A diagnosis of B12 deficiency should not be dismissed based solely on a single measurement of B12 levels in the blood. For classic symptoms of B12 deficiency, a therapeutic trial of B12 supplementation should be considered even if laboratory values are normal.
This is the second video in a five-part series on vitamin B12. If you missed the previous one, check out How Long Does It Take to Become Vitamin B12-Deficient and What Are the Symptoms? (https://nutritionfacts.org/video/how-long-does-It-take-to-become-vitamin-b12-deficient-and-what-are-the-symptoms). Stay tuned for:
• The Best Source of Vitamin B12: Supplements, Shots, or Fortified Foods? (https://nutritionfacts.org/video/the-best-source-of-vitamin-b12-supplements-shots-or-fortified-foods)
• How Much Vitamin B12 Do We Need Each Day? (https://nutritionfacts.org/video/how-much-vitamin-b12-do-we-need-each-day)
• Are Large Weekly Doses of Vitamin B12 Safe? (https://nutritionfacts.org/video/are-large-weekly-doses-of-vitamin-b12-safe)
For more on vitamin B12, check out the topic page (https://nutritionfacts.org/topics/vitamin-b12/).
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“The Best Way to Test for Vitamin B12 Deficiency” Unfortunately, many
diagnoses of B12 deficiency are still made or dismissed based solely
on a single measurement of vitamin B12 levels
in the blood. Why is that unfortunate? Well, first of all, there is
remarkable variability between the results obtained with different
commercially available B12 blood tests. The same sample of blood can come in at 240 pmol/L
in one lab and almost double that
in another. Secondly, there is significant
day-to-day variation of serum B12
within one individual. Here, researchers tested people
once a week for 10 weeks, and the variation
in each individual could be as much
as 100 points or more. One way B12 deficiency
can be missed is when someone takes
a B12 supplement right before getting tested, so, based on their blood levels, it looks like they have
more than enough even if they’re actually
suffering a serious deficiency. On the other hand, perhaps
as many as one in five people who test positive
for B12 deficiency based on low blood B12 levels may not actually be deficient. And then there are those with
symptomatic B12 deficiency who test fine. As many as five percent
of patients who end up being diagnosed
with vitamin B12 deficiency have blood B12 concentrations
above a commonly used cut-off of about 150 pmol/L, and even more have abnormal
MMA or homocysteine levels, which are signs
of functional B12 deficiency even if overt symptoms
are not apparent. Levels of these metabolites
may not normalize until our blood levels
get up to around 400 pmol/L. So, maybe the traditional
cut-off is too low. And it’s not just
lab test abnormalities, those with marginal B12 levels score worse
on hand dexterity tests, suggesting they have covert
diminished nerve function. Most seriously, we can have life-threatening B12 deficiency
with normal blood levels. Here, these two people
were misdiagnosed as having a bone marrow cancer, since it couldn’t be B12,
look how high their levels are. As many as one third of patients with one of the most dreaded
outcomes of B12 deficiency, subacute combined degeneration
of the spinal cord, had normal or even elevated
levels of B12 in their blood. We’re not sure why, but sometimes
the test just fails. Well, that’s not good. Now, if your test result
is really low, like under 100 pg/mL, there’s about
a 90 percent chance you are truly B12 deficient, but if the cut-off amount
is higher like 200 pg/mL, then actual B12 deficiency
could be missed as much as half the time
if you aren’t showing symptoms. The reason
it’s so hard to pin down the rate of false positives
and false negatives is there’s no gold standard
test to compare it to. Some studies suggest
measuring the levels of the biologically active
form of B12, but a wide variation
in levels is also shown depending, in part, on which lab
is running the blood test. Some recommend
using a combination of tests to improve accuracy. For example, one or both
of the functional measures of vitamin B12, MMA, methylmalonic acid,
and homocysteine, perhaps especially
when B12 values are in that so-called
“grey zone” between 150
and 300 pmol/L or so. Those functional measures
are pretty sensitive, meaning if you are B12 deficient there’s more than
a 95 percent chance these tests will pick that up. But there are problems
with so-called specificity, meaning there are other reasons
values can be abnormal, like diminished kidney function
in the case of MMA, and folate deficiency
in the case of homocysteine. In summary, accurate assessment
of vitamin B12 status is problematic,
and there is no consensus as to the best biomarker or combination
of biomarkers to use. From a public health standpoint, what if we just make sure
everyone’s getting their B12? At least 25 countries have mandatory
fortification of staples with vitamin B12,
and that certainly helps. But in terms of testing, if you have classic
B12 deficiency symptoms, even if you have normal
B12 levels in your blood, and even if your MMA and homocysteine levels
are normal, a therapeutic trial
of B12 supplementation should be considered. Meaning, why not just try B12 and see
if your symptoms improve? For example, if you have
neuropathy symptoms, numbness, pins and needles,
loss of a sense of position, or experience
a vibration sensation, maybe you should try going
all out with B12 injections to be absolutely sure. Are B12 injections necessary to
correct B12 deficiency, though? Can it just be treated
with oral B12, and what’s the best source? I’ll answer all those questions next.
