Episode 6 - What is Methylation, and Settling the Score Between Folate and Folic Acid

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There is a lot of confusion around folate versus folic acid.  You might have read that folate is better, but your doctor might have recommended folic acid.  To understand which is truly better, we have to understand a process called methylation.  In this episode, we explore:

• What methylation and DNA methylation is
• How it affects your body
• The essential nutrients for methylation
• Folate vs. folic acid: which is better

I'm curious to hear about your thoughts on this.  Please do not hesitate to contact me.

Follow me on instagram @dradriennewei

Website: www.adriennewei.com

Episode Transcript

Speaker 1 (00:01):
Welcome to the Practically Fertile Podcast.
I'm Adrienne Wee, doctor ofacupuncture and Chinese medicine
, functional medicinepractitioner and functional
nutritionist.
I specialize in using anevidence-based method, blending
principles of East Asianmedicine and modern functional
medicine to help women optimizefertility and get pregnant.

(00:22):
I believe in a world whereevery woman who wants to be a
mother becomes one.
If you're tired of being toldthat you're infertile and you
want to take the right steps toget pregnant naturally and
quickly, this podcast is for you.
I was on a Zoom call with myonline program and we were going

(00:42):
around for Q&A.
One of the members saidsomething like I don't methylate
well, and I saw a lot ofconfused faces.
Everyone was thinking what theheck is methylation Such a funky
word and maybe you've heard ofmethylation and have researched
it.
Maybe this is the first timeyou've ever heard about it, but

(01:05):
I'm sure when you Googlemethylation, you'll come across
methylation DNA methylation,which adds to the confusion.
Does that mean your DNA can bechanged, and what does DNA
methylation have to do withfertility?
We're talking about methylationtoday because it does affect
fertility, fetal development andalso your general health.

(01:26):
It's one of the most importantepigenetic mechanisms and I want
to also use this opportunity tosettle the debate on a very
popular supplement, and that isfolate versus folic acid.
Very often in journal articleson supplements bottles, these
two substances will usually beused interchangeably, when in

(01:48):
fact they're not the same thing.
And don't even get me startedon these shady supplements
companies.
They label their folic acid asfolate.
You'll see folate, and then inparentheses they'll say as folic
acid.
That is just a really unethicalpractice.
I'm also really surprised thatthere's still doctors that

(02:09):
recommend folic acid and thereason is because they say
research shows that it's folicacid that helps with fertility.
But that's not really theentire story.
So let's dive into this.
First, to understandmethylation, we have to
understand what epigenetics is.
Epigenetics determine when ourgenes are turned on and when

(02:32):
they're turned off depending onthe influence from the external
environment.
This does not alter your DNA.
It doesn't change the DNA.
Your DNA makes you human, butyour genes determine your eye
color, your hair color, skintone and everything else that
makes you uniquely.

(02:52):
You and genes also affect verycomplex functions and processes
in the body.
People get cancer when certaingenes are turned on.
We don't want these genes toturn on right.
We want the cancer genes tostay asleep forever.
We also have genes thatinfluence the development of
eggs and sperm.

(03:12):
In fact, studies have foundthat improper DNA methylation in
the sperm was linked tounexplained male infertility.
Genes can affect placenta,making sure that it's a healthy
and can support a healthypregnancy.
Gene mutations can be passed onto the offspring, but they can

(03:34):
also happen later on in life dueto unhealthy lifestyle choices.
The important thing tounderstand, without becoming a
geneticist, is that ourenvironment is a well-known
factor in affecting theepigenetics.
So do you see why now it'simportant that you do work on
your diet, your lifestyle,manage your stress, toxin

(03:55):
exposure, because what you donow will absolutely affect your
baby.
So this process that helps thegenes turn on or off at the
appropriate time is DNAmethylation Methylation process
that specifically involves theDNA.
So methylation and DNAmethylation are slightly

(04:16):
different processes.
Both processes requirenutrients like folate, b12, b6,
choline.
Dna methylation is crucial foregg, sperm and embryo growth,
like we just talked about, andmethylation in general is
crucial for controlling thingslike inflammation, estrogen,

(04:37):
metabolism, detoxification, andall of these are processes that
will impact fertility as well.
Okay, now let's geek out aboutbiochemistry and learn about
methylation, all right.

(04:59):
Very simply put, methylation isa transfer of a methyl group
CH3, between molecules so thatcertain reactions can happen in
the body, and DNA methylation isattaching the methyl group to
the base of one of the proteinsthat make up the DNA Cytosine.
If you must know, methylationreactions are happening a
billion times per second in ourbody without us even knowing

(05:20):
about it, and methylation isresponsible for over 200 types
of reactions in the body.
It's used in DNA synthesis,production of neurotransmitters
like dopamine and serotonin,which help us with our emotional
well-being.
It helps with hormone balance.
It's responsible for theproduction of coenzyme Q10,

(05:43):
which we know that CoQ10 isessential for cellular energy
and therefore it can help withthe egg quality.
Methylation also helps the bodydetox.
It's important in theproduction of glutathione, one
of my favorite supplements.
It's a king of all antioxidantsand glutathione is needed to
reduce oxidative stress andneutralize free radicals that

(06:05):
cause damage to the human body,including the human egg.
So where does folate come intoall of this?
Well, in order for methylationto happen, the methyl group is
provided to the body through auniversal methyl donor, same

(06:25):
S-adenosylmethionine that isproduced from the amino acid
methionine.
The significance of SAMe isthat it readily gives away its
methyl group to the othermolecules in the body, and
that's when methylation happens,when everything is happening
properly.
When methylation happens wheneverything is happening properly

(06:48):
, you'll have plenty of goodmethylation cycles happening in
your body and you'll be in goodhealth.
The problem comes whenmethylation cycles become
sluggish, less effective or justdoesn't happen at all.
Then we have real big problems,not just with reactions in the
body, but also with fertility.
One of these huge issues isthat your detox system becomes

(07:09):
weaker and you end up with lotsof inflammation.
Inflammation is not just abuzzword, it's a very real thing
.
It means that your body is notin its most balanced and healthy
state and inflammation shows upin many, many, many, many
different forms.
Some symptoms of inflammationare hard to measure, but some

(07:30):
are actually measurable, and oneof the substances you can
actually measure is homocysteine.
It's an amino acid that'sactually a toxin.
Homocysteine is easily testedthrough blood work.
If you have elevatedhomocysteine, that means there's
inflammation coming frommethylation issues somewhere.

(07:51):
Here's the thing about folate.
Where does folate come into allthis?
The body cannot actually usedietary folate until it's broken
down into the most active form,which is 5-methyl
tetrahydrofolate, or you mightsee it on the supplement bottle
as 5-methyl-THF.
This is the type of folatethat's usually found in a very

(08:15):
high quality prenatal.
This is important because it'sthis 5-methyltetrahydrofolate
that's needed for your body toconvert the homocysteine, which
is toxic, into methionine andthen to SAMe, and then your body
can use it for methylationcycles.
So you can see, if you don'thave this substance, then none

(08:39):
of this reaction will happen.
Where this can affect pregnancyis, in addition to problems
with gene expression, you couldhave a buildup of homocysteine
in your body, either because youcan't metabolize folate to
break it down to the5-methylhydrotetrafolate, or
maybe the entire process isslower than normal.

(09:00):
Then it will cause inflammationand possibly affect the blood
vessels, blood flow and increasethe risk of blood clots.
So how do you know if you canproperly break down folate?
There's an enzyme called MTHFR5-10-methylene tetrahydrofolate

(09:21):
reductase.
It's a mouthful.
That's why it's called MTHFR.
You may have heard otherstalking about this MTHFR gene
mutation and that it can be acause of recurrent miscarriages.
The gene mutations and genevariants of this enzyme are

(09:41):
super common.
There are over 50 knownvariants of this gene, but only
two of them are problematic.
Of this gene, but only two ofthem are problematic, and those
are the C677T variant and A1298Cvariant.
And even if you were found tohave this gene variant, it

(10:02):
matters if it's a heterozygousor a homozygous variant.
We all have two MTHFR genes,one inherited from each parent.
Heterozygous variant means thatyou only have one copy of the
gene that's mutated, andhomozygous variant means that

(10:23):
you have two copies of the genesthat are mutated.
The frequency of a heterozygousC677T mutation is common,
occurring in about 35% of thepopulation.
The homozygous C677T mutationis about 5 to 10% of the
population.
A mutation in A129AC is morecommon but is generally less

(10:50):
problematic.
The homozygous variety ofA129AC occurs in 9% of the
population.
If you have the MTHFR mutation,it does not automatically mean
that you're going to miscarry.
In fact, many of my patientsdon't even know that they have
the gene mutation becausethey've had one successful

(11:11):
pregnancy and didn't think thatit could be a problem conceiving
for the second time.
But even having theheterozygous variant can affect
folate metabolism and thereforethe homocysteine metabolism and
the methylation cycle.
So it's very possible thatmethylation isn't as effective
as before and that's why it'scausing issues with fertility in

(11:34):
pregnancy the second timearound.
So if you do have problems withthe MTHFR gene, two common
treatments are using folateinstead of folic acid,
specifically the5-methyltetrahydrofolate,
because this bypasses the needto use the enzyme to break down
the folate.

(11:55):
It's already the end productthat our body can use, and also
aspirin, heparin or lovinox whenyou get pregnant to prevent
blood clotting.
Now let's get to the bigquestion why not folic acid?
The thing about folic acid isthat it's synthetic.

(12:15):
It's not natural to your body.
It's made in the lab and itrequires multiple steps to break
down into the active form offolate 5-methyltetrahydrofolate.
It will require a completelydifferent enzyme called
dihydrofolate reductase toreduce it to tetrahydrofolate

(12:38):
and then that gets broken downinto the methyl tetrahydrofolate
.
The problem is how well thisdihydrofolate reductase can
break down folic acid.
It varies a lot between personto person.
It's different for everyone.
A lot between person to person.

(12:59):
It's different for everyone.
Some people have no problem,some people will have issues and
unmetabolized folic acid.
So if you're one of thosepeople that can't break down the
folic acid, it can actuallystay in your body and this has
become a matter of concern.
It's now been given an officialname unmetabolized folic acid
syndrome.
It can be found in theumbilical cord and infant blood,

(13:22):
and we actually don't know theextent of the syndrome and its
impact on the baby and thehealth moving forward.
So why put your body through allthis work when you can just
take the5-methyltetrahydrofolate without
the need to use themethyltetrahydrofolate reductase

(13:43):
?
And I want to say one thing too.
So if your doctor recommendsfolic acid and says that folic
acid has been shown to beeffective in reducing the risk
of neural tube defects andthat's because most, if not all,
the studies have been doneusing folic acid, since it's

(14:04):
heat stable and it's very cheapto make, and using folate is way
more expensive so your doctoris not wrong.
But if she says that folic acidis better than folate, then
that's wrong for all the reasonsthat we just mentioned before.
Now the big question is shouldyou test for the MTHFR genetic

(14:27):
variant?
It's not part of the routinefertility workup.
In fact, even if you hadmultiple miscarriages, not all
the doctors would test you forthis variant.
I had a patient who wentthrough five miscarriages and
her doctor never tested her forthe MTHFR.
Oh, that's such a mouthful,because her homocysteine levels

(14:47):
were always normal.
But it turned out she did havethis genetic mutation and as
soon as she was treated properly, she went on to have two
healthy pregnancies.
I have tested patients beforeusing a very inexpensive saliva
test and discovered that she hadthe homozygous MTHFR mutation.

(15:10):
So I'm glad that we discoveredthis and we made sure that she
was taking enough folate andalso that her doctor was aware
of this, so when she getspregnant it can be managed
properly, given that methylationis so critical during the
embryo development in the firsttrimester and this is another
reason why I just recommendfolate anyway because the remedy

(15:30):
for having this gene mutationis just to take the folate the
5-methyltetrahydrofolate.
I typically recommend 600 to800 micrograms of folate the
5-methyltetrahydrofolate.
I typically recommend 600 to800 micrograms of folate for
pre-pregnancy and duringpregnancy.
It's a very safe supplementsince it's water-soluble, so
you're not at risk ofaccumulating it.
All right, fertile friend,we're at the end of the episode

(15:53):
here.
I want to circle back to thebeginning, when my patient made
a comment about how she didn'tmethylate.
Well, there are tests that candetermine whether or not this is
indeed the case.
I run a few tests that candetermine where the nutritional
deficiencies are and how exactlymethylation is affected.
These tests are very expensiveand even though they do give you

(16:16):
some really cool informationand suggestions on which
nutrients to supplement.
The simplest remedy short termis just to make sure that you're
using a high quality folate,but the long term remedy most
likely is to make sure thatwe're influencing DNA
methylation and methylationpositively by managing
environmental factors like diet,lifestyle, stress, toxin

(16:39):
exposure.
I'm curious to hear about yourthoughts on this.
If this is the first timeyou're hearing about methylation
or if you have any questionsabout it, please let me know.
You can find me on Instagram asDr Adrienne Wee or you can send
me a text through the podcastdirectly.
I would love to hear from you.
Thank you so much for spendingsome time with me today.

(17:00):
Fertile friend, until next time, take care of yourself and your
amazing body.
You are one fertile cycle awayfrom getting pregnant.