to
transcobalamin II (the form
required for uptake into the
cell) or to haptocorrin (the
form that is unavailable to
the cell). Care must
therefore be taken in
assuming that just because
vitamin B12 levels have been
increased or are high in
serum the vitamin B12 may
either not be bound to
transcobalamin II, or it is
not the active forms,
adenosyl or methylcobalamin.
Therapeutic use of
Vitamin B12
Vitamin
B12 has been used
in therapy for many
conditions including
AIDS/HIV support, anaemia,
anaemia of pregnancy,
pernicious anaemia, asthma,
atherosclerosis, allergies, atopic
dermatitis, contact
dermatitis, psoriasis,
seborrheic dermatitis, bursitis, sciatica,
canker
sores, chronic fatigue
syndrome, Alzheimer’s disease,
dementia, depression, Crohn’s disease,
diabetes
mellitus, diabetic
neuropathies, neuralgias, post-herpetic neuralgia,
diabetic
retinopathy, fatigue,
herpes zoster, high
cholesterol, high
blood homocysteine
levels, insomnia, male
infertility,
tinnitus, viral hepatitis,
and vitiligo. Recent studies
have shown that high dose
vitamin B12
treatment can slow or
prevent brain shrinkage and
loss of cognitive
impairment. High dose
formulations have also been
shown to reverse bowel and
bladder incontinence.
Prevention of
Vitamin
B12
Deficiency
Vitamin
B12 insufficiency
can be prevented either by
adherence to a diet that is
sufficient in vitamin B12
(see link), by the use of
supplements, by injection of
vitamin B12 or
via topical administration
of vitamin B12.
Persons who are deficient
due to poor absorption, or
through conditions affecting
absorption require regular
vitamin B12
supplementation either via
vitamin B12
injections or by
regular application of
topical vitamin B12.
Overcoming
Vitamin
B12
Deficiency
Unfortunately it is almost
impossible to to overcome
deficiency once it occurs,
through either a change in
diet or by the use of
standard supplements. The
normal uptake system in the
gut for vitamin B12 is not
sufficient to deliver enough
vitamin B12 to overcome
deficiency, a situation made
even worse in those who have
compromised intestinal
uptake, are on various drugs
or take metformin. Prompt
treatment of B12
deficient patients is
required to prevent
progressive, irreversible
neurological and cognitive
impairment. In addition,
measurement of serum vitamin
B12 levels may not be
indicative of deficiency in
the central nervous system
(CNS), particularly during
periods of vitamin B12
supplementation, where it
may be possible to
significantly boost serum
levels of vitamin B12,
however, levels in the CNS
may be relatively unchanged,
or only slightly increased.
Vitamin
B12 in
Supplements
The use
of vitamin B12
in supplements for
treatment of deficiency is
controversial with many
studies showing no benefit
being obtained from standard
supplements as the amount of
vitamin B12 in
the standard supplements is
too low, and because almost
invariably the supplement
contains cyanocobalamin (a
synthetic pro-vitamin)
rather than
adenosylcobalamin or
methylcobalamin, the two
natural forms of the
vitamin. Furthermore,
studies with high dose oral
supplements with
cyanocobalamin were not
effective in restoring
normal levels of
homocysteine or
methylmalonic acid, in reversing
clinical signs of
deficiency, or in
maintaining normal levels of
serum vitamin B12 once
supplements were ceased. In
addition, high dose oral
supplements have NOT been
shown to be able to increase
the concentration of vitamin
B12 in the
cerebral spinal fluid, or
the brain. Furthermore, in
inflammatory conditions
where there are high
circulating levels of
homocysteine, vitamin B12
introduced by supplements is
quickly inactivated to form
homocysteinyl-vitamin B12.
Vitamin
B12 Injections
Vitamin B12
injections can be
administered in cases of
insufficiency, however these
are generally expensive,
must be given by a medical
practitioner, are painful
and like oral supplements,
invariably contain
cyanocobalamin (a synthetic
pro-vitamin) rather than
adenosylcobalamin or
methylcobalamin, the two
natural forms of the
vitamin. In some countries
such as Europe and South
America both the methyl and adenosyl-vitamin B12
forms of the vitamin are
available for injection.
Injections must be given
every 4 to 6 weeks, as they
do not seem to overcome
deficiency, but merely
provide a
temporarily boost in
circulating levels of
vitamin B12
Topical
Vitamin B12
A
topical form of
vitamin B12
has recently been developed. This
preparation
is easy to administer,
contains the natural form of
the vitamin, is able to
deliver therapeutic amount
of vitamin B12
and has the
added advantage of providing
a prolonged release of the
vitamin over several days.
This prolonged release
potentially allows for
continuous loading of the
various organs including the
liver and more importantly
the CNS and brain. Moreover,
the high dose of vitamin B12
that is deliverable by this
method is sufficient to act
as a powerful anti-oxidant
and also to neutralize
circulating levels of
homocysteine, thus reducing
the incidence and severity
of conditions associated
with hyperhomocystinaemia.
This is not possible with
the much lower dose of
vitamin B12 that
is delivered via
supplements. See
ContactB12Oils
Further
Information on Vitamin B12
and its uses
Further information on
vitamin B12 and
deficiency states, as well
as potential use of vitamin
B12 can found by
following the links.
http://www.abc.net.au/radionational/programs/healthreport/vitamin-b12-supplementation-and-ageing/5031170
http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
NIHPDF
http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/
http://blogs.psychcentral.com/therapy-soup/2013/02/could-vitamin-b12-help-your-anxiety-depression/
http://www.nrv.gov.au/nutrients/vitamin%20b12.htm
http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/
http://www.abc.net.au/radionational/programs/healthreport/vitamin-b12-supplementation/3823160#transcript
PDF
http://www.youtube.com/watch?feature=player_embedded&v=BvEizypoyO0
www.B12D.org :
www.B12.com :
www.vitaminb12deficiency.net.au
http://b12awareness.org/
Pacholok, S.M. and Stuart,
J. J. Could it be B12? An
epidemic of misdiagnosis.
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