MTHFR and the Folate Debate

Adequate intake of folate beginning at least one month prior to pregnancy is crucial in preventing neural tube defects (NTD), which are birth defects of the brain and spine. No one is debating the importance of this, as babies go through critical development in very early pregnancy.

Folate is a general term for the different forms of vitamin B9. Folate is found naturally in food but also has a synthetic form called folic acid. The debate happening right now is over which form of folate is best for preventing neural tube defects, especially for those with the MTHFR gene variant.

The MTHFR gene helps your body process folate. It ensures the right form of folate is available for building your baby's DNA and supporting their development. MTHFR C677T is the most common variant in the MTHFR gene. When consuming the same amount of folic acid (the synthetic form of folate), those with the MTHFR gene variant will have an average blood folate concentration (amount of folate in their blood) that is slightly lower than those without. 

Current Recommendations

Let’s explore current recommendations on folate. 

Recommended Dietary Allowance:

• Not pregnant (ages 14+): 400 mcg DFE
• Pregnant (ages 14+): 600 mcg DFE
• Lactating (ages 14+): 500 mcg DFE

In addition to the above recommendations (which is for folate found naturally in foods), a daily vitamin supplement that contains 400-800 mcg folic acid is recommended for those that are pregnant, trying to conceive, or that even have a chance of becoming pregnant. As stated in the Dietary Guidelines for Americans 2020-2025 publication:

The critical period for supplementation starts at least 1 month before conception and continues through the first 2 to 3 months of pregnancy.

Foods fortified with folic acid also help people meet this recommendation. Nutrition facts labels have recently been updated to help people understand which forms of folate are contained in specific foods and supplements. Read more on this at the link below:

🔗 Folate and Folic Acid on the Nutrition and Supplement Facts Labels | FDA

Important Notes:

• These recommendations are still appropriate and relevant for those with the MTHFR C677T gene variant.
• There is an established tolerable upper intake level (UL) for folic acid of 1,000 mcg, because it can mask a Vitamin B12 deficiency. This includes folic acid from supplements and fortified foods. There is no established UL for folate naturally found in food.
• Your care provider may recommend a higher amount of folic acid for those at high risk of having a baby with neural tube defects (like those who have had a prior NTD-affected pregnancy). 
• Recommendations may differ for those with more rare MTHFR gene variants. This does not include the very common MTHFR C677T gene variant.

Supplementing With Folic Acid vs. “Natural Food Folate”

There are individual health care professionals (and social media influencers) challenging current recommendations. 

Lily Nichols, RDN is one example. You can read more on her work and stance on this topic below:

🔗 Folate: Why It’s Superior to Folic Acid for Pregnancy (Even if You Don’t Have MTHFR) | Lily Nichols, RDN

One big reason for this debate surrounds the MTHFR gene variant and processing folate. It’s because of that slight reduction mentioned above. While there is so much misinformation on this topic, this slight reduction does not mean those with the MTHFR gene variant can’t process folic acid. The current recommendations are appropriate and for those with and without the MTHFR gene variant.

The alternative to folic acid supplementation being proposed is to use supplements containing “natural food folate” (in addition to the recommendations on consuming folate found naturally in foods). 

It’s important to be aware that “natural food folate” contained in certain supplements (such as 5-MTHF) is not the same as folate found naturally in foods. Like folic acid, it is also man-made.

Five Reasons To Trust Current Recommendations

Here are my five reasons to trust current recommendations.

1. General Consensus Among Relevant Organizations

Here’s a list of organizations who are standing by current recommendations:

• Academy of Nutrition and Dietetics
• American Academy of Family Physicians
• American Academy of Pediatrics
• American College of Medical Genetics
• American College of Nurse-Midwives
• American College of Obstetricians and Gynecologists
• Centers for Disease Control and Prevention
• March of Dimes
• United States Food and Drug Administration
• United States Preventitive Services Task Force

There are individual outliers who disagree, but general consensus is still in support of current recommendations.

2. Studies Have Proven the Effectiveness of Folic Acid Supplementation on Reducing Neural Tube Defects, Even Among Those With the MTHFR C677T Gene Variant

Current recommendations still stand because science supports them. Supplementing with folic acid has been proven to reduce neural tube defects. We have sound science backing the timing and amounts recommended. We know these recommendations work for those with the MTHFR C677T gene variant. 

We don’t yet have studies proving the effectiveness of supplements containing “natural food folate”. This doesn’t mean this isn’t an effective option. We just don’t know enough yet to change current recommendations. 

3. Difficulties in Meeting Recommendations for Folate Found Naturally in Foods

It is challenging for many people to meet the daily recommendations for folate found naturally in foods. This is why certain foods have been fortified with folic acid and why taking a supplement containing folic acid is widely recommended. This is helping many people fill in this important gap and prevent neural tube defects in both planned and unplanned pregnancies.

Prenatal vitamins containing “natural food folate” might be an option. It just hasn’t been studied enough to know if they prevent neural tube defects. There isn’t enough evidence to replace current, scientifically-sound recommendations.

4. Folic Acid is a More Affordable Option Than Real Food Folate

Prenatal vitamins containing “natural food folate” are much more expensive to make than those containing folic acid. Foods fortified with folic acid and less expensive prenatal vitamins containing folic acid are actively helping to prevent neural tube defects. It’s important to know that you can rely on current recommendations even if you are unable to afford expensive and designer prenatal vitamins. 

5. Folic Acid is a More Stable Form of Folate

Folic acid is used in supplements and for food fortification because is more heat- and light-stable than natural food folate. Basically, this means folic acid won’t be broken down and degraded in the same way during cooking. We also don’t know if the amount of natural food folate still present in prenatal vitamins at the time of consumption matches what is listed on the label. 

Final Thoughts

There are always individuals pushing the envelope of science and bringing new ideas to light. This can inspire additional studies that give us more information. Sometimes the new information leads to updated recommendations. While there is an ongoing debate on folate, it’s important to understand that we are not there yet when it comes to changing current recommendations that we know work for those with and without the MTHFR C677T gene variant.