Genetics play a significant role in autism, but exposure to environmental contaminants such as air pollution and pesticides likely contributes, too. An NIEHS workshop held June 21-22 explored whether some nutrients may protect people from the harms of environmental exposures that may relate to the likelihood of developing autism or associated traits.

Over two days, researchers from more than a dozen institutions across the country presented information related to the potential synergistic effects of certain foods and nutrients. They discussed what we know about the effects of nutritional interventions such as folate on autism spectrum disorder, and what we can learn from research into other health outcomes, like the effects of consuming fish contaminated by methylmercury.

“While we normally think about risk reduction from chemical exposures in terms of removing or decreasing exposures, sometimes that can be difficult to achieve,” said Cindy Lawler, Ph.D., chief of the NIEHS Genes, Environment, and Health Branch. “An alternative is to focus on increasing beneficial nutritional exposures, such as folate or polyunsaturated fatty acids (PUFAs), with the premise that these can mitigate risk from harmful exposures.”

Effects of pollution and diet

Environmental exposures experienced before and during critical windows of pregnancy may have lasting health effects, like autism spectrum disorder.

At Emory, Gaskins focuses on the connection between environment, diet, and fertility in both men and women. (Photo courtesy of Audrey Gaskins)

Traffic pollution can decrease reproductive potential in both men and women, couples that live near highways have a higher likelihood of infertility, said Audrey Gaskins, Sc.D., an epidemiologist at Emory University’s Rollins School of Public Health. She looked at data from the Environment and Reproductive Health Study, focusing on couples from the Massachusetts General Hospital Fertility Center between 2004 and 2019. The dataset includes information on participants’ lifestyle, diet, medical and reproductive history, as well as residential addresses, which researchers linked to air pollution models through six fertilization cycles.

Gaskins hypothesized that air pollution could damage reproduction through a variety of biological mechanisms, including oxidative stress, endocrine disruption, DNA methylation, an altered immune response, and inflammation. The more air pollution, the greater the decrease in participants’ reproductive success. Folic acid, a synthetic form of folate, however, seemed to counteract those effects. The more folic acid a pregnant woman took, the higher the probability of a live birth.

“Obviously, much more research is needed,” said Gaskins, whose work was funded by a grant from NIEHS. “There are very few preconception cohorts that measure both diet and environmental exposures.”

Benefits of folic acid

The benefits of folic acid extend beyond reproduction. Often taken by pregnant women in the form of a multivitamin to reduce the risk of spina bifida, the supplement may reduce the risk of autism as well.

“We don’t have interventions that are good preventative strategies for these neurodevelopmental disorders” like autism and schizophrenia, said Joshua Roffman, M.D., director of the Early Brain Development Initiative at Massachusetts General Hospital. Yet folic acid is safe, widely available, and could be leveraged to reduce risk.

Research published in 2019 by Rebecca Schmidt, Ph.D., a molecular epidemiologist at the University of California, Davis showed a reduced associated risk of autism in younger siblings when their mothers took a prenatal vitamin with folic acid during pregnancy. Among 241 children whose older siblings had autism spectrum disorder, 32% developed autism when their mothers did not take a prenatal vitamin during the first month of pregnancy, compared to 14% when their mothers did take a vitamin supplement. Enriched breads and cereals now contain folic acid, but increasing the number and type of foods fortified with the vitamin could further decrease risk.

Other components of a prenatal vitamin or supplements like vitamin D or polyunsaturated fatty acids may also have neurodevelopmental benefits. “We need additional studies on potential mechanisms that these exposures share, and that could help us figure out how to advance strategies for any mitigation of risk,” said Schmidt.

It’s complicated

Although a growing body of research points to the potential protective effects of nutrition on autism spectrum disorder, only a handful of nutrients have been examined exploring the connection. Presenters cautioned that efforts to investigate nutritional interventions should also consider dose, timing, equity, and access to treatment.

“I think this is an exciting area of research, but we should be very thoughtful about the idea that nutritional interventions are not as easy as we think,” said Youssef Oulhote, Ph.D., an environmental epidemiologist at the University of Massachusetts Amherst, who co-organized the meeting with Kristen Lyall, Sc.D., an epidemiologist at Drexel University.

“The workshop was a great way to think more deeply about the methods we should be using and the questions we should be asking,” noted Lyall.

(Susan Cosier is a contract writer for the NIEHS Office of Communications and Public Liaison.)