Last week, many in the nutrition and medical fields let out a collective sigh. That’s because there is good quality nutrition research, from actual humans in randomized control trials, showing the importance of folic acid supplementation during pregnancy. Taking a multivitamin with 400 mcg of folic acid (the form of folate found in most supplements) can prevent birth defects associated with the brain and spinal cord. And organizations like the March of Dimes have done a good job getting the word out about folic acid to women of childbearing age. The FDA even just announced it would allow corn flour to be fortified with folic acid, in order to prevent birth defects among women who eat corn as a staple in their diet.

So when headlines such as “Folic Acid May Increase Autism Risk” splashed across newspapers and television screens, it was a blow to the progress that has been made in this area, and if not addressed quickly, could lead to hundreds if not thousands of babies born with serious, preventable birth defects. “The data does not say that folic acid supplements cause, or even may cause, autism,” says Linus Pauling Institute Principal Investigator Emily Ho, Ph.D.

In fact, says Ho, the available data show the opposite: supplementation was actually associated with a decreased risk of autism. “Women who are pregnant or thinking of becoming pregnant need to make sure they are getting folate and should not stop taking their prenatal folic acid supplements,” says Ho.

Here’s how the whole thing came about: researchers at Johns Hopkins Bloomberg School of Public Health shared some interesting, yet unpublished and non peer-reviewed research at the International Meeting for Autism Research. It was in the form of a conference abstract, which means their peers had not yet had the chance to vet the full data set, the study design, or other factors. This is a vital step in the academic and scientific community; many findings don’t ever make it to publication because they don’t pass muster in the review process. That said, even the limited data presented at the conference showed that women who took a multivitamin 3-5/week had a lower chance of having a child with autism spectrum disorder.

The misleading headlines arose from a secondary finding related not to maternal folic acid supplementation during pregnancy, but to a women’s blood levels at or near the time of delivery. This is a crucial distinction: how much folate a woman gets from food or supplements is a very different notion than how much folate is circulating in a woman’s blood at any given time. The latter refers to how a body, with its unique genetic makeup, processes folate.

These findings do warrant further study, but far from reading them as a signal for women to stop taking the recommended supplement of 400 mcg of folic acid, they suggest that there may be a subset of women who process folate differently. The researchers involved don’t yet understand why these women from the study had such high levels of folate in their blood, which wouldn’t be present from typical folic acid supplementation.

This phenomenon can and should be reviewed and explored in more rigorous detail. Potential harms of excessively high folic acid supplements (>400 mcg) should also be better studied. The thing is, the researchers who presented their work at the conference, seem to agree with these conclusions. Some have blamed the misleading news headlines on the media relations team at Johns Hopkins which issued the press release and stirred up the controversy.

For more on the nitty-gritty, read on.

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A Conversation on Folic Acid With Giana Angelo, Ph.D.

 

Giana Angelo, Ph.D., is a nutrition scientist with the Linus Pauling Institute’s Micronutrient Information Center. In the below interview, she provides context and details about the recent folate findings, in order to clarify the science behind the headlines.

 

What are the takeaways from the conference abstract?

First off, it’s really important to remember that we are talking about a conference abstract. That means we lack important information about the study design and study population; we have not seen the full data set and statistical analysis; and the findings have not yet been externally reviewed by experts the field. It is extremely premature to make any definitive statements about this data.

That said, the take home messages from the conference abstract include the following:

• Maternal multivitamin use (3-5 times/week) was associated with a reduced risk of autism spectrum disorders (ASD) across all trimesters.
• High maternal folate and vitamin B12 concentrations in the blood were associated with an increased risk of ASD. I’m emphasizing in the blood here because it is an important distinction. The abstract linked high blood levels of folate (not the amount of folate eaten in food or taken as supplements) to an increased risk of ASD.
• The association between high maternal folate concentration in the blood (plasma, to be exact) and ASD was observed at very high concentrations of plasma folate (>59 nmol/L); this concentration far exceeds the upper limit of the normal range of plasma folate concentrations (13.5-45.3 nmol/L) according to the World Health Organization (WHO).

Should women capable of becoming pregnant continue taking folic acid supplements?

Yes! The data does not say that folic acid supplements cause autism.

The science is clear that folate deficiency increases the risk of having a baby with a neural tube defect (NTD) and that folic acid supplementation dramatically reduces the risk of NTDs.

What’s the optimal dose?

400 micrograms/day of supplemental folic acid in addition to the folate consumed from a mixed diet.

Do we need further studies in this area?

Yes. This sort of observation helps shed light on relationships that warrant further study. The abstract suggests that there may be a subset of women who metabolize/process folate and vitamin B12 differently, and it’s important to understand what is happening inside their body and their cells.

Additionally, this abstract does not tell us why abnormally high blood folate may be linked with autism spectrum disorders in certain women — there are many factors (which were not examined in this study) that could accompany or lead to high blood folate concentration and now scientists need to identify and explore those possibilities.

What are the potential consequences of headlines about this non peer-reviewed research?

Many of the headlines are misleading and inaccurate. The fear is that pregnant women will stop taking folic acid supplements.

What is the bottom-line for women?

Well said by the Atlantic: “Taking supplemental folate during pregnancy is still firmly, clearly, recommended.”

The current recommendations still stand. Pregnant women and women capable of becoming pregnant should supplement with 400 micrograms/day of folic acid in addition to the folate consumed from a mixed diet.