UNDIAGNOSED
VITAMIN B12 DEFICIENCY?
A vitamin B12 deficiency is most often caused by digestive system difficulties, which can occur if the body is unable to absorb B12 from foods and liquids.
Most frequently this is due to a lack of intrinsic factor from the stomach or insufficient acid in the stomach.
Digestive diseases that can affect absorption include inflammatory bowel disease, celiac disease, autoimmune disorders such as pernicious anemia, or diseases of the pancreas.
Additionally,
some medications impair B12 absorption.
Other causes include undergoing certain types of bariatric surgery
that remove part of the stomach; bacterial overgrowth, which competes for
vitamin B12; and alcohol consumption.
Elders are at a higher risk of developing a deficiency mainly due to decreasing absorption along with dietary changes or decreased food intake.
Individuals who mainly eat a vegetarian diet are also susceptible since B12 is
found strictly in animal products.
Preventing Deficiencies
Deficiency problems typically arise as patients age.
The Institute of Medicine recommends that individuals aged 50 and older receive vitamin B12 from synthetic sources (a supplement or fortified product) because unlike those naturally occurring in foods, the B12 is unbound and more apt to be available to the bowel for absorption.
Explains Christy C. Tangney, PhD, CNS, FACN, an
associate professor in the department of clinical nutrition at Rush University
Medical Center in Chicago, who also headed a study on B12 and adults over the
age of 65 that was published in the September 27, 2011, issue of Neurology.
Patients should strive to maintain diets that contain a sufficient level of B12.
Some foods that have a good amount of B12 content are meat, dairy
products, eggs, poultry, and foods fortified with B12, such as cereals and soy
milk.
If a patient has a preexisting condition that may limit B12 absorption, then a combination of B12 supplements with or without monthly B12 injections can effectively manage the deficiency.
“The elderly are especially at risk of developing a B12 deficiency since absorption issues and poor dietary intake are more probable,” says Mark Gottlieb, DO, a family practice physician at Paoli Hospital in Pennsylvania.
In fact, approximately 3% of individuals aged 51 and
older will develop a B12 deficiency, according to the Centers for Disease
Control and Prevention.
Detecting B12 Deficiency
Standard blood tests can detect B12 deficiency; however, the cutoff levels for deficiency (less than 200 pmol/L) may be inadequate, as some recent studies suggest a better cutoff may be possibly 300 to 350 pmol/L or higher.
Some individuals
with a low-normal B12 level in the blood can exhibit symptoms of B12
deficiency.
Previously, if a patient was at risk of poor B12 absorption, a Schilling test was performed.
The test uses radioisotopes to measure B12 absorption. B12-dependent metabolism causes the formation of methionine from homocysteine and the formation of succinyl coenzyme A from methylmalonyl coenzyme A.
Therefore, an elevated level of homocysteine and methylmalonic acid (MMA) can
indicate a B12 deficiency. Urinary excretion of MMA can also indicate B12
deficiency if markedly elevated.
The Schilling test, which, according to Tangney, is laborious for the
patient but a “truly great diagnostic test,” is rarely performed because of the
small amounts of radioactive compound that must be measured by laboratories
that often no longer have these counters.
Making a Definitive Diagnosis
The best way to make a definitive diagnosis of B12 deficiency is with a
thorough history and physical exam followed by a blood test that evaluates B12
and folate levels since symptoms of folate deficiency can be similar to those
of B12 deficiency, according to Gottleib.
Numerous patients have both a B12 and a folate deficiency.
If B12 levels are in the low-normal range, MMA and homocysteine levels can be measured.
If
B12 deficiency is shown, a thorough review of dietary habits as well as a
Schilling test can indicate either poor B12 intake or poor absorption if no
other factors are present.
Certain scenarios can give a mismatch between tissue and blood levels,
causing a false-positive for B12 deficiency.
B12 Deficiency and Cognitive Decline
The association of B12 deficiency and neurological symptoms is well documented, as noted in the Chicago Health and Aging Project, a longitudinal population study of common chronic health problems of older adults, especially of risk factors for incident Alzheimer’s disease.
B12 is necessary for maintenance of the myelin sheath of nerves.
Recent research reports on several relationships between a correlation with levels of B12-related markers (but not serum B12) and standardized neuropsychological tests of cognition itself as well as global cognitive function and total brain volume.
Methylmalonate levels were associated with poorer episodic memory and perceptual speed, and cystathionine and 2-methylcitrate with poorer episodic and semantic memory.
Homocysteine
levels were associated with decreased total brain volume.
Therefore, markers of B12 deficiency but not serum B12 levels themselves may correlate with cognition and brain volume.
According to the Rush study,
results showed that high levels of four of five markers for B12 deficiency were
associated with lower scores on cognitive tests and smaller brain volume.
Long-Term Effects
There is a strong clinical understanding that vitamin B12 deficiency syndrome is irreversible if left untreated.[1]
Some of the aforementioned declines may be reversible if the deficiency is recognized early.
“The longer the deficiency persists, the higher the likelihood that irreversible and permanent damage will occur,”
says Brian Dixon, PhD, director of product innovation at USANA Health Sciences in Salt Lake City.
Most likely, long-term damage is not reversible
with B12 repletion.
Vitamin B12 deficiency results in megaloblastic anemia and neurologic symptomatology, including disease of the spinal cord (subacute combined degeneration of the spinal cord), nerves (peripheral neuropathy), and brain (disturbance of mood and cognition).
The exact serum level cutoffs necessary to
diagnose deficiency are unclear, and deficiency states with clinical
symptomatology have been identified at normal serum levels.[2-4]
The thought is that if clinicians rely on blood smears, hematocrit, or hemoglobin levels to assess anemia, the neurological sequelae may be missed and allowed to progress,
Tangney says. These are subtle changes that may progress and become irreversible if no treatment is offered for correction.
High-dose
vitamin B12 therapy can resolve symptoms of the neurologic syndrome, including
cognitive disturbances.[5,6]
— Karen Appold is a freelance medical writer in Royersford,
Pennsylvania.
References
1. Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of cognitive
recovery with cobalamin replacement: report of a pilot study. J Am
Geriatr Soc. 1992;40(2):168-172.
2. Solomon LR. Cobalamin-responsive disorders in the ambulatory care
setting: unreliability of cobalamin, methylmalonic acid, and homocysteine
testing. Blood. 2005;105(3):978-985.
3. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric
disorders caused by cobalamin deficiency in the absence of anemia or
macrocytosis. N Engl J Med. 1988;318(26):1720-1728.
4. Saperstein DS, Wolfe GI, Gronseth GS, et al. Challenges in the
identification of cobalamin-deficiency polyneuropathy. Arch Neurol.
2003;60(9):1296-1301.
5. Allen RH, Stabler SP, Lindenbaum J. Relevance of vitamins, homocysteine and
other metabolites in neuropsychiatric disorders. Eur J Pediatr.
1998;157 Suppl 2:S122-126.
6. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J.
Effective treatment of cobalamin deficiency with oral cobalamin. Blood.
1998;92(4):1191-1198.
https://www.todaysgeriatricmedicine.com/archive/012312p30.shtml
Which Vitamin B12 Tests are Available?
No tests are yet able to give clear information about B12 levels. Presently, a number of tests are in use, all of which have certain advantages and disadvantages. The standard test in general medicine is the serum test, which is the oldest but by far most unreliable B12 test of all.
| Test | What does it measure? | Reliability |
| Serum | Total B12 level in the blood | Poor. Severe deficiencies can be detected, but higher values have no relevance or significance. The test also includes unavailable B12 and B12-like substances |
| Holo TC | Bioavailable B12 which binds with transcobalamin in the blood | High. However with a grey area, in which the diagnosis is uncertain. |
| Homocysteine | Homocysteine levels in the blood | Medium. Numerous other factors could also play a role. |
| MMA | Methylmalonic acid levels in the urine | High. Only a handful of other factors. |
Test Sensitivity
Vitamin B12 deficiency proceeds in several phases; the various tests unfortunately cannot provide reliable results in all of them:
- Phase 1: undersupply, the body begins to empty its B12 stores, cells remain supplied
- Phase 2: stores are critical, B12 deficiency in the cells
- Phase 3: severe, clinical deficiency
