In New Zealand recently folic acid has hit the headlines as the government is considering adding it to flour for bread making to help prevent neural tube defects in unplanned pregnancies. This is not great news for many females trying to get pregnant and I will explain why in this blog post. This is another reason why it is a good idea to be gluten free if you have fertility issues.
Over the last 6 years or so there has been a lot of emerging research available about the negative effects of folic acid and how if you are trying to get pregnant supplementing with active folate (methylfolate) is the preferred choice. This is due to a MTHFR gene mutation that affects as many as 50% of the population. If you do have a mutation in your MTHFR gene, your body is unable to convert synthetic folic acid into its active form 5 – Methylenetetrahydrofolate (5-MTHFR) via the methylation cycle. What this means is there is less active folate available even if you are taking high doses of folic acid. It also means that the large doses of folic acid are ending up as unmetabolized folic acid in the bloodstream, which can block the methylation cycle and isn’t ideal for our health.
Yet despite this information being available, there are still some fertility clinics supplementing a whopping 5mg of Folic acid. Why is this message not getting through? According to a study publishes in the Journal of Assisted Reproduction and Genetics in 2018 (1) `The conventional use of large doses of folic acid (5mg/day) has become obsolete. Regular doses of folic acid (100-200mg) can be tolerated in the general population but should be abandoned in the presence of MTHFR mutations, as the biochemical/genetic background of the patient precludes a correct supply of 5-MTHF, the active compound’
It can be quite complex and confusing to understand all this so I will try and explain it as simply as I can. It is so important that you are aware of this as this could be affecting you.
What is folic acid and why is it detrimental for fertility for some people?
Folic acid is a synthetic man-made form of vitamin B9 that is not found in nature. It must undergo various conversion steps in the methylation cycle to become active folate (known as methylfolate or 5-MTHFR) a form that is utilised by the body and is important for healthy DNA. Methylation is a simple biochemical process that involves the transfer of a methyl group (1 carbon atom and 3 hydrogen atoms) from one substance to another. The most important methyl groups used in methylation are methylfolate (5-MTHFR), methylcobalamin (active B12), Pyridoxal 5’- Phosphate (active B6), and choline. The issue is that if you have the MTHFR gene mutation, which roughly 50% of the population has, then the conversion to folate is disrupted as the MTHFR enzyme (methylenetetrahydrofolate reductase) affects the last step of the methylation cycle.
If you eat foods rich in natural folate such as leafy green vegetables, it is already in the form of methylfolate (active folate). However, if you eat foods fortified with synthetic man-made folic acid such as bread and cereals, then the folic acid can’t be used until it has gone through all the conversion steps down the methylation pathway until it gets to methylfolate (5-MTHFR). This means that despite eating plenty of folic acid (and even taking supplemental folic acid) your body remains deficient in folate if you have the MTHFR gene mutation.
The problem is that even a little bit of folic acid from food can disrupt the methylation cycle, which is why the fortification of flour with folic acid could be problematic for some people. It is important to avoid all forms of folic acid from fortified foods and supplements and only take methylfolate (active folate) and eat folate rich foods like leafy green vegetables every day.
According to Dr Ben Lynch (2018) `Because folic acid resembles folate, it gets into your folate receptors, where it blocks natural folate from getting where it needs to – inside your cell. As a result, if you are eating more foods containing folic acid than leafy green vegetables, the naturally occurring methylfolate struggles to get into your cells. And without enough methylfolate, your body can’t methylate. In this way, folic acid blocks methylation’
Why is active folate so important?
As Folate is one of the most important nutrients for fertility, being deficient in active folate can affect your ability to conceive and increase your chances of pregnancy complications and recurring miscarriage.
Folate is needed for the development of red blood cells and DNA production. It plays an important role in cell division, so is important for both egg and sperm health.
Folate helps to support ovulation and progesterone levels and is important for methylation, an important phase 2 liver detoxification pathway.
Folate helps to prevent neural tube defects, congenital heart defects, cleft lips, limb defects, and urinary tract abnormalities in developing fetus.
A deficiency in folate increases the risk of premature babies, low birth weight, and fetal growth retardation. A deficiency may also increase homocysteine levels in the blood, which may lead to miscarriage.
Some typical deficiency signs of folate are fatigue, poor immune function, poor digestion, anemia, canker sores in the mouth, tender swollen tongue, low mood, pale skin, premature grey hair.
It takes about 3 months to re-establish folate levels after taking the contraceptive pill (which depletes levels), this highlights the importance of a 3-month preconception care plan before trying to conceive.
Leafy green vegetables are the best source of natural folate and are easy to include in your diet daily. Examples are kale, spinach, broccoli, silverbeet, brussels sprouts, mesclun, romaine lettuce, mustard greens, and rocket. Other food sources are lentils, liver, rice, asparagus and avocado, sweetcorn, oranges.
It was about 4 years into my 10 year infertility journey that I first found out about the MTHFR gene and I often wonder whether taking folic acid for the first few years had a negative impact on me. It was Dr. Ben Lynch who introduced me to the concept of MTHFR when I listened to one of his podcasts. The science was very new and confusing at times and even though I started taking active folate rather than folic acid, I still took a prenatal multi that had folic acid in it out of ignorance. This was because the research was very new and at the time there weren’t any prenatal multivitamins with activated folate on the market. This has changed now thankfully and there are many prenatal multivitamins on the market, my favourite being the Naturobest range or Thorne Research Prenatal Nutrients.
It was a few years later that I finally eliminated all folic acid from foods and supplements and a few months later I found out I was pregnant at the age of 43 after 10 years of secondary infertility. It wasn’t the only change I made at the time but I do believe that removing all folic acid had a contributing factor.
I never got around to testing for the MTHFR gene, mainly because it was new science on the scene and while I was trying to conceive the only testing was expensive genetic testing from places like 23andme. This has all changed now and you can get a MTHFR gene mutation test done fairly easily through various companies in New Zealand, one of those being i screen NZ, a health screening service that can be accessed by the general public.
During the last few years of my fertility journey, my approach was that if roughly 50% of the population had the MTHFR gene, then I was likely to be one of them as I had a history of infertility and recurring pregnancy loss, and so I am going to act as if I do have the MTHFR gene mutation in terms of my diet, lifestyle and supplement regime. When I conceived my supplements included a prenatal multivitamin with active B vitamins including folate and not folic acid, an additional supplement of 5- Methylenetetrahydrofolate (active folate) and Methylcobalamin (Active B12) because my B12 was low. A healthy methylation cycle involves the teamwork of both Folate and Vitamin B12 so I made sure I took optimal levels of both.
I do encourage you to take advantage of the testing options that are available now, however, If you are not able to go down the testing route, then I would encourage you to act like you have the MTHFR gene mutation as well, especially if you have a history of unexplained infertility, recurring pregnancy loss, and low thyroid function. ‘People experiencing fertility problems and recurrent miscarriages have a strong likelihood to have the genetic variant that makes folic acid supplementation essentially useless – and that use of active folate in the form of 5-MTHF is beneficial’ (2)
As well as eating leafy green vegetables, avoiding foods with folic acid and taking a prenatal with active folate (plus an additional folate supplement), you can also support your methylation cycle by:
Eat a clean whole foods diet, organic where possible
Reduce refined sugar and processed foods
Support your gut microbiome and digestive health
Eliminate food sensitivities and inflammatory foods
Reduce your stress levels where you can
Where can I find more information about the MTHFR gene mutation?
I have really just covered the basics in this blog, in relation to fertility issues. There is so much more reading you can do if you want to find out more about the MTHFR gene. Dr. Ben Lynch is the leading expert on MTFHR and has lots of information available on his website (www.mthfr.net) including a video course you can sign up to. I also recommend his book Dirty Genes which is a very helpful resource.
So, in summary, if you have a history of infertility, recurring pregnancy loss, and thyroid issues or you feel you might have the MTHFR gene mutation, then I would strongly recommend:
Get tested. Please get in contact if I can help you with this
Get rid of ALL folic acid and change to methylfolate (5-MTHFR). Check all your supplements
Take a prenatal multivitamin with activated B vitamins and NO folic acid
Take an additional supplement of 5-MTHFR so you are taking at least 800mcg of Folate per day, although some people may need more than this. If you are unsure work with a practitioner.
Act like you have the MTHFR gene mutation in terms of your diet and lifestyle.
(1) Servy E J et al MTHFR isoform carriers. 5-MTHF (5-methyltetrahydrofolate) vs folic acid: a key to pregnancy outcomes: a case series. J Assist Reprod Genet 2018 Aug;35(8):1431-1435, Jun 7
(2) Lynch Dr Ben, Dirty Genes (2018), P 48, Harper One.
(3) Gray N, Could Active Folate boost IVF chances. Fertility Study backs 5-MTFHR over Folic acid 13/7/18 www.nutraingredients.com/article/2018/07/13