Head Injury Treatment With Healthy and Advanced Dietary Supplements: A Pilot Randomized Controlled Trial of the Tolerability, Safety, and Efficacy of Branched Chain Amino Acids in the Treatment of Concussion in Adolescents and Young Adults

Concussion is a common injury in the adolescent and young adult populations. While branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild to moderate traumatic brain injury (TBI), to date, no studies have been performed evaluating the efficacy of BCAAs in concussed adolescents and young adults. The goal of this pilot trial was to determine the efficacy, tolerability, and safety of varied doses of oral branched chain amino acid (BCAA) supplementation in a group of concussed adolescents and young adults. The study was conducted as a pilot, double-blind, randomized controlled trial of participants ages 11-34 presenting with concussion to outpatient clinics (sports medicine and primary care), urgent care, and emergency departments of a tertiary care pediatric children's hospital and an urban tertiary care adult hospital, between 6/24/2014 and 12/5/2020. Participants were randomized to one of five study arms (placebo and 15g, 30g, 45g, and 54g BCAA treatment daily) and followed for 21 days after enrollment. Outcome measures included daily computerized neurocognitive tests (processing speed, the a priori primary outcome; and attention, visual learning, and working memory), symptom score, physical and cognitive activity, sleep/wake alterations, treatment compliance, and adverse events. In total, 42 participants were randomized, 38 of whom provided analyzable data. We found no difference in our primary outcome of processing speed between the arms, however, there was a significant reduction in total symptom score (decrease of 4.4 points on a 0-54 scale for every 500 g of study drug consumed, p-value for trend = 0.0036, uncorrected) and return to physical activity (increase of 0.503 points on a 0-5 scale for every 500 g of study drug consumed, p-value for trend = 0.005 uncorrected). There were no serious adverse events. Eight of 38 participants reporting a mild (not interfering with daily activity) or moderate (limitation with daily activity) adverse event; there were no differences in adverse events by arm, with only 2 reported mild adverse events (both gastrointestinal) in the highest (45g and 54g) BCAA arms. Though limited by slow enrollment, small sample size, and missing data, this study provides the first demonstration of efficacy, as well as safety and tolerability of BCAAs in concussed adolescents and young adults-- specifically, a dose response effect in reducing concussion symptoms and a return to baseline physical activity, in those treated with higher total doses of BCAAs. These findings provide important preliminary data to inform a larger trial of BCAA therapy to expedite concussion recovery.