Folate and Pregnancy

November 16, 2022

Folate and Pregnancy

November 16, 2022

Folate is one of those vitamins that we don’t really hear much about until we start trying to conceive. While folate is always needed to support health, it plays a specially important role during pregnancy, garnering it attention during this time.

However, folate actually has a fairly contentious history and is currently in the prenatal nutrition hot seat. So what is this vitamin, why is it important, and how should you be incorporating it daily?

What is Folate

Folate, also known as vitamin B9, is a water soluble B vitamin that is crucial in methylation. Methylation is vital to DNA synthesis, neurotransmitter production, detoxification, egg and sperm quality, estrogen metabolism and so much more. In other words, it is a key player in making sure our body is functioning optimally.

During pregnancy, folate becomes critical – adequate levels are needed within the first 3-6 weeks of life (before most of us even know we are pregnant) to help form the neural tube (think brain & spine), preventing neural tube defects (NTDs) such as anencephaly and spina bifida.

Low folate levels have also been associated with skipped ovulation, fertility challenges, and early pregnancy loss. High homocysteine levels, which are produced as a result of low folate, are also associated with vascular changes, which can impact the placenta. In other words, staying on top of folate when we trying to conceive or during pregnant is critical.

The History of Folate and Pregnancy

This connection between NTDs and folate deficiency was discovered in the 1960s, with research showing that 400-800 mcg of folic acid – the synthetic form of folate – could help prevent NTDs.

This discovery led to the US government mandate that enriched grain cereal products be fortified with folic acid. This country wide initiative was put into action in 1998 in an effort to boost up commonly consumed foods – such as white wheat bread and cereals – with folic acid to help people reach their daily dose. Since this initiative, there has been a decline in NTDs in the US, decreasing the prevalence by 19-32%.

However, emerging research on the metabolism of folic acid has highlighted some potential downfalls and further consideration that is needed.

Folic Acid, Folate, 5-MTHF, and MTHFR Mutations

Without getting completely bogged down by the science, it is important to recognize that there are multiple forms of vitamins. There is usually an an active form (the type that the body can actually use), inactive form (the form that must be converted to an active form to be used), and synthetic form (a vitamin that has been created in a lab for the use of supplements and vitamins).

With the case of B9:

  • Folate = inactive form that is consumed through foods
  • Folic acid = most common synthetic form that is in a majority of prenatal vitamins and that was a part of the government mandate. It is also an inactive version.
  • 5-methyltetrahydrofolate (5-MTHF) = active form that the body can utilize

MTHFR, short for methylene tetrahydrofolate reductase, is an enzyme that helps to turn folate into its active form 5-MTHF and is required to lower homocysteine levels by converting it into methionine and cysteine. In other words, MTHFR is important in considering whether our body is able to use folate.

However, research has shown that up to 40-60% of the population has a genetic mutation or variation of the MTHFR gene, influencing how our body utilizes folate. The most common variation, known as MTHFR C677T, is believed to impact more than 25% of those of Hispanic descent and up to 15% of all North American Caucasians. If you have this mutation, it is estimated that folate metabolism (i.e. usage) declines between 30-60%. So what does this mean practically?

It means that over half the population has an impaired ability to use synthetic folic acid and will likely require higher levels of folate and/or the activate form of folate, 5-MTHF. And why is this a problem?

Those with MTHFR variations are at greater risk for

  • pregnancy loss (read this, this & this but note that this still remains controversial and the exact relationship has not been established)
  • preeclampsia
  • higher homocysteine levels

and more. The other concern is that when those with a MTHFR variation consume folic acid, it may lead to a build up of this inactive form. Since the variation in the enzymes leads to the reduction of the body’s ability to convert folic acid into the active form, the accumulation of unmetabolized folic acid can interfere with methylation and lead to other consequences. Moreover, this accumulation can lead to detectable amounts of folic acid in the fetus, which may have impacts on baby.

“In light of our understanding of folate metabolism, there is growing concern about the risk to the fetus of high levels of inactive metabolites of folic acid, for both their oxidizing effects and a possible association with vitamin B12 deficiency. Instead, the administration of equimolar doses of 5-MTHF enables reaching the same target of maternal serum folate without generating inactive metabolites” European Journal of Obstetrics & Gynecology and Reproductive Biology

While the impacts of accumulated folic acid are still being understood, preliminary research has shined a light on the need for hesitation with widespread folic acid supplementation.

And even among those WITHOUT a MTHFR variation, taking 5-MTHF may be more effective than folic acid. While the jury is still out, one study did show that L-MTHF may be more effective at lowering homocysteine levels than folic acid. Research has also shown that 5-MTHF is less likely to mask a vitamin B12 deficiency (another article for another day) than folic acid.

All in all, research is mounting in support of 5-MTHF supplementation over folic acid supplementation.

What To Look For On Prenatal Vitamins

I have to note that *most* OBGYNs and conventional healthcare practitioners will still recommend folic acid over 5-MTHF in prenatals. Why? Well, it takes years and years for policy to reflect the research, and until it does, many healthcare practitioners will continue to go with the status quo.

Previous research has shown that folic acid is much more efficiently absorbed in the GI tract than even folate! However, it is important to remember that absorption does not = utilization. But these varying factors combined make healthcare providers more likely to support folic acid.

However, I am a big advocate that anyone who is trying to conceive or are currently pregnant should be opting for the active form of folate when possible. As such, I recommend that prenatals contain methylated folate, which can go by the names of:

  • L-methylfolate (L-MTHF)
  • L-5-methyltetrahydrfolate (5-MTHF)
  • 6(S)-L-methyltetrahydrofolate

And generally speaking, they contain amounts of 400 mcg or more.

There are a few prenatal supplements that I tend to recommend, however, it depends on each individual’s context. If you are interested in discussing this further and finding a supplement regiment that supports and considers you, book a discovery call now.

Where Else Can I Get Folate?

As with everything, we want to prioritize a food first approach. Regardless of whether you have the MTHFR variation or are trying to conceive, emphasizing foods rich in folate will be important.

Foods sources of folate include:

  • Animal liver
  • Eggs
  • Green vegetables like spinach, asparagus, broccoli, and seaweed
  • Sunflower seeds
  • Lentils, chickpeas, and black beans
  • Tahini

Remember That Folate Is Not The Whole Picture

When we consider the role of folate in preventing NTDs, we want to look at the mechanism behind it. While the precise explanation is not well understood, the general hypothesis is that it is due to the role of methylation. If this is true, we should also be considering all the other key players that assist folate with methylation, such as vitamin B12, vitamin D, methionine, glycine, choline, inositol and more.

Moreover, making sure to eat an abundance of fruits, vegetables, whole grains (not fortified with folic acid), legumes, lean protein and healthy fats will be more important in the prenatal health picture than a single nutrient.

Looking for more prenatal nutrition support? Contact me here.

Disclaimer: not intended to replace medical advice. For educational purposes only

Written by: Amanda Wahlstedt, RDN

Fertility + Hormones




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