Nutritional Optimization for Brain Health in Contact Sports: A Systematic Review and Meta-Analysis on Long-Chain ω-3 Fatty Acids and Neurofilament Light

Summary: Background: Accumulating evidence has highlighted the acute and chronic impact of repetitive subconcussive head impacts (rSHIs) in contact sports. Neurofilament-light (Nf-L), a brain-derived biomarker of neuroaxonal injury, elevates in concert with rSHI. Recently, long-chain ω-3 polyunsaturated fatty acids (LC ω-3 PUFAs) supplementation has been suggested to mitigate brain injury from rSHI as reflected by attenuation of Nf-L concentrations within contact sport athletes. Objective: Using a systematic review with a meta-analysis, we aimed to determine the effect of LC ω-3 PUFA supplementation on Nf-L concentrations in athletes routinely exposed to rSHI. Methods: Electronic databases (PubMed and CINAHL) were searched from inception through January 2024. One-stage meta-analysis of individual participant-level data was used to detect changes in Nf-L concentrations between LC ω-3 PUFA and control/placebo (PL) groups from baseline to midseason (MS) and postseason (PS). Least square means (±SE) for Nf-L change from baseline were compared by treatment group for MS/PS using contrast t tests. Significance was set a priori at adjusted P ≤ 0.05. Results: Of 460 records identified, 3 studies in collegiate American football players (n = 179; LC ω-3 PUFA = 105, PL = 71) were included in the meta-analysis. Compared with PL, the change in Nf-L concentrations was statistically similar at MS [mean difference (MD) = –1.66 ± 0.82 pg·mL–1, adjusted P = 0.09] and significantly lower at PS (MD = –2.23 ± 0.83 pg·mL–1, adjusted P = 0.02) in athletes following LC ω-3 PUFA supplementation. Conclusions: Our findings demonstrate preliminary support for the prophylactic administration of LC ω-3 PUFA in contact sport athletes exposed to rSHI; however, further research is required to determine the effective dosage required.This trial was registered at OSF (DOI: https://doi.org/10.17605/OSF.IO/EY5QW).