In this week’s article I will explain why folic acid is so important when trying to conceive and in the early stages of pregnancy, the importance of a process called ‘methylation’ and how it relates to folic acid, and how a genetic defect called MTHFR affects methylation and the body’s ability to use folic acid. I will also give advice on testing for MTHFR and what you can do to minimize its effect so you can conceive naturally.
Why Do I Have To Take Folic Acid?
When you are trying to get pregnant, one of the first pieces of advice you are given is to make sure you take folic acid. We all know it’s important, but why is that? Well, when we talk about fertility the most important thing to consider is your genetic makeup or code. Your genetic code is contained in your DNA which is very susceptible to coding errors that cause genetic defects. DNA is of vital importance in fertility both in the health of the egg and sperm as well as for the newly developing embryo. The whole reason folic acid is added to prenatal vitamins is because of its role in the replication of DNA. When the egg is fertilized, and has implanted in the uterine lining, the embryo begins a process of rapid cell division, this rapid cell division uses a lot of methylated (or active) folic acid – what is known as methylfolate.
What Is Methylation and What Does It Have To Do With Folic Acid & Fertility?
Let’s start with a simple biochemistry lesson. Methylation is the process of effectively turning genes off or on by adding methyl groups to the strands DNA. A methyl group is a cluster of a single carbon molecule and three hydrogen molecules that methylate another molecule by attaching to it.
Basically, wherever there is a methyl group, the gene it is attached to will be silent and, when the methyl group is removed, the gene will be expressed. The concept is simple but the effects are significant in terms of our susceptibility to any disease or health condition that we carry. For example, women with methylation defects have an increased risk of blood clots in pregnancy.
Methylation is responsible for making, repairing and maintaining DNA (our genetic code) which is of vital importance for fertility but in addition to this, it also manages or contributes to a wide range of crucial bodily functions, including:
- Estrogen and testosterone regulation
- Immune regulation
- DNA maintenance
- Energy production
- Mood balancing
- Inflammation regulation
Having an optimally functioning methylation cycle is key to reducing your susceptibility to cardiovascular disease, cancer, neurological disease, infertility and miscarriages. A good guideline is for that for each genetic defect you carry there is a 33% reduction in your body’s ability to methylate. If you have 2 defects, that percentage doubles
Around 40% of the population carries at least one genetic mutation on a methylation gene and there is one in particular that has been extensively researched – MTHFR, or methylenetetrahydrofolate reductase.
So why does it matter if you have a MTHFR defect? It matters because the ability to convert the vital nutrient folic acid into its biological active form, 5-methyltetraydrofolate (5-MTHF), is a methylation–driven, biochemical process. If you don’t have the ability to methylate, or your methylation is impaired, your ability to turn folic acid into its active form is reduced. If you don’t have the converted form of folic acid – 5MTHF then the genetic coding of your DNA may not replicate properly which creates a risk DNA defects in the embryo. DNA defects lead to infertility and miscarriages.
The only way to find out if you carry methylation defects is to be genetically tested – for fertility, I recommend both the mother and father be tested. Genetic testing can be done with saliva or blood although blood testing is more expensive and most health insurance do not consider the testing medically necessary and therefore will not cover the testing which can make blood testing for genetic markers cost prohibitive.
Most practitioners recommend the 23andme genetic testing – a simple and cheap saliva test. At the time of writing, you can run a full methylation genetic test for just $199.
When you get your results, the first thing to do is see if you carry a methylation defect. There are two main genes to look out for – MTHFR C677T and MTHFR A1298C. These are the genes related to methylenetetrahydrofolate reductase (MTHFR) and are commonly referred to as the 5 Mother genes. The next thing to do is to determine if you have one copy (heterozygous) or two copies (homozygous) of the affected gene. The combinations are listed below, with the most significant first:
- MTHFR C677T – homozygous – Listed as (+/+). This has a 70% reduction in methylation
- MTHFR C677T & A1298C – heterozygous – Listed as (+/-). This has a 50% reduction in methylation
- MTHFR A1298C – homozygous – Listed as ( +/+). This has a 30% reduction in methylation
- MTHFR C677T – heterozygous – Listed as (+/-). This has a 30% reduction in methylation
- MTHFR A1298C – heterozygous – Listed as (+/-). This has a minimal reduction in methylation
Please note: The test results are hard to read and, even when you use an online interpretive website like geneticgenie.com, it is best to have your Naturopathic physician review the data with you. They will also be able to advise you on the proper course of treatment for you based on your results.
Once you know for sure that either the mother or the father have a methylation defect oral supplementation with methylfolate (5MTHF) is necessary. However, a sudden rush of methylfolate if the body has been deprived of it for years can cause side effects such as increased muscle pain, anxiety, agitation, headaches and a host of other symptoms so it is often best to start by taking the active form of vitamin B12 (methylcobalamin) starting with a low dose (1000mcg daily) and gradually increasing up to a maximum of 5000 mcg before slowly adding methylfolate into your system.
The starting dose of methylfolate (5MTHF) is 500mcg/day working up to 1000mcg. The dose will be increased from there with some people going as high as 10 mg/day. If you have significant methylation defects you will need the assistance of your physician to help with dosing.
Although we talk about the importance of taking folic acid when trying to conceive, what we actually mean is folate. Folic acid is a synthetic version of folate that can be found in supplements and fortified foods. For people with significant mutations, consuming large amounts of synthetic folic acid can be toxic. However, it is safe to consume foods like leafy green vegetables that contain naturally occurring folate.
Please note: If you have the MTHFR C677T mutation, either heterozygous or homozygous, it is important to discuss with your physician if you should avoid all synthetic folic acid.
Example Treatment Protocol For Methylation Defects*
- Active Folate 5MTHF starting with 500 mcg and increasing to 1mg (1000mcg) over a few weeks. For higher dosing you should work with your physician to establish what is right for you.
- Methylcobalamin (a form of vitamin B12)- starting dose 1000 mcg
- Riboflavin (vitamin B2) – 30-90 mg a day
- Pyridoxial 5 phosphate (a form of vitamin B6) – 45-75mg a day
- Magnesium – 300mg a day
- Eat leaf greens
- Avoid gluten
- Avoid dairy
You should also try to eliminate toxins in your environment as much as you can. This would include reducing your exposure to chemicals like those found in cleaning supplies, paints, solvents, air fresheners, avoiding artificial dyes or preservatives in food and keeping alcohol and caffeine consumption to a minimum.
*Treating methylation defects can be complex so I recommend working with a naturopathic practitioner who can help tailor the treatment to you.
Nutrients Used to Support Methylation
In addition to having the MTHFR defect, what you eat can also have an effect on your ability to methylate. Key nutrients are necessary to turn the active form of folate into methylfolate – here is a list of vitamins and minerals required to methylate:
- Vitamin B2 ( riboflavin)
- Vitamin B6 ( pyridoxine)
- Vitamin B12 (methylcobalamine)
- Folate (Folinic acid)
Please note: You can buy all these products in my online pharmacy.
So again why does all this information about methylation matter if you want to have a baby? It matters because methylation defects can be the cause behind unexplained infertility in some couples – if you can’t methylate or you have a reduction in methylation then there is an increased risk for genetic mutations and therefore increased risk of infertility and miscarriages. Imagine that, just by addressing an underlying methylation defect, you can go on to conceive a healthy child naturally.
When you go to develop a fertility plan, understanding if you carry a genetic defect for methylation is a key factor in optimizing your fertility. With a simple saliva test you can check to see if you carry a defect. By supplementing with 5 MTHF – the active form of folic acid you can correct the underlying deficiency then, when you have an optimally working methylation process your body will regulate your hormones (estrogen and testosterone) better and your genetic replication and DNA works more optimally. Always remember that healthy bodies make healthy babies.
If you are interested in more information on fertility or testing your methylation genes please book an appointment!
Join me next week as I discuss the role of optimizing male fertility as part of my series on fertility.