Useful Facts About Cobalamin (vitamin B12)
Cobalamin (vitamin B12) is the largest B vitamin and was the
last one to be isolated in 1948 by Dr E. Lester Smith in the UK from
liver. It is a red crystalline substance. It had been known as early as
1926, that something in raw liver was a treatment for anaemia. There
are various forms of the cobalamin (so called due to the presence of
cobalt) molecule, some of these are; methyl-, cyano, adnosyl- and
hydroxocobalamin (B12b). There are also nitrit (B12c), sulphito and
aquacobalamins. The human body can normally convert from one to the
other. The human body typically contains 5000-10000 ?g of B12
distributed about equally between the liver, kidneys and nervous
system. Indeed the liver can store enough B12 for many years of supply,
so that daily ingestion of B12 is not required. Most of the B12 present
in animal tissues is in one of the two coenzyme forms, adnosylcobalamin
or methylcobalamin, and not actual vitamin B12 (cobalamin), which may
be present due to diffusion from gut bacteria or active transport using
intrinsic factor. Vitamin B12 is also water soluble and therefore
easily lost, whereas cobalamin coenzymes will remain in the liver and
nerve cells, and can be effectively recycled. B12 is now obtained by
deep fermentation. According to Leonard Mervyn, B.Sc., PH.D., C.Chem
F.R.S.C, in Thorsons Complete Guide to Vitamins & Minerals, pp42, 8
?g of B12 can be absorbed at any one time by the intrinsic factor and
calcium mechanism, only 1% being absorbed by simple diffusion following
oral dose. According to Mervyn, pig's liver contains 25.0?g/100g of
B12, therefore 100g of pigs liver will result in 8.017?g of B12
absorbed, assuming digestion is healthy.
Vitamin B12 is produced exclusively by microorganisms, but is also
found in animal flesh due to ingestion, or presence of the micro
organisms in the gut. However, since grazing "meat animals" tend to
accumulate heavy metals from the environment, it might be suggested
that animal sources of B12 are not as "good" a source as might be
supposed. Poultry, especially chickens, are routinely fed fishmeal,
which may contain significant amounts of mercury and other heavy
metals. Bottom feeding rather than deep sea fish contain the most
mercury. Vegans, by avoiding eating higher on the food chain, will
therefore accumulate less heavy metals (via diet) and may require far
less B12 as a result of that risk factor. We may therefore expect to
find a lower incidence of dementia, caused by heavy metal intoxication,
amongst amalgam free vegans.
B12 is a vitamin required for blood formation and rapidly growing
tissues. Methylcobalamin production requires cobalamin and is the
cobalamin found in the central nervous system (CNS) and brain where it
transports methyl groups (-CH3) to proteins in the myelin. It is for
these reasons that B12 deficiency leads to anaemia (blood disorders
include macrocytos and pernicious anaemia) and neurological disorders
(Alzheimer's disease and suspected amalgam related disorders). There
are, as with many diseases, usually more than one factor which may be
involved with causation. Given that the former disorders are rare, even
in vegans who have low B12 intakes, what I am more concerned about is
the potential for neurological disorders that may be subclinical. This
occurs because it is possible to have a deficiency of B12 in the CNS
even when blood levels of B12 are "normal", or what is called
non-anaemic deficiencies. These occur for meat eaters with huge B12
intakes as well as for vegans. So laying the blame for neurological
problems on veganism or indeed any alleged B12 intake deficiency is not
always accurate, since increased B12 dietary intake will evidently, not
always work. In these serious cases B12 is usually injected since
dietary availability of B12 can be as low as 1% of the total ingested
for mega B12 doses, and some patients do not convert dietary B12 to the
methylcobalamin required for normal neurological activity so well.
Symptoms could include: disturbed sense of co-ordination,
paraesthesiae, loss of memory, abnormal reflexes, weakness, loss of
muscle strength, exhaustion, confusion, low self-confidence,
spacticity, incontinence, impaired vision, abnormal gait, frequent need
to pass water and psychological deviances. Non-anaemic deficiencies
play a role in diseases such as Multiple Sclerosis, Fibromyalgia,
Diabetes and Chronic Fatigue Syndrome. Schizophrenia has also been
successfully treated with B12 plus other supplements, and
cardiovascular disease is linked to B12 deficiency while herpes zoster
used to be treated with B12 injections back in the 1950s.
Just as mercury may cause cobalamin deficiency in the nervous
system, so alcohol can cause deficiency in tissues. Even worse, alcohol
seems to raise serum levels of vitamin B12, so that the deficiency is
masked and the subject may look like they have higher than normal B12
levels! Whether these effects correlate to alcohol intake, or are only
found in "alcoholics" is not clear.
The Recommended Daily Allowances (RDAs) are (?g/day): 0.3 at age 0-6
months, 0.5 for 6-12 months, 0.7 for 1-3 years, 1.0 for 4-6 years, 1.4
for 7-10 years, 2.0 for adolescents and adults, 2.2 in pregnancy and
2.6 in lactation. Usual intakes are about 4-8 ?g/d. Pregnant,
lactating, and long-term strict vegetarians should take supplements
providing the RDA.
The stomach secretes intrinsic factor that binds B-12 and mediates
its absorption at receptor sites in the ileum. Inadequate intrinsic
factor secretion occurs in pernicious anemia, an autoimmune disease. In
the elderly, atrophic gastritis is commonly associated with B-12
malabsorption and deficiency. Because the absorbed vitamin is secreted
in bile and subsequently reabsorbed, deficiency symptoms can take 20
years to develop from low intakes, e.g., in strict vegetarians.
However, in malabsorption, deficiency occurs in months or a few years
because absorption from both the diet and enterohepatic circulation is
impaired.
The application of sensitive metabolic tests, such as the
deoxyuridine suppression test and measurement of homocysteine and
methylmalonic acid, to cobalamin status has identified the entity of
mild, preclinical cobalamin deficiency. This state, common in the
elderly, responds to cobalamin therapy. Preclinical deficiency may
exist within the nervous system as well, although this requires further
study. Nevertheless, it is well to remember that not all low cobalamin
levels and not all abnormal metabolite results reflect cobalamin
deficiency. Interpretation of metabolic results still requires caution,
as do proposals to raise the cut-off point for low cobalamin levels to
capture some normal levels that are associated with metabolic
abnormality. The recognition of mild, preclinical deficiency has opened
up many important issues. These include identifying its causes, what
should be done about it, and what the clinical impact of the
hyperhomocysteinemia itself is. Although malabsorptive disorders,
especially food-cobalamin malabsorption, underlie about half of all
cases of preclinical deficiency, no cause can be found in the remainder
of these cases; poor dietary intake appears to be uncommon. In
addition, unusual states of neurologically symptomatic cobalamin
deficiency are being recognized, such as nitrous oxide exposure in
patients with unrecognized deficiency and severe deficiency in children
of mildly deficient mothers. All of these have broadened and
complicated the picture of cobalamin deficiency while providing greater
opportunities for prevention.
Vitamin B12 deficiency associated neuropathy, originally called
subacute combined degeneration, is particularly common in the elderly.
The potential danger today is that with supplementation with folic acid
of dietary staples such as flour, that the incidenceof this disease
could rise as folic acid, as opposed to natural folate (N5CH3HFGlu1),
enters the cell and the metabolic cycle by a cobalamin independent
pathway. This chapter briefly describes the clinical presentation of
the disease, which unless treated will induce permanent CNS damage. The
biochemical basis of the interrelationship between folate and cobalamin
is the maintenance of two functions, nucleic acid synthesis and the
methylation reactions. The latter is particularly important in the
brain and relies especially on maintaining the concentration of
S-adenosylmethionine (SAM) which, in turn, maintains the methylation
reactions whose inhibition is considered to cause cobalamin deficiency
associated neuropathy. SAM mediated methylation reactions are inhibited
by its product S-adenosylhomocysteine (SAH). This occurs when cobalamin
is deficient and, as a result, methionine synthase is inhibited causing
a rise of both homocysteine and SAH. Other potential pathogenic
processes related to the toxic effects of homocysteine are direct
damage to the vascular endothelium and inhibition of
N-methyl-D-aspartate receptors.
Mild cobalamin deficiency is most common in elderly white men and
least common in black and Asian American women. Hyperhomocysteinemia,
which is most strongly associated with low cobalamin concentrations, is
also most common in elderly whites, whereas that associated with renal
insufficiency is more common in blacks and Asian Americans. Ethnic
differences in cobalamin deficiency and the homocysteine patterns
associated with it or with renal insufficiency warrant consideration in
supplementation strategies.
Cobalamin (vitamin B12) is the largest B vitamin and was the
last one to be isolated in 1948 by Dr E. Lester Smith in the UK from
liver. It is a red crystalline substance. It had been known as early as
1926, that something in raw liver was a treatment for anaemia. There
are various forms of the cobalamin (so called due to the presence of
cobalt) molecule, some of these are; methyl-, cyano, adnosyl- and
hydroxocobalamin (B12b). There are also nitrit (B12c), sulphito and
aquacobalamins. The human body can normally convert from one to the
other. The human body typically contains 5000-10000 ?g of B12
distributed about equally between the liver, kidneys and nervous
system. Indeed the liver can store enough B12 for many years of supply,
so that daily ingestion of B12 is not required. Most of the B12 present
in animal tissues is in one of the two coenzyme forms, adnosylcobalamin
or methylcobalamin, and not actual vitamin B12 (cobalamin), which may
be present due to diffusion from gut bacteria or active transport using
intrinsic factor. Vitamin B12 is also water soluble and therefore
easily lost, whereas cobalamin coenzymes will remain in the liver and
nerve cells, and can be effectively recycled. B12 is now obtained by
deep fermentation. According to Leonard Mervyn, B.Sc., PH.D., C.Chem
F.R.S.C, in Thorsons Complete Guide to Vitamins & Minerals, pp42, 8
?g of B12 can be absorbed at any one time by the intrinsic factor and
calcium mechanism, only 1% being absorbed by simple diffusion following
oral dose. According to Mervyn, pig's liver contains 25.0?g/100g of
B12, therefore 100g of pigs liver will result in 8.017?g of B12
absorbed, assuming digestion is healthy.
Vitamin B12 is produced exclusively by microorganisms, but is also
found in animal flesh due to ingestion, or presence of the micro
organisms in the gut. However, since grazing "meat animals" tend to
accumulate heavy metals from the environment, it might be suggested
that animal sources of B12 are not as "good" a source as might be
supposed. Poultry, especially chickens, are routinely fed fishmeal,
which may contain significant amounts of mercury and other heavy
metals. Bottom feeding rather than deep sea fish contain the most
mercury. Vegans, by avoiding eating higher on the food chain, will
therefore accumulate less heavy metals (via diet) and may require far
less B12 as a result of that risk factor. We may therefore expect to
find a lower incidence of dementia, caused by heavy metal intoxication,
amongst amalgam free vegans.
B12 is a vitamin required for blood formation and rapidly growing
tissues. Methylcobalamin production requires cobalamin and is the
cobalamin found in the central nervous system (CNS) and brain where it
transports methyl groups (-CH3) to proteins in the myelin. It is for
these reasons that B12 deficiency leads to anaemia (blood disorders
include macrocytos and pernicious anaemia) and neurological disorders
(Alzheimer's disease and suspected amalgam related disorders). There
are, as with many diseases, usually more than one factor which may be
involved with causation. Given that the former disorders are rare, even
in vegans who have low B12 intakes, what I am more concerned about is
the potential for neurological disorders that may be subclinical. This
occurs because it is possible to have a deficiency of B12 in the CNS
even when blood levels of B12 are "normal", or what is called
non-anaemic deficiencies. These occur for meat eaters with huge B12
intakes as well as for vegans. So laying the blame for neurological
problems on veganism or indeed any alleged B12 intake deficiency is not
always accurate, since increased B12 dietary intake will evidently, not
always work. In these serious cases B12 is usually injected since
dietary availability of B12 can be as low as 1% of the total ingested
for mega B12 doses, and some patients do not convert dietary B12 to the
methylcobalamin required for normal neurological activity so well.
Symptoms could include: disturbed sense of co-ordination,
paraesthesiae, loss of memory, abnormal reflexes, weakness, loss of
muscle strength, exhaustion, confusion, low self-confidence,
spacticity, incontinence, impaired vision, abnormal gait, frequent need
to pass water and psychological deviances. Non-anaemic deficiencies
play a role in diseases such as Multiple Sclerosis, Fibromyalgia,
Diabetes and Chronic Fatigue Syndrome. Schizophrenia has also been
successfully treated with B12 plus other supplements, and
cardiovascular disease is linked to B12 deficiency while herpes zoster
used to be treated with B12 injections back in the 1950s.
Just as mercury may cause cobalamin deficiency in the nervous
system, so alcohol can cause deficiency in tissues. Even worse, alcohol
seems to raise serum levels of vitamin B12, so that the deficiency is
masked and the subject may look like they have higher than normal B12
levels! Whether these effects correlate to alcohol intake, or are only
found in "alcoholics" is not clear.
The Recommended Daily Allowances (RDAs) are (?g/day): 0.3 at age 0-6
months, 0.5 for 6-12 months, 0.7 for 1-3 years, 1.0 for 4-6 years, 1.4
for 7-10 years, 2.0 for adolescents and adults, 2.2 in pregnancy and
2.6 in lactation. Usual intakes are about 4-8 ?g/d. Pregnant,
lactating, and long-term strict vegetarians should take supplements
providing the RDA.
The stomach secretes intrinsic factor that binds B-12 and mediates
its absorption at receptor sites in the ileum. Inadequate intrinsic
factor secretion occurs in pernicious anemia, an autoimmune disease. In
the elderly, atrophic gastritis is commonly associated with B-12
malabsorption and deficiency. Because the absorbed vitamin is secreted
in bile and subsequently reabsorbed, deficiency symptoms can take 20
years to develop from low intakes, e.g., in strict vegetarians.
However, in malabsorption, deficiency occurs in months or a few years
because absorption from both the diet and enterohepatic circulation is
impaired.
The application of sensitive metabolic tests, such as the
deoxyuridine suppression test and measurement of homocysteine and
methylmalonic acid, to cobalamin status has identified the entity of
mild, preclinical cobalamin deficiency. This state, common in the
elderly, responds to cobalamin therapy. Preclinical deficiency may
exist within the nervous system as well, although this requires further
study. Nevertheless, it is well to remember that not all low cobalamin
levels and not all abnormal metabolite results reflect cobalamin
deficiency. Interpretation of metabolic results still requires caution,
as do proposals to raise the cut-off point for low cobalamin levels to
capture some normal levels that are associated with metabolic
abnormality. The recognition of mild, preclinical deficiency has opened
up many important issues. These include identifying its causes, what
should be done about it, and what the clinical impact of the
hyperhomocysteinemia itself is. Although malabsorptive disorders,
especially food-cobalamin malabsorption, underlie about half of all
cases of preclinical deficiency, no cause can be found in the remainder
of these cases; poor dietary intake appears to be uncommon. In
addition, unusual states of neurologically symptomatic cobalamin
deficiency are being recognized, such as nitrous oxide exposure in
patients with unrecognized deficiency and severe deficiency in children
of mildly deficient mothers. All of these have broadened and
complicated the picture of cobalamin deficiency while providing greater
opportunities for prevention.
Vitamin B12 deficiency associated neuropathy, originally called
subacute combined degeneration, is particularly common in the elderly.
The potential danger today is that with supplementation with folic acid
of dietary staples such as flour, that the incidenceof this disease
could rise as folic acid, as opposed to natural folate (N5CH3HFGlu1),
enters the cell and the metabolic cycle by a cobalamin independent
pathway. This chapter briefly describes the clinical presentation of
the disease, which unless treated will induce permanent CNS damage. The
biochemical basis of the interrelationship between folate and cobalamin
is the maintenance of two functions, nucleic acid synthesis and the
methylation reactions. The latter is particularly important in the
brain and relies especially on maintaining the concentration of
S-adenosylmethionine (SAM) which, in turn, maintains the methylation
reactions whose inhibition is considered to cause cobalamin deficiency
associated neuropathy. SAM mediated methylation reactions are inhibited
by its product S-adenosylhomocysteine (SAH). This occurs when cobalamin
is deficient and, as a result, methionine synthase is inhibited causing
a rise of both homocysteine and SAH. Other potential pathogenic
processes related to the toxic effects of homocysteine are direct
damage to the vascular endothelium and inhibition of
N-methyl-D-aspartate receptors.
Mild cobalamin deficiency is most common in elderly white men and
least common in black and Asian American women. Hyperhomocysteinemia,
which is most strongly associated with low cobalamin concentrations, is
also most common in elderly whites, whereas that associated with renal
insufficiency is more common in blacks and Asian Americans. Ethnic
differences in cobalamin deficiency and the homocysteine patterns
associated with it or with renal insufficiency warrant consideration in
supplementation strategies.
- John Coleman. An Introduction To Cobalamin Metabolism-cobalamins: form, function, inhibitors, a vegan perspective
- Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med 2000;51:357-75
- Weir DG, Scott JM. Brain function in the elderly: role of vitamin B12 and folate. Br Med Bull 1999;55(3):669-82
- Ralph Carmel, Ralph Green, Et al. Serum cobalamin, homocysteine,
and methylmalonic acid concentrations in a multiethnic elderly
population: ethnic and sex differences in
cobalamin and metabolite abnormalities. merican Journal of Clinical
Nutrition, Vol. 70, No. 5, 904-910, November 1999
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