Experts warn PFAS endocrine-disrupting chemicals may drive obesity, osteoporosis

WASHINGTON — A class of endocrine-disrupting chemicals known as PFAS may work as an “environmental trigger” to drive multiple adverse endocrine health effects, including obesity, thyroid dysfunction and low bone mineral density, although researchers caution that more studies on potential associations are needed.

At a congressional briefing Wednesday sponsored by the NIH’s National Institute of Environmental Health Sciences and the Endocrine Society, a panel of experts outlined how human exposure to perfluoroalkyl and polyfluoroalkyl substances — endocrine-disrupting chemicals better known as PFAS — may be associated with a range of adverse outcomes and called on Congress to support efforts for increased research and collaboration between agencies.

“Early studies have shown a link between greater PFAS exposure and increased risk for endocrine outcomes like obesity, but more research is needed specifically to examine factors like exposure timing,” Abby Fleisch, MD, MPH, attending physician in pediatric endocrinology and diabetes at the Center for Outcomes Research and Evaluation at Maine Medical Center, told Endocrine Today.

Defining PFAS

PFAS are a large and expanding group of manmade compounds that are widely used to make everyday products more resistant to stains, grease and water, according to the NIH. The class of more than 4,700 chemicals are used in everything from nonstick cookware to stain-resistant carpeting and firefighting foam. The chemicals remain in the environment for an unknown length of time and take many years to leave the body, according to Mark F. Miller, MS, MBA, PhD, chief of staff of the National Institute of Environmental Health Sciences and commander of the U.S. Public Health Service, said during the briefing.

“Of those 4,700 or more PFAS chemicals, we are only able to measure a very small number — less than two dozen — in water or sediment or biological samples,” Miller said. “As there was a big move from the historical PFAS chemicals that have been used, there has been a great surge in other chemicals that we are finding in samples. We just don’t have a good way to measure them. What we would like to know is are we seeing 90%, or are we seeing 10% with our current analytical capabilities? That will be a next step and a really large hurdle.”

Associations with obesity, osteoporosis

Studies of adults, children and pregnant women suggest that PFAS chemicals play a role in obesity and osteoporosis, Fleisch said during the briefing, and it is “critical” to conduct more research to learn more.

“As a pediatric endocrinologist, I treat increasing numbers of young, obese patients, and I am well aware that diet, physical activity and genetics don’t fully explain why a person becomes obese,” Fleisch said. “Identifying remediable environmental triggers and determining when during the lifespan to intervene is a public health priority.”

Animal models suggest mice exposed to PFAS in early life became obese in later life, Fleisch said. In humans, PFAS exposure is associated with lower testosterone and increased inflammation, both of which predispose a person to obesity, Fleisch said.

Population-based studies, too, suggest an association between PFAS and adverse outcomes. In a post hoc analysis of participants in the Diabetes Prevention Program study, Fleisch and colleagues found that adults with higher PFAS levels at baseline had greater weight gain, greater risk for diabetes and greater risk for elevated total cholesterol during long-term follow-up.

In a surprising finding, the researchers also observed that attention to diet and exercise may attenuate adverse risks from PFAS exposure in the DPP cohort, Fleisch said after the briefing.

“Studies that I’ve been involved in have shown that PFAS were associated with health outcomes in the placebo group, but not in the lifestyle intervention group,” Fleisch said in an interview. “Additional research is needed to understand why and whether that can be replicated in other cohorts.”

In an analysis of the Project Viva cohort, which assessed prenatal exposures and offspring health, Fleisch and colleagues found that women with higher PFAS levels in early pregnancy had greater weight gain during pregnancy. At 3 years postpartum, women with higher PFAS levels in early pregnancy were more likely to develop diabetes. However, among children in Project Viva, the researchers found the PFAS levels measured at a median age of 8 years were not associated with obesity or diabetes risks.

“This raises an important question: When during the lifespan do PFAS have their strongest effects?” Fleisch said. “This will take more research to get to the bottom of this.”

“Mouse and human models also suggest that PFAS exposure in early life is associated with low BMD in late life,” Fleisch said.

“In human autopsy studies, PFAS have been shown to embed in human bone,” Fleisch said. “What is fascinating is PFAS may impair bone health through the same mechanisms through which they may cause obesity.”

Fleisch said she recently received NIH grant funding to assess children in the Project Viva cohort and examine the role of PFAS exposure in mid-childhood on the development of obesity and low BMD as the children progress through adolescence.

“What is really exciting is we have some first findings, showing that children with higher PFAS exposure have lower BMD in mid-childhood,” Fleisch said. “This finding is important, because it suggests that environmental chemicals like PFAS may impact bone health, and it is important because it shows that future studies are necessary to look at the role of PFAS exposure on BMD during adolescence when bone formation is at its peak and being set for life.”

Careful research needed

Some state agencies are reviewing current PFAS research findings from NIH grantees to assess and evaluate the impact of these chemicals on human health, Miller said. In the meantime, Miller noted, it is important for researchers and policy makers to ensure that any PFAS substitutes are safer than the chemicals they replace.

“Many times we have looked at products that we deemed to be unsafe and then were replaced with something we just knew less about,” Miller said. “We want to make sure we don’t get ourselves into an alternative substitution situation where we are replacing with something that could potentially have a greater impact.” – by Regina Schaffer

Disclosures: Fleisch and Miller report no relevant financial disclosures.