Per- and Poly-fluoroalkyl Substances (PFAS) in Circulation in a Canadian Population: Their Association with Serum Liver Enzyme Biomarkers and Piloting a Novel Method to Reduce Serum PFAS

View ORCID Profile Jennifer J. Schlezinger , View ORCID Profile Anila Bello , View ORCID Profile Kelsey M. Mangano , View ORCID Profile Kushal Biswas , Paridhiben P. Patel , View ORCID Profile Emily H. Pennoyer , View ORCID Profile Thomas M.S. Wolever , View ORCID Profile Wendy J. Heiger-Bernays , View ORCID Profile Dhimiter Bello

doi: https://doi.org/10.1101/2024.08.02.24311171 Jennifer J. Schlezinger 1 Department of Environmental Health, Boston University , Boston, Massachusetts, USA Anila Bello

2 Department of Public Health, Zuckerberg College of Health Sciences, University of Massachusetts , Lowell, Massachusetts, USA

Kelsey M. Mangano

3 Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts , Lowell, Massachusetts, USA

Kushal Biswas

3 Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts , Lowell, Massachusetts, USA

Paridhiben P. Patel

3 Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts , Lowell, Massachusetts, USA

Emily H. Pennoyer 1 Department of Environmental Health, Boston University , Boston, Massachusetts, USA Thomas M.S. Wolever 4 INQUIS Clinical Research, Ltd. (formerly GI Labs) , Toronto, Ontario, Canada Wendy J. Heiger-Bernays 1 Department of Environmental Health, Boston University , Boston, Massachusetts, USA

2 Department of Public Health, Zuckerberg College of Health Sciences, University of Massachusetts , Lowell, Massachusetts, USA

Dhimiter Bello

3 Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts , Lowell, Massachusetts, USA

Abstract

Extensive use of per- and polyfluoroalkyl substances (PFAS) has resulted in their ubiquitous presence in human blood. PFAS exposures have been associated with multiple adverse human health effects including increased risk of liver damage, elevated serum lipids, impaired vaccine response, adverse birth outcomes and cancer. Biomonitoring studies have focused on measuring long-chain PFAS, but these are being replaced by shorter chain PFAS and PFAS with alternative structures, resulting in incomplete understanding of human exposures. Here, we take advantage of serum samples collected as part of a clinical trial testing the efficacy of a dietary fiber intervention to reduce serum cholesterol to investigate exposure to legacy and replacement PFAS chemicals in Canadian participants. Serum samples were collected from 72 participants in 2019-2020 at baseline and after 4 weeks of the intervention and were analyzed for 17 PFAS species. The highest geometric mean concentrations of PFAS measured at baseline corresponded to PFOSA (7.1 ng/ml), PFOS (4.2, ng/ml), PFOA (1.8 ng/ml) and PFHxS (1.3 ng/ml). Short chain PFAS including PFBuA, PFHxS and/or PFHpA were detected in 100% of participants and GenX was detected in 70% of participants. Analyses of associations between PFAS serum concentrations and biomarkers of adverse health outcomes showed the PFBuA, PFHxA, PFDA and PFOSA were associated with higher serum gamma-glutamyl transferase concentrations but not with measures of serum total or low-density lipoprotein cholesterol. Comparison of PFAS concentrations at baseline and after a 4-week follow-up showed that total PFAS concentrations decreased in both the control and cholesterol intervention groups. However, the suite of PFAS of concern identified by the United States National Academies of Sciences, Engineering, and Medicine, significantly decreased only in the cholesterol intervention group. This observation suggests that a dietary fiber intervention may reduce PFAS body burden, but future intervention studies need to control for PFAS exposure sources and extend beyond 4 weeks. Overall, the results show that exposures to short-chain and alternative PFAS are common in this Canadian population.

Competing Interest Statement

TMSW is an employee of INQUIS, Inc.; neither he nor INQUIS own any intellectual property related to the study product or study results and have no financial interest in any food companies with which INQUIS does, has done or may do business

Clinical Trial

Funding Statement

The study was made possible in part by a seed grant from the University of Massachusetts Lowell and support from the National Institutes of Health (R21 ES032882, JJS) and FEMA EMW-2020-FP-00078 (AB, DB).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

As determined by the Boston University Institutional Review Board, secondary analysis of previously collected, deidentified samples described herein does not constitute human subjects research.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Data Availability

All data produced in the present study are available upon reasonable request to the authors.