Interventions to Reduce Serum Per- and Poly-Fluoroalkyl Substances Levels, Improve Cardiovascular Risk Profiles, and Improve Epigenetic Age Acceleration in US Firefighters: Protocol for Randomized Controlled Trial

Background: Occupational cancer and acute cardiac events are the leading causes of death among firefighters. Increased exposure to toxicants on the fire ground, such as polycyclic aromatic hydrocarbons, benzene, and per- and poly-fluoroalkyl substances (PFAS), has been linked to certain cancers, cardiovascular disease, accelerated epigenetic aging, and other adverse health effects. PFAS are a major concern because they are persistent, can bioaccumulate, and are present in several firefighting tools. Compared to the general population, firefighters have elevated serum levels of some types of PFAS. A randomized clinical trial in Australian firefighters found that routine blood and plasma donation for 1 year led to decreased serum PFAS levels, although health outcomes were not directly measured in that study. Objective: In collaboration with fire service leadership in Arizona, the Firefighter Collaborative Research Project (FCRP) was established to evaluate the effectiveness of 3 interventions in a randomized controlled trial design to reduce serum PFAS levels, reduce cancer and cardiovascular risk, and improve overall health and wellness in US firefighters. Methods: This study aimed to recruit and enroll up to 1500 active firefighters between August 2023 and October 2024. Between August 2023 and October 2024, active firefighters were recruited and randomized into a study arm based on their eligibility, including serum PFOS levels, for the specific arms. The trial arms include (1) blood and plasma donation, (2) zone 2 physical activity, and (3) intermittent fasting. FCRP outcomes include serum PFAS reduction (arm 1), epigenetic age acceleration (all arms), cardiovascular conditioning (arm 2) and cognitive outcomes (all arms), mental health (all arms), and overall disease risk (all arms). Each study arm includes an intervention and a control group. At enrollment and end of the study, participants provide blood and urine samples and complete a comprehensive questionnaire on their occupational and health history, exposures, and lifestyle behaviors. At the end of the study, participants also participated in a cognitive evaluation. Depending on the study arm, participants may additionally complete a cardiopulmonary exercise test at baseline and follow-up, a mid-study survey, and a mid-study blood and urine collection. Results: Participant activities and data collection will conclude by December 2025. Conclusions: The FCRP is a randomized controlled trial that aims to test the effectiveness of fire service–selected interventions in reducing serum PFAS levels. Study results will contribute to potential interventions that could be used to reduce serum PFAS levels in firefighters.