Association between Combined Metals and PFAS Exposure with Dietary Patterns: A Preliminary Study

The global burden of chronic diseases has been increasing, with evidence suggesting that diet and exposure to environmental pollutants, such as per- and polyfluoroalkyl substances (PFAS) and heavy metals, may contribute to their development. The Dietary Inflammatory Index (DII) assesses the inflammatory potential of an individual's diet. However, the complex interplay between PFAS, heavy metals, and DII remains largely unexplored.

The goal of this cross-sectional study was to investigate the associations between diet operationalized as the DII with individual and combined lead, cadmium, mercury, perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS) exposures using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018.

Descriptive statistics, a correlational analysis, and linear regression were initially used to assess the relationship between the variables of interest. We subsequently employed Bayesian kernel Machine regression (BKMR) to analyze the data to assess the non-linear, non-additive, exposure-response relationships and interactions between PFAS and metals with the DII.

The multi-variable linear regression revealed significant associations between the DII and cadmium and mercury. Our BKMR analysis revealed a complex relationship between PFAS, metal exposures, and the DII. In our univariate exposure-response function plot, cadmium and mercury exhibited a positive and negative linear relationship, respectively, which indicated a positive and negative relationship across the spectrum of exposures with the DII. In addition, the bivariate exposure-response function between two exposures in a mixture revealed that cadmium had a robust positive relationship with the DII for different quantiles of lead, mercury, PFOA, and PFOS, indicating that increasing levels of cadmium are associated with the DII. Mercury's bivariate plot demonstrated a negative relationship across all quantiles for all pollutants. Furthermore, the posterior inclusion probability (PIP) results highlighted the consistent importance of cadmium and mercury with the inflammatory potential of an individual's diet, operationalized as the DII in our study, with both showing a PIP of 1.000. This was followed by PFOS with a PIP of 0.8524, PFOA at 0.5924, and lead, which had the lowest impact among the five environmental pollutants, with a PIP of 0.5596.

Our study suggests that exposures to environmental metals and PFAS, particularly mercury and cadmium, are associated with DII. These findings also provide evidence of the intricate relationships between PFAS, heavy metals, and the DII. The findings underscore the importance of considering the cumulative effects of multi-pollutant exposures. Future research should focus on elucidating the mechanistic pathways and dose-response relationships underlying these associations in a study that examines causality, which will enable a deeper understanding of the dietary risks associated with environmental pollutants.