Folate and Fertility

Folate and Fertility

Folate is a B vitamin otherwise known as B9, it has an essential role during the early stages of pregnancy to reduce the risk of neural tube defects such as spina bifida. Deficiencies in folate have also been associated with infertility and miscarriage. It is recommended that women take folate from 3 months before conception until the end of week 12 of pregnancy.

Folate is an essential vitamin that cannot be made by the body so adequate amounts must be obtained through diet or supplementation. The body’s demand for folate increases during pregnancy as it is required for the growth and development of the baby, this makes supplementation of folate essential to meet these high demands of early foetal development. You not only want to make sure you are getting enough folate to support pregnancy, but you also want to make sure you are able to absorb it effectively.

You may have heard about folic acid, folate and methylfolate, and be a little confused as to which one you need and which is which.

It is important to note there are key differences between these three forms of folate. Folate, in many different forms (both active and inactive), occurs naturally in foods such as green leafy vegetables, eggs, and legumes. Folic acid is the man-made, synthetic, version of folate, and is inactive. You will not find folic acid in natural whole foods, you will only fid it in supplements and fortified foods - like bread in NZ.

Methylfolate (5-MTHF) is the active form of folate/B9, here it is the “methyl” part of its name that becomes important, this acts like a carrier for folate to get into the cell and exert its effect, this means that methylfolate is ready to freely move into the cell without having to wait around for its carrier to let it in which may or may not appear depending on your genes.

Folic acid needs to wait for a methyl group to come along and carry it into the cell. 


A simplified way to think of it:

Think of the methyl group attachment as a ticket to the party

Nutrients that have the ticket can move into the cell and go to the party. 

Nutrients that don't have a ticket need to line up outside and wait to be let in by the bouncer and given a ticket.

Most supplements will contain folic acid, or you may have been given folic acid by your GP, some higher quality supplements will contain methyl folate too.

Folic acid needs to be converted into methylfolate, remember it needs its carrier to enter the cell before it can be utilised. This is where you can run into problems.

Your genetic makeup dictates how well you can convert folic acid into the active form methylfolate. It is estimated up to 60% of the population have a gene variation on their MTHFR genes which control the production of the enzymes needed for methylation of folic acid. These genes impact how well your body can convert inactive folic acid to active and useable methylfolate, if you are one of the 6 in 10 people that have this gene mutation it is possible you are not absorbing folic acid effectively.

Testing for this gene mutation can be done, however I like to safe-guard my patients by always using the most active form of folate; methylfolate, to ensure they are absorbing what they need regardless of their genes. The active form of folate - methylfolate can come under different names, for the active form look out for: 5-MTHF, 5-Methyltragydrofolate, or L-Methylfolate (not folic acid).


But, what about the research into folic acid for neural tube defects?

It is true that large studies have proven that folic acid prevents neural tube defects. This study was carried out in the early 90's before there was an understanding of methyl folate or the role of MTHFR genes. 

We know the following about methylfolate:

  • It needs no conversion or activation in the body
  • It is the most abundant form of folate in natural food
  • It is the main type of folate in our blood
  • It raises blood levels of folate better than folic acid in all people, including those with MTHFR variations

Given our current understating of folate and how it is processed in the body, if the same study was to be done today it would use methylfolate. However, in the world of health, money talks and methylfolate is very expensive compared to folic acid. Not only would large scale studies be very expensive, but government lead supplementation programs would also be more expensive. 

In NZ, the current cost of folic acid for most is a $7 script charge for enough tablets to last the first 12 weeks of pregnancy - this works out to be $0.08 per day, but the actual cost of the tablet will be far less. 

The cost of methyfolate tablets is $0.35 per day, a cost that will need to be covered by the individual and is not funded by government healthcare. 


This is just the tip of the iceberg

I have given a very simplified version of the folate and MTHFR gene research and it's impacts on fertility. It is a complex topic and one that will effect each individual differently, please make sure you are getting advice on this topic from someone who is not only qualified but up to date on the latest research.

The intricacies of different vitamin forms and which is best for each health situation is what qualified nutritionists specialise in. Before buying supplements online or over the counter it pays to check in with a qualified nutritionist to make sure what you are buying is right for you. For a 15-minute supplement review to discuss your needs, click here.


References - further reading:

Greenberg JA, Bell SJ, Guan Y, Yu YH. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol. 2011 Summer;4(2):52-9. PMID: 22102928; PMCID: PMC3218540.

Recber, Tuba, et al. “Metabolic infrastructure of pregnant women with methylenetetrahydrofolate reductase polymorphisms: A metabolomic analysis.” Biomedical Chromatography (2020): e4842.

Plumptre, Lesley, et al. “High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood.” The American journal of clinical nutrition 102.4 (2015): 848-857.

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