Mechanistic insights into the health benefits of fish-oil supplementation against fine particulate matter air pollution: a randomized controlled trial

BACKGROUND: Dietary fish-oil supplementation might attenuate the associations between fine particulate matter (PM(2.5)) and subclinical biomarkers. However, the molecular mechanisms remain to be elucidated. This study aimed to explore the molecular mechanisms of fish-oil supplementation against the PM(2.5)-induced health effects. METHODS: We conducted a randomized, double-blinded, and placebo-controlled trial among healthy college students in Shanghai, China, from September 2017 to January 2018. A total of 70 participants from the Fenglin campus of Fudan University were included. We randomly assigned participants to either supplementation of 2.5-gram fish oil (n = 35) or sunflower-seed oil (placebo) (n = 35) per day and conducted four rounds of health measurements in the last two months of the trial. As a post hoc exploratory study, the present untargeted metabolomics analysis used remaining blood samples collected in the previous trial and applied a Metabolome-Wide Association Study framework to compare the effects of PM(2.5) on the metabolic profile between the sunflower-seed oil and fish oil groups. RESULTS: A total of 65 participants completed the trial (34 of the fish oil group and 31 of the sunflower-seed oil group). On average, ambient PM(2.5) concentration on the day of health measurements was 34.9 µg/m(3) in the sunflower-seed oil group and 34.5 µg/m(3) in the fish oil group, respectively. A total of 3833 metabolites were significantly associated with PM(2.5) in the sunflower-seed oil group and 1757 in the fish oil group. Of these, 1752 metabolites showed significant between-group differences. The identified differential metabolites included arachidonic acid derivatives, omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids that were related to unsaturated fatty acid metabolism, which plays a role in the inflammatory responses. CONCLUSION: This trial suggests fish-oil supplementation could mitigate the PM(2.5)-induced inflammatory responses via modulating fatty acid metabolism, providing biological plausibility for the health benefits of fish-oil supplementation against PM(2.5) exposure. TRIAL REGISTRATION: This study is registered at ClinicalTrails.gov (NCT03255187). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12940-022-00908-1.