American football athletes are exposed to sub-concussive impacts over the course of the season resulting in elevations in serum neurofilament light (NFL), a biomarker of axonal injury. Docosahexaenoic acid (DHA) has been reported to reduce axonal trauma associated with traumatic brain injury in rodent models. However, the optimal dose in American football athletes is unknown. This study examined the effect of differing doses of DHA on serum NFL over the course of a season of American football.

In a randomized, double-blind, placebo-controlled, parallel design eighty-one (n = 81) National Collegiate Athletic Association (NCAA) Division I American football athletes were assigned to ingest either 2 g•d, 4 g•d, 6 g•d of DHA, or placebo. Blood was sampled at specific times over the course 189 days coincident with changes in intensity, hours of contact, and likely changes in head impacts. Standardized magnitude-based inference was used to define outcomes.

DHA supplementation increased plasma DHA in dose-dependent manner (mean difference from baseline; ± 90% CL; 2 g•d: 1.3; ±0.6; 4 g•d: 1.6; ±0.7%; 6 g•d: 2.8; ±1.2%). Serum NFL increased to a greater extent in starters (AUC, 1995 ± 1383 pg•mL•day) versus non-starters (1398 ± 581 pg•mL•day; p = 0.024). Irrespective of dose, supplemental DHA likely attenuated serum NFL coincident with increases in serum NFL by likely small and moderate magnitude (ES = 0.4 to 0.7).

Findings from this study, the first large scale study examining potential prophylactic use of DHA in American football athletes, include identification of optimal dose of DHA suggest a neuroprotective effect of DHA supplementation.