Symptoms
of vitamin B12 deficiency and
hypothyroidism
Many of
the symptoms of hypothyroidism are
similar to the symptoms of vitamin B12
deficiency. Thus,
fatigue, weakness,
depression, irritability, memory loss,
abnormal menstrual cycles, decreased
libido and poor mental growth are
similar. to both conditions. Confounding the situation is
that there
is a high (approx 40%) prevalence of
vitamin B12
deficiency
in hypothyroid patients. Traditional
symptoms are not a good guide to
determining presence of
B12
deficiency.
Screening for
vitamin
B12 levels should be undertaken
in all hypothyroid patients,
irrespective of their thyroid antibody
status.
Why hypothyroidism leads
to vitamin B12
deficiency.
Normal cycling of folate
results in the formation
of an irreversible
reaction in which 5, 10
methylenetetrahydrofolate
is converted to
5-methyltetrahydrydrofolate
(5-MTHF) by the enzyme
5,10
methyltetrahydrofolate
reductase (MTHFR). Of
note in this reaction is
that MTHFR uses FAD
(derived from
riboflavin, vitamin
B2) as an essential
cofactor. In addition,
the reduction that
occurs requires input
from NADH + H+
(derived from
nicotinamide,
vitamin B3). In the
absence of these two
vitamins (B2/B3) the
enzyme is not
functional. In this
situation, folate is not
able to recycle via the
conversion of
5,10-methenyltetrahydrofolate
to
5-methyltetrahydrofolate.
This leads to an
intracellular deficiency
of folate, MeCbl,
methionine and SAM.
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Role of the Thyroid in
FAD synthesis
Synthesis of Flavin
Mononucleotide (FMN) from
riboflavin requires the
addition of phosphate
from ATP, via riboflavin
kinase, with the input
of triiodothryonine (T3)
and thyroxine (T4). Both
T3 and T4 are produced
in the thyroid following
stimulation by thyroid
stimulating hormone
(TSH). The
subsequent synthesis of
FAD from FMN also
involves contribution of
thyroxin in the presence
of FAD plus AMP.
Deficiency in thyroxine,
due to hypothyroidism
can result in reduced
levels of FAD in the
body. Similarly dietary
deficiency in either
iodine and/or riboflavin
can result in reduced
FAD.
In persons with
hypothyroidism, or
vitamin B2, or vitamin
B3 deficiency, or those
who have mutations in the MTHFR
gene, the MTHFR enzyme has
reduced activity and so
the amount of 5MTHF
that is synthesized is
reduced,
and so the 5MTHF + OHCbl
<=> THF + MeCbl reaction
cannot operate
efficiently and hence
supplies of MeCbl are
rapidly turned into
inactive OHCbl. (The
extent of reduction is
dependent upon the
extent of deficiency or how many
and which types of
mutations occur in the
MTHFR gene). As a
consequence, the
normal addition of the
methyl group from the
folate cycle is reduced
and so must be supplied by
MeCbl.
As the methyl group
cannot be recycled via
the normal route, every
methyl group used in
synthesis must be
supplied by
MeCbl.
This leads to
rapid depletion of VB12
stores.
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