by Dr. Olivia Janz (Registered Acupuncture & Chinese Medicine Practitioner)
If you’re planning to conceive, you’ve probably come across advice about taking folate. It’s essential for early pregnancy, helping to prevent neural tube defects (NTDs) and supporting healthy fetal development. But what’s often overlooked is that not all folate is created equal. Many prenatal vitamins, including one of the most widely recommended products, contain synthetic folic acid instead of the natural and more bioavailable form, 5-MTHF (5-Methyltetrahydrofolate). Understanding the difference between these two forms is crucial for your health and your baby’s well-being.
The Difference Between Folic Acid and Folate
Folate is a naturally occurring B vitamin (B9) found in foods like leafy greens, legumes, and liver. It plays a key role in DNA synthesis, cell growth, and repair—all of which are vital during pregnancy. Folic acid, on the other hand, is the synthetic version found in most prenatal vitamins and fortified foods. While folic acid has been credited with reducing NTD risk, it requires conversion in the body before it can be used—and that’s where things can get complicated for some people.
The MTHFR Gene Mutation and Folate Metabolism
Up to 40% of the population carries a mutation in the MTHFR (methylenetetrahydrofolate reductase) gene, which reduces their ability to convert folic acid into its active form, 5-MTHF. This means that for many women, a significant portion of folic acid remains unmetabolized in the bloodstream rather than converting into folate to be used for essential processes. A study in 2014 found that 86% of folic acid in the hepatic portal vein remained unmetabolized, while natural folate taken in the form 5-MTHF was efficiently processed.
The presence of unmetabolized folic acid (UMFA) in the bloodstream raises concerns about potential negative effects, including immune dysfunction, masking of vitamin B12 deficiency, and possible impacts on fetal development. Even more concerning, UMFA has been detected in umbilical cord blood, raising concerns about how it may affect newborns.
There is a genetic test available to determine whether you carry the MTHFR gene mutation that affects folic acid metabolism. However, this test is not bulk billed and requires an out-of-pocket fee (approx. $385). If you prefer to skip genetic testing, taking 5-MTHF directly ensures absorption, regardless of whether you have the mutation or not.
The Risks of Elevated Homocysteine and Pregnancy Complications
Beyond neural tube defects, folate is essential for regulating homocysteine (Hcy) levels. Elevated homocysteine has been linked to serious pregnancy complications, including:
- Recurrent pregnancy loss
- Preeclampsia
- Preterm delivery
- Placental abruption
- Fetal growth restriction
- Gestational diabetes
Research also indicates that high levels of homocysteine may be bad for the baby’s growth & development.
Folate and Autism Risk Reduction
Emerging research has also observed anomalies in folate and homocysteine metabolism in children with autism spectrum disorder (ASD). Some studies suggest that folate supplementation during pregnancy may lower the risk of ASD and even improve children’s language competency. This adds another compelling reason to opt for bioavailable 5-MTHF over synthetic folic acid.
Why was folic acid introduced?
Although folate is present in whole foods, obtaining enough for a healthy pregnancy through diet alone is difficult. Natural folate is highly sensitive to heat and easily destroyed during cooking, significantly reducing its availability. Additionally, the sheer amount of food required to meet optimal folate levels would be impractical for most people.
To address this, folic acid was introduced as a more heat-stable alternative that could be added to fortified foods, making it easier for the general population to meet folate requirements & leading to a significant decline in neural tube defects (NTDs) for those not affected by the MTHFR gene mutation. However, individuals WITH the MTHFR mutation are unable to benefit from this with their struggle to convert folic acid into its active form, causing unmetabolized folic acid to accumulate in the bloodstream.
Because of this, supplementing with a bioavailable form such as 5-MTHF is often recommended to ensure adequate intake and proper absorption. This is especially important for those with the MTHFR mutation, but even individuals without the mutation can benefit from taking 5-MTHF, as it bypasses the need for conversion and is readily used by the body.
The Best Choice for Pregnancy: 5-MTHF & How to supplement properly
Research shows that while folic acid and 5-MTHF can both raise blood folate levels in general, 5-MTHF raises blood folate levels much faster. Nevertheless, guidelines still recommend the use of folic acid in pregnancy planning as the research on neural tube defects was conducted with folic acid, not 5-MTHF. Guidelines have also not yet acknowledged the benefits of 5-MTHF in the very population who would seem to benefit most, and do not acknowledge the potential negative impacts of unmetabolized folic acid.
Guidelines support folate supplementation for at least three months before conception and to continue throughout the first trimester to prevent NTDs. However, because pregnancy increases your folate needs by up to tenfold, supplementation should continue throughout the entire pregnancy.
When choosing a prenatal vitamin, take a close look at the ingredient list and ensure it contains 5-MTHF (5-Methyltetrahydrofolate) rather than only the synthetic folic acid. This simple switch can make a significant difference in how well your body absorbs and utilizes this crucial nutrient. This may very well be the missing piece of the puzzle for women unable to fall pregnant despite following the current health guidelines, those with unexplained primary infertility, or for women who have experienced one or more miscarriages.
If you’re unsure where to find a quality supplement, consider seeking guidance from a natural health practitioner or booking an appointment with me. Together, we can ensure that you’re taking the best possible supplements to support a healthy pregnancy and a thriving baby.
Selected References
Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial. Caffrey, McNulty et al. 2021 https://pubmed.ncbi.nlm.nih.gov/33750355/
Miraglia N, Dehay E. Folate Supplementation in Fertility and Pregnancy: The Advantages of (6S)5-Methyltetrahydrofolate. Altern Ther Health Med. 2022 May;28(4):12-17. PMID: 35653630.
Lian Z, Wu Z, Gu R, Wang Y, Wu C, Cheng Z, He M, Wang Y, Cheng Y, Gu HF. Evaluation of Cardiovascular Toxicity of Folic Acid and 6S-5-Methyltetrahydrofolate-Calcium in Early Embryonic Development. Cells. 2022 Dec 7;11(24):3946. doi: 10.3390/cells11243946. PMID: 36552710; PMCID: PMC9777352. https://pmc.ncbi.nlm.nih.gov/articles/PMC9777352/
Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? Obeid, Holzgreve, Pietrzik et al. 2013 https://pubmed.ncbi.nlm.nih.gov/23482308/
Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health. Carboni 2022 https://pmc.ncbi.nlm.nih.gov/articles/PMC9380836/
Folic acid handling by the human gut: implications for food fortification and supplementation. Patanwala, King et al. 2014 https://pmc.ncbi.nlm.nih.gov/articles/PMC4095662/
A Novel Review of Homocysteine and Pregnancy Complications. Dai, Fei et al. 2021 https://pmc.ncbi.nlm.nih.gov/articles/PMC8121575/
Evidence of unmetabolised folic acid in cord blood of newborn and serum of 4-day-old infants. Sweeney, McPartlin et al. 2005 https://pubmed.ncbi.nlm.nih.gov/16277775/
Maternal biomarkers for early prediction of the neural tube defects pregnancies. Yadav, Kumar, Rai 2020 https://pubmed.ncbi.nlm.nih.gov/33188559/
Association of pre-eclampsia risk with maternal levels of folate, homocysteine and vitamin B12 in Colombia: A case-control study. Serrano, Quintero-Lesmes et al. 2018 https://pubmed.ncbi.nlm.nih.gov/30521542/
Blood folic acid, vitamin B12, and homocysteine levels in pregnant women with fetal growth restriction. Jiang, Kao, Chen 2016 https://pubmed.ncbi.nlm.nih.gov/28002587/
Hyperhomocysteinemia among Omani autistic children: a case-control study., Ali, Waly et al. 2011, https://pubmed.ncbi.nlm.nih.gov/22187679/
Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence. DeVilbiss, Gardner et al. 2015 https://pubmed.ncbi.nlm.nih.gov/26243379/
Folic acid supplements in pregnancy and severe language delay in children. Roth, Schjolberg et al. 2011 https://pubmed.ncbi.nlm.nih.gov/21990300/
Supplementation with Folic Acid or 5-Methyltetrahydrofolate and Prevention of Neural Tube Defects: An Evidence-Based Narrative Review. Nutrients. 2024 Sep 18;16(18):3154. doi: 10.3390/nu16183154 https://pmc.ncbi.nlm.nih.gov/articles/PMC11435031/
MTHFR Gene Variant and Folic Acid Facts. https://www.cdc.gov/folic-acid/data-research/mthfr/index.html