PFAS exposure; relationship to serum lipids in children and adults, mechanism of action and potential treatment of high exposed individuals

Introduction

Perfluoroalkyl substances (PFAS) are widely used, persist in the environment, and are present in all human populations. Many hot-spot areas across Europe, in which humans are exposed through contaminated water or food, have raised public concern due to the possible adverse health effects of PFAS.

Project Aim

The overarching aim of my proposal is to determine if PFAS exposure is causally linked to increased serum cholesterol and liver enzymes, and if PFAS elimination can be enhanced.

Pilot Findings

Pilot findings from our first-ever randomized cross-over trial suggest that administration of the bile acid sequestrant cholestyramine significantly reduces serum PFAS in 34 high-exposed individuals, probably by reducing intestinal reabsorption.

Work Package 1 (WP1)

In work package 1 (WP1), I will explore the promising pilot findings in a rigorously conducted randomized cross-over trial. A trial administering the food supplement psyllium, which also reduces bile reabsorption, will be undertaken.

Health Implications

PFAS exposure has been associated with increased serum cholesterol and liver enzymes, which pose a major impact on human health due to the causal link to cardiovascular diseases (CVD). It remains unclear whether the associations are causal, and mechanisms by which PFAS affect lipid metabolism are not established.

Work Packages 2-3 (WP2-3)

In WP2-3, I will study the causal relationships between child and adult PFAS exposure and serum lipids and liver enzymes in high-quality prospective cohorts. This will be done using a novel statistical approach (target trial emulation) to establish causal effects in observational data.

Work Package 4 (WP4)

In WP4, the mechanisms by which PFAS affect lipid metabolism in human liver cells will be investigated (overview see figure 2).

Conclusion

The project will break new ground for our understanding of the mechanism of action of PFAS on lipid metabolism and the relation with serum cholesterol and liver enzymes, as well as whether PFAS elimination can be enhanced. This will guide authorities in the handling and advising of hot-spots and regulation of PFAS to reduce future CVD.