Supplemental vitamin B12 is used primarily to ensure
sufficient cyanocobalamin intake. It is used in ameliorating various
clinical conditions, including elevated plasma homocysteine, AIDS,
impaired mental function in the elderly, asthma and sulfite sensitivity,
depression, diabetic neuropathy, low sperm count, multiple sclerosis, and
tinnitus.(1)
Vitamin B12 is the common name of cobalamine, which is a
tetrapyrrole structure that chelates an atom of cobalt in the center of
the structure. Its active forms in the body are methylcobalamin and
deoxyadenosylcobalamin, both are essential cofactors for two enzymes of
intracellular metabolism, with the methyl form attaching to methionine
synthase and the adenosyl form attaching to methymalonyl CoA mutase.(5)
Cobalamin is synthesized only by animal gut bacteria, but is distributed
throughout all forms of animal tissue, with the liver being the cite of
highest concentration. Thus, it is not found in plants, predisposing vegan
vegetarians to potential B12 deficiency.
Methymalonyl CoA mutase facilitates the conversion of propionic
acid to succinic acid, which is essential to fatty acid metabolism.(5) A
high level of methylmalonic acid (MMA) is associated with low levels of
available cobalamin, and is usually accepted as diagnostic of cobalamin
deficiency.(1,5)
Methionine synthase mediates two crucial intracellular metabolic
processes, the synthesis of nucleic acid, which controls growth and
cellular division, and secondly, the numerous methylation reactions.
Deficiency of cobalamin leads to two well recognized clinical
manifestations, pernicious anemia, also called megaloblastic anemia
because the red blood cells are larger than normal, and to
cobalamin-associated neuropathy in which the spinal cord, brain, optic
nerve and peripheral nerves may be affected.(5,6)
An important manifestation of B12 deficiency, and the failed
methylation that B12 deficiency brings, is the elevation of plasma
homocysteine. Elevated plasma homocysteine is now viewed by many experts
as a greater risk factor than elevated cholesterol for developing coronary
heart disease.(9) Homocysteine must be methylated to form methionine via
B12 or folic acid, or converted to cysteine via vitamin B6. Homocysteine
is a natural cellular by-product of methionine metabolism, intended to
have a transient existence. Failure to metabolize homocysteine to
methionine or cysteine leads to unresolved elevated plasma levels.
Homocysteine is cytotoxic to the endothelium and is able to initiate the
focal lesions that will become coronary atherosclerosis.(9)
Absorption of vitamin B12 is aided by a gastric intrinsic factor.
However, even in the absence of this intrinsic factor, passive absorption
of an oral dose is possible, but higher than normal daily doses are
required.(1) The current practice is to use injectable cobalamin, and this
may be the most judicious initial approach. However, early studies have
demonstrated that pernicious anemia, secondary to an inability to
synthesize the gastric intrinsic factor, could be controlled with a B12
dosage range of 300 to 1000 mcg per day.(1) One of the most impressive was
a three year Swedish study with 64 patients with pernicious anemia and
other cobalamin-related pathologies. The patients were treated with 1000
mcg of cobalamine orally. At the end of the study, the patients
demonstrated complete normalization of blood levels and liver storage of
cobalamine, and complete clinical remission.(1,10,11)
Absorption may also be diminished simply as a result of growing
older, even when some measure of intrinsic factor is present.(9) This is
likely to be an important reason in explaining why a significant number of
the elder population demonstrate low plasma B12 levels. Older patients at
the pharmacy should be encouraged to have their physician assess their B12
status.
Vitamin B12 deficiency can occur over time in strict
vegetarians.(2)
Under the right circumstances, supplementing folic acid can mask vitamin
B12 depletion.
Normally folic acid is recycled as a methyl donor by being reactivated by
vitamin B12, acting itself as a methyl donor to folic acid. When tissue
folic acid levels are low, a co-existing vitamin B12 deficiency will be
manifested through even greater failure of folic acid metabolism,
ultimately leading to pernicious anemia. However, persistent vitamin B12
depletion also leads to neurological damage.
The concern is that new daily supplemented folic acid can
overcome the metabolic problems that lead to pernicious anemia without
averting neurological damage. Because the neurological damage evolves
slowly, supplementing folic acid without also supplementing B12 can mask a
true B12 depletion allowing neurological damage to proceed unsuspected. It
is always recommended that folic acid and vitamin B12 be supplemented
together.
Impaired neurological function in the elder population
due to vitamin B12 depletion can be an important but unsuspected factor
when there is not also evidence of anemia. Many physicians fail to
investigate vitamin B12 depletion if there is not also evidence of anemia,
yet two of the most depleted nutrients in the elder population are vitamin
B12 and folic acid.(1) In all cases of impaired mental function or
depression vitamin B12 status should be determined and treated
accordingly.(3,4)
Vitamin B12, folic acid, and vitamin B6 have a
recognized interactive relationship.
Absorption or utilization of
vitamins B12 and B6 is affected by regular alcohol intake.(7) Methotrexate
adversely affects the intestinal mucosa so that vitamin B12 and folic acid
are not absorbed well. It may be necessary to enhance supplementation of
B12 and folic acid.(7)
Oral contraceptives interfere with the absorption of folic acid and
vitamin B6. Since these nutrients are interactive with vitamin B12,
long-term use of OC's may impact metabolism that is controlled by these
nutrients.(7) Vitamin B12 absorption might be interfered by
colchicine.(7) Corticosteroids used long-term can deplete the body of
vitamins B6, B12, and folic acid.(7) Tranquillizers may deplete vitamin
B12.(7)
Potassium supplements can interfere with vitamin B12 absorption. Because
potassium supplementation can be required for life, B12 depletion can be a
meaningful risk. The older age group typically associated with potassium
supplements is also associated with low plasma B12
levels.(5,7)
Para-aminosalicylate may deplete both vitamin B12 and
folic acid.(7) Cimetidine, Ranitidine, omeprazole, and possibly other acid
suppressing drugs can reduce absorption of vitamin B12.(7) Zidovudine
(Retrovir or AZT) may interfere with the absorption of vitamin B12.
Metformin can interfere with the absorption of vitamin B12 and folic acid.
(CPS)
1. Murray, Michael T., Encyclopedia of Nutritional
Supplements, Prima Publishing, Rocklin, CA, 1996
2. Chanarin, Israel, Nutritional Aspects of Hematologic Disorders, in
Modern Nutrition in Health and Disease, eds., Maurice E. Shils, James A.
Olson, Moshe Shike, A. Catharine Ross, ninth edition, Lippincott Williams
& Wilkins, New York, 1999
3. Van Goor, et al, Review, Cobalamine deficiency and mental impairment in
elderly people, Age Ageing, 24: 536-542, 1995
4. Shevell, M.I., and D.S. Rosenblatt, The neurology of cobalamine, Can J
Neurol Sci, 19:472-486, 1992
5. Weir, Donald G. and John M. Scott, Vitamin B12 "Cobalamin", in Modern
Nutrition in Health and Disease, eds., Maurice E. Shils, James A. Olson,
Moshe Shike, A. Catharine Ross, ninth edition, Lippincott Williams &
Wilkins, New York, 1999
6. Jeffery, Douglas R., Nutrition and Diseases of the Nervous System, in
Modern Nutrition in Health and Disease, eds., Maurice E. Shils, James A.
Olson, Moshe Shike, A. Catharine Ross, ninth edition, Lippincott Williams
& Wilkins, New York, 1999
7. Graedon, Joe, Teresa Graedon, Deadly Drug Interactions, St Martin's
Griffin, New York, 1995
8. Palteil, O., et al, Clinical correlates of subnormal vitamin B12 levels
in patients infected with the human immunodeficiency virus, Am J Hematol,
49:318-322, 1995
9. McCully, Kilmer, The Heart Revolution, HarperCollins Publishers, New
York, 1999
10. Berlin, H., Berlin, R., Brante, G., Oral treatment of pernicious
anemia with high doses of vitamin B12 without intrinsic factor, Acta Med
Scand, 184:247-248, 1968
11. Berlin, R., et al, Vitamin B12 body stores during oral and parenteral
treatment of pernicious anemia, Acta Med Scand, 204:81-84, 1978
These statements have not been evaluated by the Food and Drug Administration (FDA). Products are intended to support general well being and are not intended to treat, diagnose, mitigate, prevent, or cure any condition or disease. If conditions persist, please seek advice from your medical doctor.
