Scientists from the Keck School of Medicine at the University of California found that exposure to a mixture of synthetic chemicals found widely in the environment alters several critical biological processes, including the metabolism of fats and amino acids, in both children and young adults.
This process disruption is connected to an increased risk of a broad range of diseases, including developmental disorders, cardiovascular disease, metabolic disease, and many types of cancer.
Known as per- and polyfluoroalkyl substances, or PFAS, these man-made chemicals are used in a wide range of consumer and industrial products. PFAS are sometimes called “forever chemicals” because they break down very slowly and accumulate in the environment and human tissue.
Although individual PFAS are known to increase the risk of several types of disease, this study “Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study”, published in Environmental Health Perspectives, reportedly is the first to evaluate which biological processes are altered by exposure to a combination of multiple PFAS, which is important because most people carry a mixture of the chemicals in their blood.
“However, the metabolic pathways linking PFAS exposure and human disease are unclear. We examined associations of PFAS mixtures with alterations in metabolic pathways in independent cohorts of adolescents and young adults,” wrote the investigators.
“Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children’s Health Study (CHS) were included in the analysis. Plasma PFAS and the metabolome were determined using liquid chromatography/high-resolution mass spectrometry.
“A metabolome-wide association study was performed on log-transformed metabolites using Bayesian regression with a g-prior specification and g-computation for modeling exposure mixtures to estimate the impact of exposure to a mixture of six ubiquitous PFAS (PFOS, PFHxS, PFHpS, PFOA, PFNA, and PFDA). Pathway enrichment analysis was performed using Mummichog and Gene Set Enrichment Analysis. Significance across cohorts was determined using weighted Z-tests.
“In the SOLAR and CHS cohorts, PFAS exposure was associated with alterations in tyrosine metabolism (metanalysis p=0.00002) and de novo fatty acid biosynthesis (p=0.03), among others. For example, when increasing all PFAS in the mixture from low (∼30th percentile) to high (∼70th percentile), thyroxine (T4), a thyroid hormone related to tyrosine metabolism, increased by 0.72 standard deviations (SDs; equivalent to a standardized mean difference) in the SOLAR cohort (95% Bayesian credible interval (BCI): 0.00, 1.20) and 1.60 SD in the CHS cohort (95% BCI: 0.39, 2.80).
“Similarly, when going from low to high PFAS exposure, arachidonic acid increased by 0.81 SD in the SOLAR cohort (95% BCI: 0.37, 1.30) and 0.67 SD in the CHS cohort (95% BCI: 0.00, 1.50). In general, no individual PFAS appeared to drive the observed associations.”
“Our findings were surprising and have broad implications for policymakers trying to mitigate risk,” said Jesse A. Goodrich, PhD, assistant professor of population and public health sciences and lead author of the study. “We found that exposure to a combination of PFAS not only disrupted lipid and amino acid metabolism but also altered thyroid hormone function.”
One finding that stood out, according to Goodrich, was the fact that PFAS exposure had an effect on thyroid hormone function, which has a critical role in growth and metabolism. Because of this, changes in thyroid hormones play an important role in child development during puberty, which can have important effects on a range of diseases later in life, including diabetes, cardiovascular disease, and cancer.
Important public health consideration
Another important finding was the fact that exposure to a mixture of PFAS, rather than a single chemical of this type, drove the disruption of these biological processes. This finding was consistent across the two cohorts, even though they had different levels of PFAS exposure.
Almost all people in the United States have detectable levels of several PFAS, which are in a wide variety of products including waterproof clothing and food packaging, in their blood. An estimated 200 million people in the United States have drinking water with PFAS levels that are considerably higher than the levels recommended by the U.S. Environmental Protection Agency in 2022.
Some manufacturers have phased out the use of individual PFAS, but the authors of this study concluded that this research shows why it may be more important to regulate PFAS as a class of chemicals.
“We are really only beginning to understand the range of effects that these chemicals have on human health,” said Leda Chatzi, MD, PhD, professor of population and public health sciences and another of the study’s authors. “While current interventions have focused on phasing out the use of individual PFAS, such as PFOS and PFOA, this research shows why the focus should be on reducing exposure to all PFAS chemicals.”
