Practically Fertile

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

• Dr. Adrienne Wei, DACM, FABORM, CFN, L.Ac.

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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

Speaker 1:

Welcome to the Practically Fertile Podcast. I'm Adrienne Wee, doctor of acupuncture and Chinese medicine, functional medicine practitioner and functional nutritionist. I specialize in using an evidence-based method, blending principles of East Asian medicine and modern functional medicine to help women optimize fertility and get pregnant. I believe in a world where every woman who wants to be a mother becomes one. If you're tired of being told that you're infertile and you want to take the right steps to get pregnant naturally and quickly, this podcast is for you.

Speaker 1:

I was on a Zoom call with my online program and we were going around for Q&A. One of the members said something like I don't methylate well, and I saw a lot of confused faces. Everyone was thinking what the heck is methylation Such a funky word and maybe you've heard of methylation and have researched it. Maybe this is the first time you've ever heard about it, but I'm sure when you Google methylation, you'll come across methylation DNA methylation, which adds to the confusion. Does that mean your DNA can be changed, and what does DNA methylation have to do with fertility? We're talking about methylation today because it does affect fertility, fetal development and also your general health. It's one of the most important epigenetic mechanisms and I want to also use this opportunity to settle the debate on a very popular supplement, and that is folate versus folic acid. Very often in journal articles on supplements bottles, these two substances will usually be used interchangeably, when in fact they're not the same thing. And don't even get me started on these shady supplements companies. They label their folic acid as folate. You'll see folate, and then in parentheses they'll say as folic acid. That is just a really unethical practice. I'm also really surprised that there's still doctors that recommend folic acid and the reason is because they say research shows that it's folic acid that helps with fertility. But that's not really the entire story. So let's dive into this. First, to understand methylation, we have to understand what epigenetics is.

Speaker 1:

Epigenetics determine when our genes are turned on and when they're turned off depending on the influence from the external environment. This does not alter your DNA. It doesn't change the DNA. Your DNA makes you human, but your genes determine your eye color, your hair color, skin tone and everything else that makes you uniquely. You and genes also affect very complex functions and processes in the body. People get cancer when certain genes are turned on. We don't want these genes to turn on right. We want the cancer genes to stay asleep forever. We also have genes that influence the development of eggs and sperm. In fact, studies have found that improper DNA methylation in the sperm was linked to unexplained male infertility. Genes can affect placenta, making sure that it's a healthy and can support a healthy pregnancy. Gene mutations can be passed on to the offspring, but they can also happen later on in life due to unhealthy lifestyle choices.

Speaker 1:

The important thing to understand, without becoming a geneticist, is that our environment is a well-known factor in affecting the epigenetics. So do you see why now it's important that you do work on your diet, your lifestyle, manage your stress, toxin exposure, because what you do now will absolutely affect your baby. So this process that helps the genes turn on or off at the appropriate time is DNA methylation Methylation process that specifically involves the DNA. So methylation and DNA methylation are slightly different processes. Both processes require nutrients like folate, b12, b6, choline. Dna methylation is crucial for egg, sperm and embryo growth, like we just talked about, and methylation in general is crucial for controlling things like inflammation, estrogen, metabolism, detoxification, and all of these are processes that will impact fertility as well.

Speaker 1:

Okay, now let's geek out about biochemistry and learn about methylation, all right. Very simply put, methylation is a transfer of a methyl group CH3, between molecules so that certain reactions can happen in the body, and DNA methylation is attaching the methyl group to the base of one of the proteins that make up the DNA Cytosine. If you must know, methylation reactions are happening a billion times per second in our body without us even knowing about it, and methylation is responsible 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 the production of coenzyme Q10, which we know that CoQ10 is essential for cellular energy and therefore it can help with the egg quality.

Speaker 1:

Methylation also helps the body detox. It's important in the production of glutathione, one of my favorite supplements. It's a king of all antioxidants and glutathione is needed to reduce oxidative stress and neutralize free radicals that cause damage to the human body, including the human egg. So where does folate come into all of this? Well, in order for methylation to happen, the methyl group is provided to the body through a universal methyl donor, same S-adenosylmethionine that is produced from the amino acid methionine. The significance of SAMe is that it readily gives away its methyl group to the other molecules in the body, and that's when methylation happens, when everything is happening properly. When methylation happens when everything is happening properly, you'll have plenty of good methylation cycles happening in your body and you'll be in good health.

Speaker 1:

The problem comes when methylation cycles become sluggish, less effective or just doesn'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 is that your detox system becomes weaker and you end up with lots of inflammation. Inflammation is not just a buzzword, it's a very real thing. It means that your body is not in its most balanced and healthy state and inflammation shows up in many, many, many, many different forms. Some symptoms of inflammation are hard to measure, but some are actually measurable, and one of the substances you can actually measure is homocysteine. It's an amino acid that's actually a toxin. Homocysteine is easily tested through blood work. If you have elevated homocysteine, that means there's inflammation coming from methylation issues somewhere.

Speaker 1:

Here's the thing about folate. Where does folate come into all this? The body cannot actually use dietary folate until it's broken down into the most active form, which is 5-methyl tetrahydrofolate, or you might see it on the supplement bottle as 5-methyl-THF. This is the type of folate that's usually found in a very high quality prenatal. This is important because it's this 5-methyltetrahydrofolate that's needed for your body to convert the homocysteine, which is toxic, into methionine and then to SAMe, and then your body can use it for methylation cycles. So you can see, if you don't have this substance, then none of this reaction will happen. Where this can affect pregnancy is, in addition to problems with gene expression, you could have a buildup of homocysteine in your body, either because you can't metabolize folate to break it down to the 5-methylhydrotetrafolate, or maybe the entire process is slower than normal. Then it will cause inflammation and possibly affect the blood vessels, blood flow and increase the risk of blood clots. So how do you know if you can properly break down folate? There's an enzyme called MTHFR 5-10-methylene tetrahydrofolate reductase. It's a mouthful. That's why it's called MTHFR.

Speaker 1:

You may have heard others talking about this MTHFR gene mutation and that it can be a cause of recurrent miscarriages. The gene mutations and gene variants of this enzyme are super common. There are over 50 known variants of this gene, but only two of them are problematic. Of this gene, but only two of them are problematic, and those are the C677T variant and A1298C variant. And even if you were found to have this gene variant, it matters if it's a heterozygous or a homozygous variant. We all have two MTHFR genes, one inherited from each parent. Heterozygous variant means that you only have one copy of the gene that's mutated, and homozygous variant means that you have two copies of the genes that are mutated. The frequency of a heterozygous C677T mutation is common, occurring in about 35% of the population. The homozygous C677T mutation is about 5 to 10% of the population. A mutation in A129AC is more common but is generally less problematic. The homozygous variety of A129AC occurs in 9% of the population.

Speaker 1:

If you have the MTHFR mutation, it does not automatically mean that you're going to miscarry. In fact, many of my patients don't even know that they have the gene mutation because they've had one successful pregnancy and didn't think that it could be a problem conceiving for the second time. But even having the heterozygous variant can affect folate metabolism and therefore the homocysteine metabolism and the methylation cycle. So it's very possible that methylation isn't as effective as before and that's why it's causing issues with fertility in pregnancy the second time around. So if you do have problems with the MTHFR gene, two common treatments are using folate instead of folic acid, specifically the 5-methyltetrahydrofolate, because this bypasses the need to use the enzyme to break down the folate. It's already the end product that our body can use, and also aspirin, heparin or lovinox when you get pregnant to prevent blood clotting.

Speaker 1:

Now let's get to the big question why not folic acid? The thing about folic acid is that it's synthetic. It's not natural to your body. It's made in the lab and it requires multiple steps to break down into the active form of folate 5-methyltetrahydrofolate. It will require a completely different enzyme called dihydrofolate reductase to reduce it to tetrahydrofolate and then that gets broken down into the methyl tetrahydrofolate. The problem is how well this dihydrofolate reductase can break down folic acid.

Speaker 1:

It varies a lot between person to person. It's different for everyone. A lot between person to person. 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 those people that can't break down the folic acid, it can actually stay in your body and this has become a matter of concern. It's now been given an official name unmetabolized folic acid syndrome. It can be found in the umbilical cord and infant blood, and we actually don't know the extent of the syndrome and its impact on the baby and the health moving forward.

Speaker 1:

So why put your body through all this work when you can just take the 5-methyltetrahydrofolate without the need to use the methyltetrahydrofolate reductase? And I want to say one thing too. So if your doctor recommends folic acid and says that folic acid has been shown to be effective in reducing the risk of neural tube defects and that's because most, if not all, the studies have been done using folic acid, since it's heat stable and it's very cheap to make, and using folate is way more expensive so your doctor is not wrong. But if she says that folic acid is better than folate, then that's wrong for all the reasons that we just mentioned before.

Speaker 1:

Now the big question is should you test for the MTHFR genetic variant? It's not part of the routine fertility workup. In fact, even if you had multiple miscarriages, not all the doctors would test you for this variant. I had a patient who went through five miscarriages and her doctor never tested her for the MTHFR. Oh, that's such a mouthful, because her homocysteine levels were always normal. But it turned out she did have this genetic mutation and as soon as she was treated properly, she went on to have two healthy pregnancies.

Speaker 1:

I have tested patients before using a very inexpensive saliva test and discovered that she had the homozygous MTHFR mutation. So I'm glad that we discovered this and we made sure that she was taking enough folate and also that her doctor was aware of this, so when she gets pregnant it can be managed properly, given that methylation is so critical during the embryo development in the first trimester and this is another reason why I just recommend folate anyway because the remedy for having this gene mutation is just to take the folate the 5-methyltetrahydrofolate. I typically recommend 600 to 800 micrograms of folate the 5-methyltetrahydrofolate. I typically recommend 600 to 800 micrograms of folate for pre-pregnancy and during pregnancy. It's a very safe supplement since it's water-soluble, so you're not at risk of accumulating it. All right, fertile friend, we're at the end of the episode here.

Speaker 1:

I want to circle back to the beginning, when my patient made a comment about how she didn't methylate. Well, there are tests that can determine whether or not this is indeed the case. I run a few tests that can determine where the nutritional deficiencies are and how exactly methylation is affected. These tests are very expensive and even though they do give you some really cool information and suggestions on which nutrients to supplement. The simplest remedy short term is just to make sure that you're using a high quality folate, but the long term remedy most likely is to make sure that we're influencing DNA methylation and methylation positively by managing environmental factors like diet, lifestyle, stress, toxin exposure.

Speaker 1:

I'm curious to hear about your thoughts on this. If this is the first time you're hearing about methylation or if you have any questions about it, please let me know. You can find me on Instagram as Dr Adrienne Wee or you can send me a text through the podcast directly. I would love to hear from you. Thank you so much for spending some time with me today. Fertile friend, until next time, take care of yourself and your amazing body. You are one fertile cycle away from getting pregnant.