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

Project description

Reducing health risks of PFAS chemicals

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a group of man-made chemicals widely used in products such as non-stick cookware and food packaging. PFAS, known for their environmental persistence and resistance to degradation, have been detected in the environment, resulting in widespread human and wildlife exposure. Funded by the European Research Council, the PFAS foreverywhere project aims to determine if PFAS exposure causally increases serum cholesterol and liver enzymes. The project will expand on the findings that cholestyramine significantly reduces serum PFAS levels, offering a potential approach for their elimination. Results will provide important insight into the causal relationships between PFAS exposure and lipid metabolism, paving the way towards the mitigation of PFAS-related cardiovascular disease risks.

Objective

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.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-ADG

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Host institution

SYDDANSK UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 500 000,00
Address
CAMPUSVEJ 55
5230 Odense M
Denmark

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Region
Danmark Syddanmark Fyn
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 500 000,00

Beneficiaries (1)

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