The effect of omega-3 fatty acids on a biomarker of head trauma in NCAA football athletes: a multi-site, non-randomized study

Jeffery L Heileson, Anthony J Anzalone, Aaron F Carbuhn, Andrew T Askow, Jason D Stone, Stephanie M Turner, Lyn M Hillyer, David W L Ma, Joel A Luedke, Andrew R Jagim, Jonathan M Oliver, Jeffery L Heileson, Anthony J Anzalone, Aaron F Carbuhn, Andrew T Askow, Jason D Stone, Stephanie M Turner, Lyn M Hillyer, David W L Ma, Joel A Luedke, Andrew R Jagim, Jonathan M Oliver

Abstract

Background: American-style football (ASF) athletes are at risk for cardiovascular disease (CVD) and exhibit elevated levels of serum neurofilament light (Nf-L), a biomarker of axonal injury that is associated with repetitive head impact exposure over the course of a season of competition. Supplementation with the w-3 fatty acid (FA) docosahexaenoic acid (DHA) attenuates serum Nf-L elevations and improves aspects of CVD, such as the omega-3 index (O3I). However, the effect of combining the w-3 FA eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) with DHA on, specifically, serum Nf-L in ASF athletes is unknown. Therefore, this study assessed the effect of supplemental w-3 FA (EPA+DPA+DHA) on serum Nf-L, plasma w-3 FAs, the O3I, and surrogate markers of inflammation over the course of a season.

Methods: A multi-site, non-randomized design, utilizing two American football teams was employed. One team (n = 3 1) received supplementation with a highly bioavailablew-3 FA formulation (2000mg DHA, 560mg EPA, 320mg DPA, Mindset®, Struct Nutrition, Missoula, MT) during pre-season and throughout the regular season, while the second team served as the control (n = 35) and did not undergo supplementation. Blood was sampled at specific times throughout pre- and regular season coincident w ith changes in intensity, physical contact, and changes in the incidence and severity of head impacts. Group differences were determined via a mixed-model between-within subjects ANOVA. Effect sizes were calculated using Cohen's dfor all between-group differences. Significance was set a priori at p< .05.

Results: Compared to the control group, ASF athletes in the treatment group experienced large increases in plasma EPA (p < .001, d = 1.71) and DHA (p < .001, d = 2.10) which contributed to increases in the O3I (p < .001, d = 2.16) and the EPA:AA ratio (p = .001, d = 0.83) and a reduction in the w-6: w-3 ratio (p < .001, d = 1.80). w-3 FA supplementation attenuated elevations in Nf-L (p = .024). The control group experienced a significant increase in Nf-L compared to baseline at several measurement time points (T2, T3, and T4 [p range < .001 - .005, drange = 0.59-0.85]).

Conclusions: These findings suggest a cardio- and neuroprotective effect of combined EPA+DPA+DHA w-3 FA supplementation in American-style football athletes.

Trial registration: This trial was registered with the ISRCTN registry ( ISRCTN90306741 ).

Keywords: American Football; Brain; Concussion; Docosahexaenoic Acid; Eicosapentaenoic Acid; Neurofilament Light.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
Study timeline and blood sampling schedule for each team
Fig. 3
Fig. 3
Effect of ω-3 fatty acid (FA) supplementation from baseline (T1) to the end of season (T6) on proportion (A) eicosapentaenoic acid (EPA), B docosahexaenoic acid (DHA), C docosapentaenoic acid (DPA), D arachidonic acid (AA) of total plasma fatty acids; *indicates a significant difference from baseline (p < .05); †indicates a significant difference between groups (p < .01). All data are mean ± SD
Fig. 4
Fig. 4
Individual changes in the Omega-3 Index (O3I) in the treatment (n = 30) and control (n = 35) groups during a NCAA football season. The solid lines indicate the cutoff values for low- and high-risk categories. Values < 4 % are high-risk and values > 8 % are low-risk. Red blood cell O3I was calculated from plasma using a validated equation [48]. *indicates a significant difference compared to baseline (p < .001); †indicates a significant difference between groups (p < .001)
Fig. 5
Fig. 5
Effect of ω-3 fatty acid (FA) supplementation from baseline (T1) to the end of season (T6) on the (A) ω-6:ω-3 ratio, B eicosapentaenoic acid (EPA):arachidonic acid (AA) ratio; *indicates a significant difference from baseline (p < .001); †indicates a significant difference between groups (p < .001). All data are mean ± SD
Fig. 6
Fig. 6
Effect of ω-3 fatty acid (FA) supplementation on serum neurofilament light (Nf-L; % change from baseline) in the control and treatment teams. *indicates a significant difference compared to baseline (p < .05); †indicates a significant difference between groups (p < .05). All data are mean (± SE)
Fig. 7
Fig. 7
Effect of supplemental ω-3 fatty acids on serum neurofilament light (Nf-L; % change from baseline) in control and treatment teams in athletes categorized as starters. *indicates a significant difference compared to baseline (p < .05). All data are mean (± SE)

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