Impact of Fish Oil Supplementation on Plasma Levels of Fatty Acid-Containing Lipid Classes, Lipid Molecular Species, and Biomarkers of Brain Injury in Contact Sport Athletes

Abstract

Contact sports involve a high risk of concussive injury and a higher risk of injury from repeated subconcussive head impacts (RSHI) that do not meet the threshold for a concussion diagnosis. RSHI increase an athlete's risk of biochemical and structural brain damage that can lead to cognitive and behavioral deficits later in life. Omega-3 highly unsaturated fatty acids, docosahexaenoic acids (DHA) and eicosapentaenoic acids (EPA), found in fish oil supplements and fatty fish, produce biologically active molecules that resolve inflammation and therefore their use in brain injury recovery has garnered substantial interest within the field of sports medicine research. The work reported in this dissertation was undertaken in response to the urgent need to better understand the risks of RSHI and the potential for omega-3 highly unsaturated fatty acids to mitigate the trauma. We conducted a double-blind randomized control trial to investigate the impact of DHA+EPA supplementation on biomarkers related to neurotrauma and inflammation in American football participants. We used lipidomics to analyze changes in plasma lipid classes and molecular species following DHA+EPA supplementation. Additionally, we performed a neuroimaging study to evaluate changes in gray and white matter integrity throughout the American football season, comparing those with and without fish oil supplementation. To further understand the role RSHI play in structural and functional changes in the brain and the relationship between blood-based and neuroimaging biomarkers of brain injury, we conducted a pilot study involving mixed martial arts athletes. In this pilot study we examined the correlation between kinematic data from mouth guard sensors and neuroimaging data with blood-based biomarkers of brain injury before and after both contact and non-contact training sessions. Our research with collegiate American football athletes showed a notable increase in plasma concentrations of both DHA and EPA, specifically in molecular forms capable of crossing the blood-brain barrier following fish oil supplementation. Throughout the regular football season, we observed a significant rise in serum levels of neurofilament light, a biomarker indicating axonal injury. Neuroimaging results unveiled structural changes in the brain after a season of American football, affecting both white and gray matter pathways. Notably, fish oil supplementation did not alleviate the negative effects of RSHI, as reflected in neurofilament light plasma concentrations. However, participants with the highest plasma concentrations of DHA+EPA tended to exhibit lower neurofilament light concentrations. In our pilot study with mixed marital arts athletes, we established connections between immediate changes in brain hemodynamics (blood flow and brain strain), plasma neurofilament light concentrations, and head kinematics (number of impacts, impact angular acceleration, impact angular velocity), along with oxygenated hemoglobin concentrations after RSHI. Overall, our work underscores the importance of ongoing research combining neuroimaging and blood-based biomarkers in understanding and addressing brain injury risks in contact sports and the potential for fish oil supplementation to mitigate the trauma from RSHI.