good evening i’m dr david ferriss one of
the physicians at maxwell clinic
and it’s my pleasure to host
this month’s
group visit
tonight we’ll be talking about
homocysteine
what it is and why it’s important
so
i want to address uh three different
aspects of homocysteine this evening
first what is homocysteine
uh second what effect does elevated
homocysteine have on health
and with particular attention to
cardiovascular health and brain health
and then if elevated how does one lower
his or her homocysteine
so let’s look first at
what is homocysteine
well homocysteine is an amino acid that
is normally found in the body
you may recall from your high school or
your
college biology that amino acids are the
building blocks of all proteins
every protein of every type
is constructed by through a combination
a linkage of various amino acid building
blocks so homocysteine
is
one amino acid
and
normally in the body homocysteine is
converted to two other amino acids that
are essential for good health
to cysteine
and methionine
but when this conversion is impaired
homocysteine levels build up in the body
and that can cause issues which we’re
going to talk about
in in some detail
a couple of other facts about
homocysteine and and why elevated levels
are important
um i mentioned that homocysteine is
normally converted to these two other
amino acids cysteine and methionine
methionine is particularly important
because it uh it plays a key role in the
generation
of molecules that we call methyl groups
if you’ve had organic hist organic
chemistry you know that methyl groups
are comprised of one carbonite atom and
three hydrogen atoms
and these methyl groups are required for
the
synthesis of dna for the repair of dna
and the dna in our bodies is under
constant assault
from
um
from free radicals that are generated
through normal
metabolism in the in the cells through
from radiation
from various chemical toxins in the
environment so it’s very important that
we have adequate levels of methionine
in the body
to
support
this
this methylation this dna
repair
so there are a number of causes of
elevated homocysteine
one of those can be a deficiency of
folate and other
b
vitamins in the diet
we’ll talk a bit more about this in a
few minutes
but the
key enzyme
that converts homocysteine
into cysteine and methionine is very
dependent
on having
access to adequate b vitamins in order
to function properly so if there’s a
deficiency of folate
and other b12 vitamins in one’s diet
this can contribute to elevated
homocysteine levels
we also see elevated homocysteine levels
in some patients with kidney disease
that have renal failure
it can be seen in patients with low
thyroid hormone levels
and some patients with psoriasis
a skin condition
and there are certain medications such
as anti-seizure
medications and methotrexate
a
a chemical that is used in cancer
treatment and also
often to treat
autoimmune diseases such as rheumatoid
arthritis
these medications can also contribute to
an elevation in homocysteine
a major cause of elevated homocysteine
though in a significant number of
individuals
is is a genetic uh variant
in a key gene that governs
this enzyme
called methylene tetrahydrofolate
reductase i know it’s quite a mouthful
or abbreviated mthfr
this is the key enzyme that i mentioned
that converts homocysteine into cysteine
and methionine
so
some individuals in the population it’s
not uncommon at all
have a genetic variation
that uh decreases the efficiency of this
uh this enzyme that converts
homocysteine into cysteine and
methionine and we’ll come back to talk
about that again in a few minutes when
we talk about how do we treat how do we
lower
elevated levels of homocysteine
we also know that homocysteine
increases with age so as we get older
homocysteine levels can tend to increase
and homocysteine levels may also be
affected by things such as cigarette
smoking alcohol
consumption
and a
sedentary lifestyle
all right so with that is background
about homocysteine what it is and why
it’s important
i want to i want to go further about why
it’s important and what kind of impact
it has on various organ systems
so here you’ll see a diagram i’m sorry
it’s not in color but it’s not this
comes from um
a major review article on homocysteine
uh by tinnelli and uh his colleagues in
frontiers of nutrition from the april
2019 issue but i think it illustrates
well
why we’re concerned about homocysteine
and why we want to try to optimize
uh its level
when when it’s elevated in the body
so you see
the the the big
uh tag at the at the top of um
above the
molecular
structure of homocysteine there in the
middle
titled the cardiovascular system
and this is a a major system of the body
that there are number of correlations
between elevated homocysteine and
cardiovascular disease
we know from a number of studies that
elevated homocysteine levels
promote
atherosclerotic lesion progression
and are associated with atherogenesis so
that’s a fancy way of saying
that elevated homocysteine can
contribute to the development of
atherosclerotic plaque in the coronary
arteries and in other arteries of the
body
elevated homocysteine
also inhibits the production of a
substance called nitric oxide
nitric oxide is an important chemical
that is produced by a healthy
microvascular system by a healthy
endothelial lining
of the vasculature particularly the the
arteries and nitric oxide is a potent
vasodilator
and so it’s very important that
our arteries and other vessels are able
to dilate as needed to meet the body’s
needs and they can only do this if there
are
adequate production of nitric oxide and
that’s very dependent on a healthy
microvascular system
and as i said elevated homocysteine
inhibits the production of nitric oxide
there’s also a correlation between
elevated homocysteine and elevated blood
pressure
elevated homocysteine is a confirmed
coronary artery disease risk factor
so your risk goes up for coronary
artery disease with elevated
homocysteine
and elevated homocysteine has also been
found to be an independent risk factor
for stroke
so again more reasons why
we want to
make sure that homocysteine levels
aren’t extremely high and optimized
whenever possible
let’s move on to
the brain
so this is the other very important
organ that’s impacted by elevated
homocysteine
we know that elevated homocysteine from
what we just said damages the walls of
arteries and that includes the arteries
and the microvascular blood supply of
the brain so if that’s impacted that’s
damaged then it makes sense that
our brains are not going to function as
we want them to function
a researcher named sashdev and his
colleagues found in a study
that elevated homocysteine increases the
risk of vascular disease especially
small vessel disease which can lead to
brain atrophy that is an actual
shrinkage of of the brain
another researcher fung
and his colleagues found that elevated
homocysteine is associated with impaired
cognitive performance and increases the
risk that one has for cognitive decline
and dementia
fung and his colleagues also found that
there’s an associated as i’m sorry an
association between elevated
homocysteine and decrea decreased white
matter in the brain
uh there are two types of matter on a
gross anatomy basis uh in the brain
there’s gray matter
and white matter gray matter actually
the the the neurons the neuron cell
bodies
uh dendrites and
the axons the connecting lengths of one
neuron to another
comprises the white matter
and so
if there is elevated homocysteine that
has been associated with
actually
decreased white matter in the brain
which impacts brain function
a researcher named nelson and his
colleagues
found that and concluded that
homocysteine
actually uh can be neurotoxic
and can consequently adversely affect
memory performance it can damage the
neurons of the brain which are the
the the essential
uh types of cells um that are found in
the brain and and brain function depends
on
elevated homocysteine uh has been shown
to play a role
in the development of various diseases
affecting the nervous system so this
includes stroke
parkinson’s disease alzheimer’s disease
multiple sclerosis and epilepsy
and elevated homocysteine results in the
production of reactive oxygen species
sometimes better known as free radicals
which also can directly damage the
neurons in the brain
all right let’s move around clockwise
to some of the other organ systems that
elevated homocysteine
impacts the next is sensory organs
elevated homocysteine has been
associated
in cases of sudden hearing loss
and elevated homocysteine
is been found to be a risk factor for
age-related macular degeneration
the macula is that very specialized part
of the retina that is most sensitive and
that
we depend on
to
when we focus on something
when we
um to do any kind of close work detailed
work to read
um
it’s it’s absolutely essential that we
have a healthy macula and in some
individuals there’s a genetic component
to this
but uh particularly as they age as they
get into their 60s 70s 80s and beyond
there can be gender degeneration of the
macula
which leaves the these individuals uh
severely constrained in their ability to
to see
at best they increasingly have just some
peripheral vision they may be able to
navigate
around
but
or see things kind of out of their
peripheral vision but anything that they
would ordinarily focus on
to read to watch television to work from
a computer increasingly becomes
compromised so it’s an important
disabling condition
and elevated homocysteine has been found
to be a risk factor for helping promote
that
if we move next to the reproductive
system
elevated homocysteine during pregnancy
has been associated with placental
vascular damage and that can result in
spontaneous abortion and a condition
called preeclampsia
which is a very dangerous condition that
can affect uh pregnant women
uh typically in the
the latter trimester of
of of their pregnancy
and when it occurs can require immediate
medical intervention
elevated homocysteine can also
help contribute to
gestational diabetes
women who while they are pregnant they
don’t have diabetes they don’t have
elevated blood sugar when they’re
non-pregnant but when they’re pregnant
they they develop elevated blood sugars
which does place them at high risk
next moving around uh is the endocrine
system
there appears to be a correlation of
elevated homocysteine with
diabetes complications
and we know that patients with
microalbuminuria
small amounts of albumin in their urine
and proliferating retinopathy which is a
com is a complication
of diabetes
patients with this have been
demonstrated to have homocysteine levels
significantly higher than those of
patients without those complications so
we don’t know specifically whether the
homocysteine actually causes
these things
but
it certainly is is correlated it’s
associated with it
next moving around um
this this circle uh the skeletal system
elevated homocysteine is associated with
an increased risk of osteoporotic bone
fracture
so osteoporosis is a loss of
mineralization
in the in the bones particularly it
impacts
the hips and the femur
and affects the vertebral
bodies of the spine
and this can lead
with progressive osteoporosis
to uh fractures in the verdebral bodies
particularly the
lumbar vertebral bodies and in the
um the hip
which
moving around finally to
the adrenal system the kidney
as renal function decreases we know that
homocysteine levels
increase
and in fact in one case control study
85
of hemodialysis patients had
homocysteine levels above the 95th
percentile of the control group so
there’s a very strong
association there
so i i think you can see from our
walking around this diagram
certainly the cardiovascular system
heart health brain health
are very important but a number of other
organ systems are involved as well
when it comes to elevations in
homocysteine
so
um all that’s fine and good
but if elevated how does one lower it
and so i should say here
that um
virtually all new patients at maxwell
clinic as part of their initial new
patient
laboratory workup
have their homocysteine measured
and
you may have noticed if you’ve seen your
own lab reports with the homocysteine
test results
that
i think labcorp has a normal range or
what we call a reference range of 0 to
about 15.
um
we don’t think that that’s optimal if
it’s certainly in above 10 to 15
we think optimal levels are probably in
the
seven to eight range or lower
and certainly we’d like to see all of
our patients lower than than 10 if
possible
is homocysteine levels increase into the
20s 30s and there’s some very few
patients that’s relatively rare can even
have homocysteine levels uh of a hundred
or or more and certainly the higher the
homocysteine level the the greater the
risk
but let’s talk uh finally
about what do we do how do we address
um
elevated levels of homocysteine when
when that’s a finding
so we we’ve already talked about
how the conversion of homocysteine
to cysteine and methionine is dependent
on a key enzyme methylene
tetrahydrofolate
reductase are abbreviated mthfr
and this enzyme requires
b vitamins b12 b6 and particularly
folate
in order to function normally
so
um
in
individuals that are deficient in b
vitamins especially folate in their diet
this can result in elevated
homocysteine levels
so what are some of the foods
that it’s important sources of folate
well fruits and vegetables especially
green leafy vegetables
uh folate fortified breads and cereals
because of the risk of low folates and
in particularly in pregnant women the
development of um
neural
tunnel defects
in the in the
in the developing baby
then a number of cereals and breads have
have been fortified uh with folate to
put additional folate into the diet what
i meant to say was neural tube
defects
so things such as spina bifida
uh would be an example of that
um
other foods that are rich in folate are
lentils chickpeas asparagus spinach
and in most legumes most beans
but dietary sources may not be
sufficient
in in many patients and so that’s where
often what we will do is certainly
encourage
our patients with elevated homocysteine
levels
to um to to eat a healthy diet and one
in which they’re going to eat the foods
i just mentioned
uh but many times that’s that’s not
enough or it’s not consistent
and so we will supplement with a mixture
of b vitamins uh that is a b vitamin
complex
one of the the primary supplements we
use at maxwell clinic
is creating health gene protect which is
a mixture of b2
b6 b12 and folate so it’s it’s a b
vitamin complex
and when we
uh start an individual on this typically
it may be one capsule a day or often one
capsule twice a day we’ll start
and then we’ll recheck the homocysteine
level a couple of months later
and usually we see a very good response
and the homocysteine level will come
down
to certainly less than 10 and often to
you know that optimal range of seven or
eight somewhere in that range or even
even lower
uh and when that happens uh you know we
we’ve achieved that that optimal range
that that we’re seeking
in some individuals with uh much higher
levels of homocysteine say homocysteine
in the 20s or 30s or higher
we will use a product called folify er
for extended release
this is a much higher dose of folate
and
so in in some cases where we we need to
get much higher doses of folate
we’ll use uh volify er but the vast
majority of our our patients respond
very well to uh creeding health gene
protect
and the reason as we’ve already alluded
to that it’s called gene protect is
because of the importance of
homocysteine
in this uh methionine
biochemical pathway
and and making sure that we have
sufficient levels of methionine
in order to
to produce that dna repair that each of
us continuously needs
so
that’s uh probably more than you wanted
to know about homocysteine
why we think it’s important to measure
it
and and why we pay attention to it uh
but i hope this has been helpful to
provide some some more detail
and
i’m going to
stop my
screen share for the presentation
and see if uh if there are any questions
that i can try to uh to answer
so um i don’t see any uh any questions
uh i hope this has made sense to you and
has been been helpful
so if there are no open
questions
then thank you for attending i
appreciate your attendance and
have a have a really good evening take
care
