Folic Acid: Friend or Foe? Excess Folic Acid During Pregnancy Without Enough Choline Can Promote Obesity in Offspring

By Jessica Ulbikas

13 May 2022

Consuming too much or too little of certain prenatal vitamins and nutrients may pose long-term health consequences for offspring, according to a new study from the Department of Human Health and Nutritional Sciences.

Most expectant mothers know that folic acid is critical during pregnancy to support healthy neurological development in the fetus.  But consuming excess folic acid, which commonly occurs with prenatal vitamins, can predispose offspring towards obesity.   

Now, new findings show that consuming excess folic acid without also consuming enough choline, an essential nutrient similar to B vitamins, may contribute to risk of metabolic diseases by altering the gut microbiota.

“It's quite exciting that the gut microbiota can be modulated by various environmental factors, including diet,” says Dr. Clara Cho, who led the study. “Changes to the diet can influence your disease risk, but it can also influence the way you respond to nutrients.”

There is not much known about the complex relationships between nutrient consumption in mothers, and how their offspring’s health outcomes are influenced by their gut microbiota. This is exactly what Cho and her team are trying to discover.

Previous research by Cho and others found a connection between pregnant rats consuming high levels (relevant to human consumption) of multivitamins and obesity in male and female offspring, but only male obesity could be explained by the high levels of folic acid.  In this study, Cho and her team wanted to determine what role, if any, the nutrient choline might also play in this process.

“The metabolic pathways of folic acid and choline are intricately linked, and it has also been suggested that both nutrients may be important modifiers of the gut microbiota,” explains Cho.

The team fed pregnant rats diets that were supplemented with different levels of folic acid and choline. Male and female rat offspring were then observed for traits associated with obesity.  

When rats consumed a diet high in folic acid but without choline, offspring developed obesity and characteristics of the metabolic syndrome:  they had higher body weight, increased food intake, higher body fat percentage, altered physical activity and impaired glucose response compared to the control diet. Notably, both males and females exhibited these obese traits. In contrast, a diet with excess folic acid with choline produced obese traits only in male offspring. 

This exciting result reveals the importance of dietary choline in potentially modulating the effects of excess folic acid. “We talk about folate all the time, but we are actually under consuming choline. Only about 10 percent of the population meets the recommendation for choline,” says Cho.

Choline is readily found in foods such as eggs and meats, as well as select plant foods. However, not everyone can easily obtain the recommended amounts of dietary choline, especially those who may consume a vegan diet.

So how does the gut microbiota factor into this?  The study is the first to show that different maternal diets lead to differences in the composition and function of gut microbiota of offspring, and that these differences varied according to offspring’s sex. 

“The gut microbiota was different across the gestational diet and sex of the offspring,” says Cho. “This really suggests that gut microbiota changes may be impacting the overall metabolic health of these offspring.”

While more research is needed, studies like Cho’s are making important advances in our understanding of how folic acid and choline fit into the big picture of pregnancy, the gut microbiota, and chronic disease risk.  Such research will play a critical role in informing healthcare practitioners, industry leaders, policymakers, and even consumers of prenatal vitamins and nutrients.

Read the full study in the journal Nutrients.

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