Saturday, December 23, 2006
Friday, December 22, 2006
MedWatch allows healthcare professionals and consumers to report serious problems that they suspect are associated with the drugs and medical devices they prescribe, dispense, or use. Reporting can be done on line, by phone, or by submitting the MedWatch 3500 form by mail or fax. Select How to Report for more details
Monday, December 18, 2006
*Cyanocobalamin* is a vitamin
commonly known as
*vitamin B12* DISCUSSION OF B12 ,MISCELANEOUS INFORMATION of INTEREST ...EXCERPTS FROM WIKIPEDIA and other sources
MOST EXPERTS WOULD AGREE THIS VITAMIN IS A NUTRIENT BUT ALSO A
" MEDICAL TREATMENT"FOR A VARIETY OF SERIOUS ILLNESSES
AND SHOULD BE DISCUSSED WITH PHYSICIAN.
THEREFORE THIS DISCUSSION SHOULD NOT BE USED FOR TREATMENT DECISIONS
.
The name *vitamin B12* is used in two different ways. In a broad sense it
refers to a group of cobalt -containing
compounds known as cobalamins - cyanocobalamin
the term B12 is used to refer to only one of
the forms, *cyanocobalamin*, which is the principal B 12 form used for
foods and in nutritional supplements.
*Pseudo-B12* refers to B12-like substances which are found in certain
organisms; however, these substances do not have B12 biological activity for
humans.B12 is the most chemically complex of all the vitamins. The structure
of B12is based on a corrin ring, which is similar to the porphyrin ring found in
heme ,chlorophyll , and cytochromes The central metal ion is Co cobalt .
Four of the six coordination sites are provided by the corrin ring, and a
fifth by a dimethylbenzimidazole group. The sixth coordination site, the
center of reactivity, is variable, being a
cyano a hydroxyl , a
methyl group (-CH3) or a 5'-deoxyadenosyl group
(here the C5' atom of the deoxyribose forms the covalent bond with Co),
respectively, to yield the four B 12 forms mentioned above. The covalent
C-Co bond is one of first examples of carbon-metal bonds in biology.
The hydrogenases
and, by necessity, enzymes
associated with CO utilization, involve metal-carbon
bonds
B12 cannot be made by plants or by
animals[
as the only type of organisms that have the enzymes required for the
synthesis of B 12 are bacteria and
archaea The total
synthesis of B
12 was reported in 1973 by Robert Burns
Woodward
Coenzyme B12's reactive C-Co bond participates in two types of
enzyme-catalyzed reactions.
1. Rearrangements in which a hydrogen atom is directly transferred
between two adjacent atoms with concomitant exchange of the second
substituent, X, which may be a carbon atom with substituents, an oxygen atom
of an alcochol, or an amine.
2. Methyl (-CH3) group transfers between two molecules.
In humans there are two coenzyme B12-dependent enzymes:
1. MUT Methylmalonyl_Coenzyme_A_mutase>which
uses the AdoB
12 form and reaction type 1 to catalyze a carbon skeleton
rearrangement (the X group is -COSCoA). MUT's reaction converts
MMl-CoA > -methylmalonyl-CoA an important step in the
extraction of energy from proteins and fats *(for more see MUT's
reaction mechanism
2. MTR 5-methyltetrahydrofolate-homocysteine_methyltransferase>,
a methyl transfer enzyme, which uses the MetB 12 and reaction type 2 to
catalyzes the conversion of the amino
acid Homocysteine> into
Met Methionine>
*(for more see MTR's reaction
mechanism -methyltetrahydrofolate-homocysteine_methyltransferase
History as a treatment for anemia
B12 DEFICIENCY is the cause of several forms of
anemia
The treatment for this disease was first devised by William
Murphy who
bled dogs to make them anemic and then fed them various substances to
see what (if anything) would make them healthy again discovered that
ingesting large amounts of liver seemed to cure the disease. George
Minot George_Richards_ and George
Whipple then set about to
chemically isolate the curative substance and ultimately were able to
isolate vitamin B12 from the liver. For this, all three shared the
1934 Nobel
Prize in Medicine and Nobel_Prize_in_Physiology
.
The chemical structure
of the molecule was
determined by Dorothy
Crowfoot Hodgkin nd
her team in 1956 , based on
crystallographic data.
>
The usual ADULT daily intake in the Western diet is 5–7
µg
Daily Value
the daily
requirement is 1–2 µg. B12 is mostly absorbed in the terminal
ileum
The production of intrinsic factor
in the
stomach is vital to absorption of
this vitamin. Megaloblastic
anemia can result from
inadequate intake of B12, inadequate production of intrinsic factor (pernicious
anemia disorders of the
terminal ileum resulting in malabsorption, or by competition for available B
12 by such as fish tapeworms or
bacteria present in" blind loop
syndrome"<
Hematological deficiency is manifested primarily by
anemia other cell lines
such as white blood cells and
platelets are often also low. Bone
marrow examination may show
megaloblastic
hemopoiesis Serum
homocysteine and
methylmalonic
acid
levels
are also high in B
12 deficiency and can be helpful if the diagnosis is unclear.
Neurological signs of B12 deficiency, which can occur without accompanying
hematologic abnormalities, include demyelination
and irreversible nerve cell
death. Symptoms include" numbness" or
"tingling" of the extremities and an "ataxic"UNSTEADY GAIT -INABILITY TO WALK
a syndrome known as subacute combined degeneration of the cord
The American Psychiatric
Association
*American Journal of Psychiatry* has published studies showing a
relationship between
depression levels and
deficient B
12 blood levels in elderly people i
Serum B12 levels are often low in B12 deficiency, but there does not exist a
robust assay, and if other features of B12 deficiency are present then the
diagnosis must not be discounted. One possible explanation for normal
B12 levels in B12 deficiency is? antibody interference in people with high titres of intrinsic
factor Bone marrow
aspiration, serum homocysteine and methylmalonic acid levels sometimes are part of the studies
Schilling_test can determine whether
symptoms of B12 deficiency are caused by lack of intrinsic factor
s
Vitamin B12 is naturally found in foods including meat (especially liver and
shellfish), eggs and
milk products. Fortified breakfast
cereals are a particularly
valuable source of vitamin B12 for
vegetarians
The only known vegan source of
substantial B 12, multivitamin
supplements
Interestingly, certain insects such as termites have been found to contain B
12.
Cyanocobalamin is also found in many energy
drinks
Vitamin B12 supplements should be avoided in people sensitive or
allergic to cobalamin, cobalt or
any other product ingredients.
warnings
- Cardiovascular: Caution should be used in patients undergoing
angioplasty since
intravenous loading dose of folic
acid
vitamin B6 and vitamin B12
followed by oral administration of folic acid 1.2mg plus vitamin B6
48mg and vitamin B12 60mcg taken daily after coronary
stenting Coronary_stenting might
increase restenosis rates? Due to the potential for harm this
combination of vitamins should not be recommended for patients receiving
coronary stents.
- Dermatologic: Itching Rash>,
transitory exanthema and
urticaria have been reported.
Vitamin B12 (20 micrograms/day) and
pyridoxine Pyridoxine>(80mg/day) have been
associated with cases of rosacea
fulminans characterized by
intense erythema(REDNESS) with
nodules
papules and
pustules
Symptoms may persist for up to 4 months after the supplement is stopped, and
may require
corticosteroids
- Gastrointestinal: Diarrhea
- Hematologic: Peripheral vascular
thrombosis
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.
In rare cases correction of megaloblastic
anemia with vitamin
B12 can result in FATAL
hypokalemia and
gout in susceptible individuals, and
it can OFTEN obscure folate deficiency in
megaloblastic anemia.
- Leber's disease: Vitamin B12 is contraindicated in early Leber's
disease which is
hereditary optic nerve Atrophy Vitamin B12 can cause
severe and swift optic atrophy in Lebers.
] Pregnancy and breastfeeding
Vitamin B12 in amounts that do not exceed
the recommended dietary allowance (RDA). The RDA for vitamin B12 in
pregnant women is
2.6mcg per day and 2.8mcg during
lactation
There is insufficient reliable information available about the safety of
consuming greater amounts of Vitamin B12 during pregnancy.
- Alcohol (ethanol Excessive
alcohol intake lasting longer than two weeks can DECREASE vitamin B12
absorption from the gastrointestinal tract
.
- Aminosalicylic
Aminosalicylic acid can REDUCE oral
vitamin B12 absorption, possibly by as much as 55%, as part of a general
malabsorption syndrome. Megaloblastic changes, and occasional cases of
symptomatic anemia have occurred, usually after doses of 8 to 12 grams/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,
. Vitamin B12 levels should be monitored in people
taking large doses of colchicine for prolonged periods
AS WELL AS MANY OTHER DRUGS NOT DISCUSSED IN THIS PRELIMINARY POSTING
Nicotine can
reduce serum vitamin B12 levels
Folic acid,
particularly in large doses, can mask vitamin B12 deficiency. In vitamin B12
deficiency, folic acid can produce hematologic improvement in megaloblastic
anemia, while allowing potentially irreversible neurological damage to
progress. Vitamin B12 status should be determined before folic acid is given
as monotherapy.
- 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 routine supplements are not
necessary.
SEE "Vitamin
B12
http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/
commonly known as
*vitamin B12* DISCUSSION OF B12 ,MISCELANEOUS INFORMATION of INTEREST ...EXCERPTS FROM WIKIPEDIA and other sources
MOST EXPERTS WOULD AGREE THIS VITAMIN IS A NUTRIENT BUT ALSO A
" MEDICAL TREATMENT"FOR A VARIETY OF SERIOUS ILLNESSES
AND SHOULD BE DISCUSSED WITH PHYSICIAN.
THEREFORE THIS DISCUSSION SHOULD NOT BE USED FOR TREATMENT DECISIONS
.
The name *vitamin B12* is used in two different ways. In a broad sense it
refers to a group of cobalt -containing
compounds known as cobalamins - cyanocobalamin
the term B12 is used to refer to only one of
the forms, *cyanocobalamin*, which is the principal B 12 form used for
foods and in nutritional supplements.
*Pseudo-B12* refers to B12-like substances which are found in certain
organisms; however, these substances do not have B12 biological activity for
humans.B12 is the most chemically complex of all the vitamins. The structure
of B12is based on a corrin ring, which is similar to the porphyrin ring found in
heme ,chlorophyll , and cytochromes The central metal ion is Co cobalt .
Four of the six coordination sites are provided by the corrin ring, and a
fifth by a dimethylbenzimidazole group. The sixth coordination site, the
center of reactivity, is variable, being a
cyano a hydroxyl , a
methyl group (-CH3) or a 5'-deoxyadenosyl group
(here the C5' atom of the deoxyribose forms the covalent bond with Co),
respectively, to yield the four B 12 forms mentioned above. The covalent
C-Co bond is one of first examples of carbon-metal bonds in biology.
The hydrogenases
and, by necessity, enzymes
associated with CO utilization, involve metal-carbon
bonds
B12 cannot be made by plants or by
animals[
as the only type of organisms that have the enzymes required for the
synthesis of B 12 are bacteria and
archaea The total
synthesis of B
12 was reported in 1973 by Robert Burns
Woodward
Coenzyme B12's reactive C-Co bond participates in two types of
enzyme-catalyzed reactions.
1. Rearrangements in which a hydrogen atom is directly transferred
between two adjacent atoms with concomitant exchange of the second
substituent, X, which may be a carbon atom with substituents, an oxygen atom
of an alcochol, or an amine.
2. Methyl (-CH3) group transfers between two molecules.
In humans there are two coenzyme B12-dependent enzymes:
1. MUT Methylmalonyl_Coenzyme_A_mutase>which
uses the AdoB
12 form and reaction type 1 to catalyze a carbon skeleton
rearrangement (the X group is -COSCoA). MUT's reaction converts
MMl-CoA > -methylmalonyl-CoA an important step in the
extraction of energy from proteins and fats *(for more see MUT's
reaction mechanism
2. MTR 5-methyltetrahydrofolate-homocysteine_methyltransferase>,
a methyl transfer enzyme, which uses the MetB 12 and reaction type 2 to
catalyzes the conversion of the amino
acid Homocysteine> into
Met Methionine>
*(for more see MTR's reaction
mechanism -methyltetrahydrofolate-homocysteine_methyltransferase
History as a treatment for anemia
B12 DEFICIENCY is the cause of several forms of
anemia
The treatment for this disease was first devised by William
Murphy who
bled dogs to make them anemic and then fed them various substances to
see what (if anything) would make them healthy again discovered that
ingesting large amounts of liver seemed to cure the disease. George
Minot George_Richards_ and George
Whipple then set about to
chemically isolate the curative substance and ultimately were able to
isolate vitamin B12 from the liver. For this, all three shared the
1934 Nobel
Prize in Medicine and Nobel_Prize_in_Physiology
.
The chemical structure
of the molecule was
determined by Dorothy
Crowfoot Hodgkin nd
her team in 1956 , based on
crystallographic data.
>
The usual ADULT daily intake in the Western diet is 5–7
µg
Daily Value
the daily
requirement is 1–2 µg. B12 is mostly absorbed in the terminal
ileum
The production of intrinsic factor
in the
stomach is vital to absorption of
this vitamin. Megaloblastic
anemia can result from
inadequate intake of B12, inadequate production of intrinsic factor (pernicious
anemia disorders of the
terminal ileum resulting in malabsorption, or by competition for available B
12 by such as fish tapeworms or
bacteria present in" blind loop
syndrome"<
Hematological deficiency is manifested primarily by
anemia other cell lines
such as white blood cells and
platelets are often also low. Bone
marrow examination may show
megaloblastic
hemopoiesis Serum
homocysteine and
methylmalonic
acid
levels
are also high in B
12 deficiency and can be helpful if the diagnosis is unclear.
Neurological signs of B12 deficiency, which can occur without accompanying
hematologic abnormalities, include demyelination
and irreversible nerve cell
death. Symptoms include" numbness" or
"tingling" of the extremities and an "ataxic"UNSTEADY GAIT -INABILITY TO WALK
a syndrome known as subacute combined degeneration of the cord
The American Psychiatric
Association
*American Journal of Psychiatry* has published studies showing a
relationship between
depression levels and
deficient B
12 blood levels in elderly people i
Serum B12 levels are often low in B12 deficiency, but there does not exist a
robust assay, and if other features of B12 deficiency are present then the
diagnosis must not be discounted. One possible explanation for normal
B12 levels in B12 deficiency is? antibody interference in people with high titres of intrinsic
factor Bone marrow
aspiration, serum homocysteine and methylmalonic acid levels sometimes are part of the studies
Schilling_test can determine whether
symptoms of B12 deficiency are caused by lack of intrinsic factor
s
Vitamin B12 is naturally found in foods including meat (especially liver and
shellfish), eggs and
milk products. Fortified breakfast
cereals are a particularly
valuable source of vitamin B12 for
vegetarians
The only known vegan source of
substantial B 12, multivitamin
supplements
Interestingly, certain insects such as termites have been found to contain B
12.
Cyanocobalamin is also found in many energy
drinks
Vitamin B12 supplements should be avoided in people sensitive or
allergic to cobalamin, cobalt or
any other product ingredients.
warnings
- Cardiovascular: Caution should be used in patients undergoing
angioplasty since
intravenous loading dose of folic
acid
vitamin B6 and vitamin B12
followed by oral administration of folic acid 1.2mg plus vitamin B6
48mg and vitamin B12 60mcg taken daily after coronary
stenting Coronary_stenting might
increase restenosis rates? Due to the potential for harm this
combination of vitamins should not be recommended for patients receiving
coronary stents.
- Dermatologic: Itching Rash>,
transitory exanthema and
urticaria have been reported.
Vitamin B12 (20 micrograms/day) and
pyridoxine Pyridoxine>(80mg/day) have been
associated with cases of rosacea
fulminans characterized by
intense erythema(REDNESS) with
nodules
papules and
pustules
Symptoms may persist for up to 4 months after the supplement is stopped, and
may require
corticosteroids
- Gastrointestinal: Diarrhea
- Hematologic: Peripheral vascular
thrombosis
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.
In rare cases correction of megaloblastic
anemia with vitamin
B12 can result in FATAL
hypokalemia and
gout in susceptible individuals, and
it can OFTEN obscure folate deficiency in
megaloblastic anemia.
- Leber's disease: Vitamin B12 is contraindicated in early Leber's
disease which is
hereditary optic nerve Atrophy Vitamin B12 can cause
severe and swift optic atrophy in Lebers.
] Pregnancy and breastfeeding
Vitamin B12 in amounts that do not exceed
the recommended dietary allowance (RDA). The RDA for vitamin B12 in
pregnant women is
2.6mcg per day and 2.8mcg during
lactation
There is insufficient reliable information available about the safety of
consuming greater amounts of Vitamin B12 during pregnancy.
- Alcohol (ethanol Excessive
alcohol intake lasting longer than two weeks can DECREASE vitamin B12
absorption from the gastrointestinal tract
.
- Aminosalicylic
Aminosalicylic acid can REDUCE oral
vitamin B12 absorption, possibly by as much as 55%, as part of a general
malabsorption syndrome. Megaloblastic changes, and occasional cases of
symptomatic anemia have occurred, usually after doses of 8 to 12 grams/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,
. Vitamin B12 levels should be monitored in people
taking large doses of colchicine for prolonged periods
AS WELL AS MANY OTHER DRUGS NOT DISCUSSED IN THIS PRELIMINARY POSTING
Nicotine can
reduce serum vitamin B12 levels
Folic acid,
particularly in large doses, can mask vitamin B12 deficiency. In vitamin B12
deficiency, folic acid can produce hematologic improvement in megaloblastic
anemia, while allowing potentially irreversible neurological damage to
progress. Vitamin B12 status should be determined before folic acid is given
as monotherapy.
- 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 routine supplements are not
necessary.
SEE "Vitamin
B12
http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/
Subscribe to:
Comments (Atom)
