In my current series of preconception webinars, I am not surprised by the number of women joining me who have had multiple miscarriages or who are currently having IVF (often unsuccessfully). They didn’t know they had the MTHFR gene and even after multiple pregnancy losses, still were not checked for the gene. Eventually, they sought the answer themselves.
Folic Acid Supplements in Fertility Treatments
Folate is critical for DNA methylation and cell division. As a result, it’s also important for the proper development of ova, or egg cells, that can successfully implant in the uterus.
But when we say folate what do we mean?
Well, think of ‘folate’ as an umbrella term. Under that umbrella, there is folic acid (the synthetic man made form), folinic acid which is an important cofactor for healthy DNA creation, and our active folate, called5-MTHF (methyltetrahydrofolate).
In IVF and fertility issues, doctors and specialists alike are still recommending a high dose 5mg folic acid supplement to remedy a MTHFR mutation.
We also have mandatory folic acid supplementation in all our commercial bread and in many of our breakfast cereals, juices, protein bars, shakes, and energy drinks. So researchers are now looking into what these high doses are doing to us.
You all know that those with the MTHFR gene mutation are counseled into avoiding folic acid. The reason is that folic acid has the potential to build up and inhibit our DHFR enzyme, which is crucial in our folate pathway. Some research has also shown that unmetabolized folic acid builds up and affects our immune system negatively too.
But now we know more! Some really interesting studies on folic acid were released in the latter half of 2015 that specifically focused on folic acid. These studies looked at the 5mg dose of folic acid to see how it affected fertility. Now, this is interesting to me, because many of our patients in the clinic have been prescribed 5mg of folic acid in response to their doctor seeing a MTHFR C677T homozygous result, or to prepare their body before they start IVF cycles.
So let’s take a closer look:
We know that fertility is decreasing world wide and we have to ask ourselves why. Sure we have a more toxic environment than ever before; yes we are more stressed than previous generations and have worse diets and fewer nutrients in our soil. But a recent study completed in the Human Molecular Genetic Journal at the end of 2015 showed some interesting information. They looked at DNA methylation of the sperm when they gave folic acid. The researchers trialed 5mg of folic acid in infertile men and acknowledged that serum folate concentrations increased significantly after 6 months of folic acid supplementation. They also noticed a slight, but non-significant increase in sperm numbers, but the surprising thing is that they found a ‘significant loss of methylation across the sperm epigenome’, and more so if you were homozygous for the MTHFR C677T mutation.
What is more alarming is that the researchers suggested that this loss of methylation in sperm DNA might be transmitted to the offspring. So what they are saying is that folic acid at high doses not only decreases the fertility of men by negatively affecting their DNA, but also that these effects may be passed onto the child.
Is this significant? Could this be adding to the infertility effect we are seeing in men?
In the Clinical Journal of Nutrition in 2015, Karen Christensen found that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo MTHFR deficiency in mice.This deficiency affects liver cells ability to metabolize fat and affects cell membrane integrity. That’s why we often see elevated cholesterol levels in people with MTHFR deficiency and issues with egg integrity in women undergoing IVF.
Another study looking at folic acid supplementation in people with the MTHFR gene going into IVF also revealed some interesting data. This Swedish study found that the higher the folic acid intake, the higher the plasma folate. Overall, the conclusion was that ‘high folic acid intake did not seem to assist infertile women to achieve pregnancy after fertility treatment’.
It’s the same result as above for the men.
So we seem to be getting more of the same. Yes, folic acid is going to increase serum folate levels, that much makes sense. However, it does not help DNA methylation, that’s why it’s not helping fertility.
Methylation of DNA is what controls our fertility. Just because we’ve always done something doesn’t make it right. There should be a worldwide review of folic acid supplementation in fertility treatment. There is enough research emerging to have a review of existing protocols.