Docosahexaenoic Acid (Dha) for the Treatment of Pediatric Sport-Related Concussion: Results of a Feasibility Trial

Abstract

Introduction: The rate of sport-related concussion (SRC) has increased steadily over the past two decades in the pediatric population. Docosahexaenoic acid (DHA), an Omega-3 fatty acid important for brain development in children, may aid in recovery following SRC. The purpose of this study was to determine the feasibility, outcomes, and safety of DHA as early treatment for SRC in pediatrics. Methods: A double-blind, randomized, placebo-controlled feasibility trial was conducted. Inclusion criteria were ages 14-18 and SRC within 4 days of enrollment. Exclusion criteria included taking DHA, radiographic evidence of TBI, participation in motorized sports, or previous concussion within past 6 months. Following diagnosis of concussion and initiation of standard treatment, subjects were randomized in a 1:1 fashion to DHA or a placebo and were instructed to take 2 capsules twice daily for 12 weeks. DHA capsules contained a total of 2000 mg of DHA/day and PLACEBO capsules contained corn and soy oil. Both were flavored with masking agents. Subjects were followed prospectively. Standard clinical assessments, SCAT-3 symptoms, ImPACT scores, BESS scores, adverse effects, and drug compliance was collected at enrollment, 1-week, 2-weeks, 4-weeks and 12-weeks. Demographics, day of injury symptoms, injury characteristics, and sport played were also collected. Subjects who demonstrated normal neurocognitive testing, complete symptom resolution and were cleared to begin a return to play (RTP) progression prior to the 4-week follow-up visit were permitted to forgo additional study visits, but requested to return for the 12-week visit. Groups were compared using Mann-Whitney tests for continuous variables and chi-square tests for categorical variables. Results: 40 subjects were enrolled; 20 in the DHA group (mean age: 16.02 years; 65% male) and 20 in the PLACEBO group (mean age: 15.97 years; 70% male). No significant differences in demographics, sport, symptoms, ImPACT scores, or BESS scores at enrollment were noted between groups. 25 (62.5%) subjects completed the 12-week visit. Overall drug compliance was 61.57% in the DHA group compared to 66.34% in the PLACEBO group (p=0.727). Subjects in the DHA group were symptom-free 4 days earlier than the PLACEBO group (16.1 vs. 20.9 days, p=0.082), demonstrated normal ImPACT neurocognitive testing (12.2 vs. 16.8 days, p=0.382), and were cleared to begin a RTP progression (21.4 vs. 23.4 days, p=0.115) sooner than those in the PLACEBO group. Two adverse effects were noted in the DHA group. One event was determined to be unrelated to the study. The second event was drug-related eructation and considered minor. No adverse effects were reported in the PLACEBO group. Conclusion: This study demonstrated that use of high-dose DHA for treatment of SRC in pediatrics is feasible and safe. DHA may allow for a faster symptom-free state and for an earlier return to play, but a large-scale trial is needed.

Nutritional interventions to support acute mTBI recovery

“…In addition, specific nutritional supplements and infusions administered during the acute period post mTBI onset may have a role in facilitating patients' recovery. In the present review intakes of nutrients and non-nutrients, including omega-3s fatty acids DHA and EPA (55,58,61), vitamin D (62), magnesium oxide (56), NAC (5), HSL (59), and nootropic cerebrolysin (60) demonstrated a positive effect on recovery outcomes for patients post mTBI. However, due to the diversity between interventions and the limited number of studies conducted in humans, a meta-analysis was not possible.…”

“…Included studies reported a diverse range of recovery measures and outcomes for patients during acute recovery periods 0-14 days for adults and 0-28 days for children post mTBI onset (8,66). Nine out of the 11 included studies reported positive recovery outcomes utilizing nutritional interventions in those that sustained an mTBI (5, 55,56,[58][59][60][61][62].…”

“…Eleven studies investigated nutritional interventions employed post-concussion/mTBI onset during the acute and subacute phases in humans, aiming to improve recovery outcomes (Table 2). Studies were published from Malaysia (57), the United States (55,56,58,61,63,64), Indonesia (59), China (60), Iraq (5) and Asia (62), between 2009 and 2020. There were…”

“…Three human RCTs investigated omega-3 fatty acids, specifically DHA, to determine its role in acute recovery following a sports related mTBI/concussion in pediatric (55) and adult populations (58,61) when administered within 24-120 h post-injury onset. Miller et al (55) trialed a daily dose of 2,000 mg DHA over 12 weeks (n = 40); for symptom resolution, sooner commencement, and RTP outcomes following sportrelated concussion (SRC). DHA led to positive outcomes for return to sport (RTS) initiation (14 vs. 19.5 days) and RTP initiation (21.4 vs. 23.4 days) for patients compared to placebo.…”

“…Long chain omega-3 fatty acids DHA and/or EPA, supplemented within 24-120 h post mTBI were shown to facilitate symptom resolution and sooner RTP outcomes in three human trials (55,58,61). DHA and EPA are fatty acids obtained through the diet via certain fish and algae-based products and supplements (20,29,67); and benefit patients in supporting performance, recovery, and reducing illness and injury risks (68,69).…”