| Project Detail |
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 has raised public concern due to the possible adverse health effects of PFAS. 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 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. 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. PFAS exposure has been associated with increased serum cholesterol and liver enzymes, which pose a major impact to 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. 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 using a novel statistical approach (target trial emulation) to establish causal effects in observational data. In WP4 the mechanisms by which PFAS affect lipid metabolism in human liver cells will be investigated (overview see figure 2). The project will break new grounds 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, which will guide authorities in the handling and advise of hot-spots and regulation of PFAS to reduce future CVD. |
