Why ACOG and CDC Continue to Recommend Folic Acid Over Folate Despite Research Advancements

Steph Greunke

Why ACOG and CDC Continue to Recommend Folic Acid Over Folate Despite Research Advancements

Intro 

We’ve been clear that we believe that Folate (in the form L-methylfolate) is superior to Folic Acid when it comes to perinatal supplementation. We’re also aware that many major organizations, including the American College of Obstetrics and Gynecology (ACOG) and Centers for Disease Control (CDC) continue to recommend Folic Acid. 

This disconnect has sparked a question in many of your minds, and we hear you.  Why do these organizations recommend Folic Acid instead of L-methylfolate? Which is really better? You’re confused and not sure what to believe. So, we want to address this head on. 

The Needed Approach

First, let's clarify our approach. We meticulously craft our supplements based on research, historical usage, and input from perinatal practitioners. Unlike others, we don't compromise on quality or take shortcuts. Our products, like our Methylfolate-containing Prenatal Multi, are carefully developed from scratch, with every ingredient and dosage choice made intentionally.

Given gaps in women's health research, we supplement our findings with insights from practitioners and real-world observations. While use of folic acid was a vital breakthrough, we now recognize L-methylfolate as a superior alternative due to its better utilization by the body.

Excess folic acid intake poses concerns, as it can accumulate in the body. Fortunately, L-methylfolate offers a highly bioavailable solution, supported by evidence showing its effectiveness in boosting maternal folate levels.

A Quick Refresher 

In case you need a quick refresher on the difference between Folate and Folic Acid, here it is: 

Folic Acid: This synthetic form isn't found naturally in foods but is common in supplements and fortified foods like rice and cereal.

Food Folate: Naturally present in foods like leafy greens and legumes, but it can be challenging to get enough, especially for women during pregnancy.

Both Folic Acid and food-based Folate need to undergo a conversion process in the body before they can be utilized. Folic Acid is converted into Methyltetrahydrofolate (MTHF), but about 40-60% of people have a genetic variation that affects this conversion.

Our supplement uses L-methylfolate, the active and readily usable form of folate, ensuring optimal absorption, even for those with genetic variations impacting folate conversion.

What Research Exists Around the Effectiveness of Folate Supplementation?

Since the argument of ACOG and the CDC is that “Folic Acid is the only type of Folate shown to help prevent neural tube defects,” you would be wise to wonder, what research is there around the effectiveness of L-methylfolate in pregnancy? 

While there isn’t as much research around L-methylfolate in pregnancy as there is Folic Acid, due to ethical limitations in recreating early folic acid studies, there is a growing body of compelling and reliable information to substantiate L-methylfolate’s use.

In a Key Opinion Leader interview in Reviews in Obstetrics & Gynecology, James A. Greenberg, MD, from the Department of Obstetrics and Gynecology at Brigham and Women’s Hospital and the Department of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School, discusses the form of Folate in prenatal supplementation with Stacey J. Bell DSc, RD. 

They acknowledge, “it is reasonable to question the safety and efficacy of L-methylfolate, because up until recently, only Folic Acid was available for prenatal vitamins." However, they point to a study in which healthy women were randomly assigned to consume 400 µg of folic acid, 416 µg of L-methylfolate (the bioequivalent dose of folic acid), and 208 µg of l-methylfolate (half dose). 

Each group experienced increases in plasma Folate and decreases in homocysteine concentrations (although unsurprisingly the half dose of l-methylfolate had a significantly smaller increase in plasma folate compared with the other two groups). These findings suggest that L-methylfolate is bioactive and behaves predictably by increasing plasma levels of Folate and decreasing homocysteine.

Their conclusion, based on this and other research, is that due to “the high prevalence of [the MTHFR variant] and the importance of assuring that pregnant women get adequate supplementation, L-methylfolate may be the best option to avoid blood Folate deficiencies.”

Furthermore, the study notes that excessive intake of Folic Acid could mask an undiagnosed Vitamin B12 deficiency, and that it was “unlikely” that L-methylfolate would mask Vitamin B12 deficiency. Therefore, L-methylfolate may be a better option for supplementation.

Another review in the Journal of Perinatal Medicine looked at whether 5-methyltetrahydrofolate could be used as an alternative to folic acid for the prevention of neural tube defects. It reviewed a number of studies but ultimately concluded that “supplementation of the natural form is a better alternative to supplementation of Folic Acid. Supplemental [L-methylfolate] can effectively improve Folate biomarkers in young women in early pregnancy in order to prevent neural tube defects.” It specifically pointed to a study in the American Journal of Clinical Nutrition that concluded that a mean serum Folate level of approximately 50 nmol/L was achieved by supplementing with 400 μg of either 5-MTHF or Folic Acid for 12 weeks.

If I Know I Don’t Have the MTHFR Variant, is Folic Acid Better?

You don’t know for sure whether or not you have the MTHFR variant unless you have had genetic testing. But if you have, and you know that you don’t, you might be wondering if Folic Acid is better in that case. 

The short answer is no. 

Research has shown that excess Folic Acid supplementation can build up and remain unmetabolized in the body.

In fact, a study in the American Journal of Clinical Nutrition evaluated the effect of mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. The study found that unmetabolized folic acid (UMFA) was detectable in more than 90% of maternal and cord plasma samples tested. The study concluded that UMFA concentrations in maternal and fetal circulation warrant additional investigation, since this excess UMFA may affect long-term health outcomes of the baby. While these long-term ramifications are still being studied, we know enough to know that high doses of Folic Acid should be questioned for the sake of future health outcomes.

Another study notes, “It is now clear that the practice of prescribing high doses of synthetic folic acid should be at least a matter for debate. 5-MTHF, the “active” folate that is immediately available for conversion of homocysteine to methionine, should be proposed instead of Folic Acid for periconceptional support and even for nutritional supplementation in general.”

In addition, a retrospective, comparison study looked at supplementation with Folate and Folic Acid in pregnant women alongside Vitamin B12 with respect to hemoglobin levels. The women studied either used a prenatal supplement containing L-methylfolate and a higher level of B12 or one with Folic Acid. Women were followed during pregnancy until term. In contrast with women who used a prenatal product that contained Folic Acid, those who had L-methylfolate and a higher level of B12 in their prenatal supplement had significantly higher hemoglobin levels at the end of the second trimester and at delivery. Based on this study, it appeared that women benefited from L-methylfolate in their prenatal vitamin in terms of having a lower incidence of anemia.

Furthermore, research suggests that it may not be just mother and baby who are affected by high Folic Acid supplementation. One study found alterations of the human sperm epigenome (the “programming” of sperm that affects gene expression, or how genetics play out in baby’s health) associated with high-dose folic acid supplementation, effects that were exacerbated by a common polymorphism in MTHFR.

If L-methylfolate Is Superior, Why Do Major Medical Organizations Recommend Folic Acid?

So the big question: if plenty of evidence exists to suggest that L-methylfolate is superior to Folic Acid, why is Folic Acid still recommended? In short, it seems there’s only one explanation:

Official recommendations lag scientific research. This lag is significant, often 15 years or more.

Think about it. We’ve had evidence for years that trans fats were bad for us. But it wasn’t until 2015 that the FDA got on board. And even then, food manufacturers weren’t required to change their practices until 2018. Choline has been studied for its importance in pregnancy and with respect to overall human health since at least the 1980s, but it wasn’t until 1998 that there was an official RDA, and it is still missing from the vast majority of supplements (despite over 95% of the population being deficient).

It takes a lot for an official recommendation to change, and rightfully so, these organizations don’t take recommendation updates lightly. So while the evidence is building, it’s not yet enough for major medical organizations to spend the time and money to change a decades-long recommendation.

There are simply more studies on Folic Acid. This is because when supplementation was introduced in 1998, synthetic Folic Acid was the only option. It was inexpensive and accessible, and so it was studied. Still to this day, synthetic Folic Acid remains a cheaper and more accessible option. And if it is the ONLY option for a pregnant woman to take, then yes, she is better off taking it than allowing herself to be deficient during pregnancy.

The Bottom Line

There's a growing body of research highlighting the benefits of supplementing with the active form of Folate over Folic Acid. L-methylfolate, unlike Folic Acid, is already active within the body, eliminating the need for conversion or activation. It's the primary type of folate found in our blood, including serum, red blood cells, and even cord blood, which is the fetal blood supply.

Moreover, L-methylfolate doesn't mask Vitamin B12 deficiency, a critical consideration during pregnancy. Unlike Folic Acid, it doesn't lead to the buildup of unmetabolized Folic Acid in the body, potentially averting negative downstream effects. Studies also indicate that individuals with the MTHFR variant, a genetic variation affecting folate metabolism, respond better to methylfolate than Folic Acid.

Research supports the effectiveness of L-methylfolate in preventing neural tube defects, with no evidence suggesting it's less effective than Folic Acid. Additionally, L-methylfolate carries a low risk of toxicity, unlike Folic Acid, even with higher intake. Despite potential delays in official guidance, we recommend L-methylfolate over Folic Acid based on current research findings.

Our commitment extends to continuous monitoring of the latest nutrition research and clinical experience. We remain open to learning and adapting our approach to ensure optimal perinatal nourishment as new information emerges. 

 

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Steph Greunke, MS, RD, CPT, PMH-C

Stephanie Greunke is a registered dietitian that specializes in prenatal/postnatal nutrition, behavioral psychology, and holds additional certifications in perinatal mental health and fitness. She's a key contributor and advisor to Needed as well as Needed’s Head of Practitioner Relationships. Steph is the owner of Postpartum Reset, an online postpartum nutrition course, and the co-host of "Doctor Mom" podcast.

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