MTHFR – The Common Genetic Mutation with a Big Impact - PCOS Diva
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MTHFR – The Common Genetic Mutation with a Big Impact

folates folic acidGuest post by Angela Heap

Updated May 2020

MTHFR is a gene. It stands for Methylenetetrahydrofolate reductase (MTHFR). Details about this it and the sheer importance it has to our survival have only emerged in the last 10 years, the result of finally mapping our genes as part of the Human Genome Project. But if you have PCOS, you should pay careful attention since it has real implications for your health and fertility.

What if there was a way to find out if you had fertility issues and also had a history of certain disease patterns in your family and hadn’t put two and two together? Wouldn’t you want to dig deeper to see if there really was a genetic reason behind some of your reproductive issues and what’s more, try to look into how to improve this? When the Gemone Project first started mapping all our genes in the 1970s it was thought that our genes were our blueprint and whatever we had inherited was our lot. Nowadays, we know that 30% of disease may be linked to genetic inheritance, 70% is the environment.

Powerful stuff!  We are nearer to the movie Xmen than you think, as 1 in 4 of us will have some form of polymorphism (mutation) that may or may not predispose us to a higher risk or chronic disease should we be complacent with our health. Your genes can’t be changed, but your environment can. This emerging field in Functional Medicine is called Epigenetics and relates to how your environment, your diet and your lifestyle choices can actually affect your health and actively turn on and off genes. Epigemonics relates to how to you can work around these issues and improve our situation, if in fact you do have mutations. Some would say it seems almost like an Aldous Huxley novel and that finally being able to identify your own genetic code, your “blueprint”, means you are transported right back to your ancestors clearly showing our DNA hasn’t changed much in over 100,000 years. Its easy to forget how primal we are and when we look into genetics it’s a stark reminder that we aren’t as modern as we think!


Genetics 101

In order to delve into MTHFR it is often a wise move to talk about the basics of genetics at this point, to set the scene.To make new cells, an existing cell divides in two. But first it copies its DNA so the new cells will each have a complete set of genetic instructions. Cells sometimes make mistakes during the copying process – kind of like typos.These typos lead to variations in the DNA sequence at particular locations, called single nucleotide polymorphisms, or SNPs (pronounced “snips”).

Some of these variations are functional like for eye color, some have little or no impact, and others can cause devastating health issues and down the line these impacts can lead to fertility problems.

Out of the huge array of genes we are faced with, there are about 30 or so genes that have a major influence on chronic health issues and around up to 10 of those will indirectly effect fertility (MTHFR being one of them) .

These genes are mostly related to methylation which is a fundamental pathway in the body involved in gene expression, detoxification, RNA regulation, protein function and many other biochemical processes. In this way, methylation underlies aging, digestion, inflammation, energy production, immunity and more. As reproduction is a key to all of these functions it’s important to get these right or we may have difficulties reproducing or carrying babies to term.

What is MTHFR and What Does It Do?

Studies began to emerge about MTHFR and linking it to many vital systems in the body from around 2005. It is one of the most widely researched mutations.

In short, MTHFR provides instructions for methylating – (either donating a methyl group or taking one away in the body for it to function). In order to keep the cycle going, the folate (or folic acid) you eat has to be converted via many steps to the active folate 5-MTHFR (5,10-methylenetetrahydrofolate (folate/folic acid/vitamin B9) to 5-methyltetrahydrofolate (methylated folate).

However, there is a problem. Many people test positive for the MHFR mutation, which means that in some cases they have a 70% loss of function of this gene.

Many of us are systematically ingesting folic acid via processed food or supplements, and by consuming this, instead of helping to support DNA replication, it will occupy the receptor sites in many people with the mutated gene and not allow this to cross the blood brain barrier for the substance to be used, further reducing the genes capacity for vital DNA transferation to happen, in effect slowing their bodies ability to grow and repair. Over time, chronic health issues may not be far away.

Folate is an important nutrient for fertility and sustaining life! It’s part of the raw ingredients needed for DNA to work.

So, if you have a mutation in the gene then its going to affect how much active folate you have available to help replicate and support a growing fetus as even your own cell replication is suffering here!

If you want to look into this further – folate breakdown is part of something called the methylation pathway or cycle where other co-factors come into play such as lipids, B12, B6, amino acids and their metabolites. There is an excellent explanation of this here. There are currently a total of 34 mutations in MTHFR. The MTHFR gene sits on Chromosome 1. There are two key variants that are tested for as at this stage there is little or no research on the others.What’s Wrong With Folic Acid?      

I want to put the folic acid issue in context now which I mentioned earlier. In the 1970s, studies into soaring spina bifida and Neural Tube Defects (NTDs) had a ‘eureka’ moment and decided the key to solving all these issues was to add synthetic folic acid to the mass population through food. So, in the late 1980s it was decided by public health officials in the US, Canada, and Australia as well as a number of other countries, that folic acid would be added to all baked goods, cereals, and bread as a mandatory measure. (1) The UK was cautions due to scientific reporting of higher incidents of colorectal cancer being seen with isolating folic acid. Manufactures in the UK do add folic acid to some food and contrary to popular belief it is not mandatory.(2,4) After  this issue was reported in medical journals from around 1993 many doctors and midwives started advising women of childbearing age to take folic acid, to help improve what  they saw as more children being born with NTDs.

As I mentioned above, folate is an important base ingredient for our vital DNA replication, but needs to broken down at least 5 times before its available in the active form of 5 MTHFR.

Folic acid is right there at the bottom of the pile in terms of getting broken down to a usable form for the body. Today it is widely used for the ‘preconception’ pack to potential mothers, is a synthetic formulation of a natural substance and in an ‘inactive’ state and, in short, many people with MTHFR mutations may not be able to break this down and convert it to the active 5-MTHFR in their bodies. In this instance, giving folic acid  to people who have polymorphisms  around MTHFR may cause an even worse situation and may also not solve the issue of NTD or spina bifida. NTDs are a result of the mother not getting enough folate to the growing fetus and can result in fetuses not fusing the cord and spinal connection around this. ( 3)

Some hematologists when they do in fact test for MTHFR and get a positive, suggest even higher doses of folic acid, which shows a fundamental misunderstanding of how to use nutracuticals to support the MTHFR gene. In short, this further clogs up the methyl pathway and causes issues all over the body.

What Can You Do To Overcome a MTHFR Mutation?

As many as 1 in 4 people have mutations to the MTHFR gene and so having the inactive form folic acid is like pouring oil on an already growing fire. So, for now I suggest eating natural folate as nature intended until you get the chance to test and see what’s going on. Here are some natural forms of folate that each give you around 100mcg of  folate. Having a few of these daily will give you lots of ‘real’ folate that is already in the active form. Also remember that cooking destroys folate, so I find a smoothie with some of these ingredients can help you get your daily requirements of folate. However things like beans may be a little harder to digest uncooked!

  • 1 cup Brussels sprouts
  • 1 cup cooked collard greens, mustard greens, or green peas
  • 1½ cups cooked broccoli
  • 5 spears asparagus
  • ½ cup cooked spinach
  • ½ cup avocado
  • 1½ cups shredded romaine lettuce
  • 2 ounces sunflower seeds
  • ¼ cup cooked lentils
  • ½ cup cooked black beans, kidney beans, or chickpeas

When you choose a multivitamin or prenatal supplement, be sure it contains folates and not folic acid. PCOS Diva has an excellent choice for each. 

Also, be a good health detective and don’t eat anything processed. Chances are its been bleached, deodorized, and all the nutrients stripped out of it so they have to then add them back in in a synthetic form – and that’s when you see things like folic acid in juices, milk, breads, and other goods. It is also worth noting it’s not just about the ladies. Partners/husbands/boyfriends or sperm donors also play a huge part in this as they give the child 50% of its DNA, so they have to look into this also.

We have so many genes, so how can we know which ones to focus on fertility? There are a few doctors, biochemist, naturopaths, and a pioneers in the field of Nutrigenomics, but this truly is a new area, and sometimes even physicians are new to this, so you may need take your newly found knowledge along with you to your doctor’s office.

Further information

  • The guru on MTHFR is Ben Lynch ND, he has extensively researched  MTHFR and is a cell and molecular biologist. He presents and talks about MTHFR internationally.
  • Amy Yasko MD works in and around MTHFR from the perspective of chronic health issues and a son with Autism.
  • Visit the Facebook page  set up by Sterling Hill who was a patient of Dr Ben Lynch with MTHFR and has now set up the support page for all to share in this journey. There are often comments pertaining to fertility and miscarriage on this site.
  • Visit my website if you want a little bit more information on genomics before you jump down the rabbit hole into a full on genetic analysis. You are welcome to download my free report on this:


Harvard School of Public Health.

Bland J. Systems biology, functional medicine, and folates. Altern Ther Health Med. 2008 May-Jun;14(3):18-20. Review.

Center for Disease Control (CDC). IMMPACT Project.

Lightfoot TJ, Barrett JH, Bishop T, Northwood EL, Smith G, Wilkie MJ, Steele RJ, Carey FA, Key TJ, Wolf R, Forman D. Methylene tetrahydrofolate reductase genotype modifies the chemopreventive effect of folate in colorectal adenoma, but not colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2008 Sep;17(9):2421-30.

Greenberg, James A, and Stacey J Bell. “Multivitamin Supplementation During Pregnancy: Emphasis on Folic Acid and l-Methylfolate.” Reviews in obstetrics & gynecology vol. 4,3-4 (2011): 126-7.


Angela OrangeAngela is a qualified Nutritional Therapist graduating from the College of Naturopathic Medicine in London after 3 years of intensive studying and 200  hours under Australian Naturopaths in a clinical setting. She is a member of BANT which is a regulated body through the British Association of Nutritional Therapists ( BANT).

Angela set up Fertile Ground Nutrition many years ago as a response to an overwhelming amount of clients coming to her with issues around conception and miscarriage. She specialises in fertility, hormonal management, pregnancy, baby and child health treating many UK and international clients. As a practitioner she applies a mixture of Naturopathic principles and a functional, diagnostic and scientific approach to food and nutrients.

Over the last 6 years Angela has strengthened her development and knowledge of fertility by honing her skills and diagnostic tools, focusing heavily on genetics as the key that opens the lock to infertility. Digging deeper into this area she completed training on genes, epigenetics and using DNA testing to help add the final piece to the puzzle of ‘unexplained infertility’. Angela applies her expert knowledge gained from this training to develop tailored and structured programmes for each individual client which, to date, have helped many with long term infertility to deliver healthy babies.  Angela had an 80% success rate in 2013 which she hopes to continue in 2014.

Angela also works closely with a number of internationally renowned experts in the field of fertility and is part of a global network of practitioners that work around using DNA analysis, which ensures she has a wealth of cutting edge knowledge at her finger tips which she applies directly to each and every client. Angela is a lecturer at the College of Naturopathic Medicine, with a particular focus on fertility and child health.  She also regularly speaks as part of the Fertility Question Time; the largest free fertility event online in the world, where she will be talking as part of the team with The Natural Fertility Expert UK time 8pm on May 29.  For more information on Fertile Ground Nutrition visit 


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  1. Hi Amy – great article. 23andme tests for the MTHFR mutation. The website also has message boards where members can ask each other about their experience and knowledge of MTHFR. I highly recommend the test ($99 covers hundreds of genetic tests).

  2. This is really informative, thanks! I have a question. I take a food-based pre-natal vitamin (New Chapter) so it has folate, instead of folic acid in it. Is that as good as eating foods with folate in them? I try to eat lots of those also, but just wondering if the vitamin helps too.

  3. Hello:
    Thank you for this article. It has tons of great information.

    As I was reading I was confused by the section related to the suggested foods to provide folate:
    “Also remember that cooking destroys folate, so I find a smoothie with some of these ingredients can help you get your daily requirements of folate. However things like beans may be a little harder to digest uncooked!
    1 cup cooked collard greens, mustard greens, or green peas
    1½ cups cooked broccoli
    ½ cup cooked spinach
    ½ cup cooked black beans, kidney beans, or chickpeas”

    In the paragraph above it states that cooking will destroy folate, however the foods mentioned several suggest cooked versions.
    I would just like to confirm if the foods should be left raw or cooked. As the article states, the beans would be hard to digest uncooked, but I question the things like the spinach and broccoli.
    Any information that you can provide will help

  4. Hi, I was diagnosed with PCOS in 2009 and just been diagnosed with 2x C677T MTHFR genes as well (in December 2014) due to having 2 seperate miscarriages following IVF. Is it possible that my MTHFR has caused my anovulatory PCOS, (and the inability I have to get pregnant when I do ovulate – without IVF?) – or are these really two separate issues?

    1. Your question is excellent, but specific. You may want to consult an expert in this field. I suggest Dr. Ben Lynch; he is the expert on MTHFR (