High Dose Omega-3 Fatty Acids in the Treatment of Sport Related Concussions

Overview

Concussions are defined as a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces. Currently the standard of care in the treatment for concussions is cognitive and physical rest until symptoms resolve with a graduated return to activity. High dose omega-3 fatty acids have shown to have anti-inflammatory, anti-oxidant, and membrane stabilizing properties. They have also been used in treatment of severe traumatic brain injury. The purpose of this study is to determine if early high dose omega-3 fatty acid supplementation in Division I National Collegiate Athletic Association (NCAA) athletes that have sustained a concussion will decrease the number of days out of competitive sports with a quicker symptom resolution, return to baseline neurocognitive functioning and postural stability using a randomized double blind placebo controlled study design. Once an athlete is identified as having sustained a concussion by the East Carolina University Sports Medicine staff and qualifies for the study, he/she will randomly be assigned to either high dose omega-3 fatty acid or placebo. Both groups will undergo standard and usual care for concussed athletes at East Carolina University. The number of days it takes the athlete to return to competitive athletics will be recorded, along with time to symptom resolution, normalization of their computerized neurocognitive testing (ImPact) and computerized postural stability testing (Biodex BioSway).

In the United States, an estimated 1.7 million people sustain a traumatic brain injury (TBI) annually; associated with 1.365 million emergency room visits and 275,000 hospitalizations annually with associated direct and indirect cost estimated to have been 4 billion in the United States in 2000. Furthermore, the US Center for Disease Control and Prevention estimates that 1.6 to 3.8 million concussions occur in sports and recreational activities annually.3 However, these figures grossly underestimate the total burden of traumatic brain injuries (TBIs) and concussions, because many individuals suffering from mild to moderate TBIs do not seek medical attention. Even though concussion is a type of TBI that has been frequently used interchangeably with mild TBI in the medical literature; mild refers to the initial impact rather than the long-term sequelae from the injury. Historically, the definition of concussion has not been well defined, until the 3rd International Conference on Concussion in Sport (Zurich 2008) defined concussion as a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces. Several common features that incorporate clinical, pathological and biomechanical injury constructs that may be utilized in defining the nature of concussive head injury include: Concussion may be caused either by a direct blow to the head, face, neck or elsewhere on the body with an "impulsive" force transmitted to the head. This injury typically results in the rapid onset of short-lived impairment of neurologic function that resolves spontaneously. It may result in neuropathological changes, but the acute clinical symptoms largely reflect a functional disturbance rather than a structural injury. It results in a graded set of clinical signs and symptoms that may or may not involve loss of consciousness. Resolution of the clinical and cognitive symptoms typically follows a sequential course; however, it is important to note that, in a small percentage of cases, post-concussive symptoms may be prolonged. No abnormality on standard structural neuro-imaging studies is seen in concussion. Current data shows that on average 91% of athletes who sustain a concussion have their symptoms and cognitive impairment resolved in 7 ± 1.5 days and balance deficits resolved by day 5.13 Currently the main treatment for concussion is cognitive and physical rest until symptoms resolve with a graduated return to activity. The neuropathological changes after a concussion result in functional disturbances and the clinical syndrome results from the depolarization and potassium efflux from neurons that trigger the release of excitatory amino-acids like glutamine, which in turn activate N-methyl-D-aspartate (NMDA) receptors and form a pore through which calcium enters the neuron. A large influx of calcium into the cell triggers the lysis of arachidonic acid, calpain activation and initiation of apoptosis, and the formation of reactive oxygen species (ROS). Studies have shown that the incorporation of omega-3 fatty acids into the cell membrane has been associated with decreased generation of intracellular ROS and consequent diminished activation of redox-sensitive transcription factors, such as the nuclear factor- κβ system, modifying the expression of pro-inflammatory genes. Incorporation of omega-3 fatty acids also appears to alter the properties of lipid rafts and caveolae, contributing to membrane fluidity, hormone-receptor binding and the function of membrane associated proteins are affected. Omega-3 fatty acids are also associated with decreased levels of markers and mediators of inflammation such as the cytokines interleukin-1β and tumor necrosis factor (TNF-α). Mills et al looked at the effects of omega-3 fatty acid supplementation in a head injury model in rats. Docosahexaenoic acid (DHA) was started approximately 24 hours after injury, in the following doses: 10 mg/kg/day for group 1 and 40 mg/kg/day for group 2. The number of beta-amyloid precursor protein (APP)-positive axons was used to measure the level of injury. There was a significant quantitative difference of 182 ± 44.6 APP-positive axons in un-supplemented animals versus sham-injured animals (control animals), which had 4.1 ± 1.3 APP-positive axons per square millimeter. Group 1 showed 26.1 ± 5.3 and group 2 showed 19.6 ± 4.7, APP-positive axons. It is notable that the omega-3 fatty acid supplementation groups had a significantly reduced number of APP-positive axons at 30 days after injury to levels similar to those in uninjured animals. This study shows pathologic improvement with high dose omega-3 fatty acid supplementation, specifically DHA, in a head injury rat model. However, there are no current human studies in the medical literature that look at omega-3 fatty acid supplementation in the treatment of concussions. Does high dose omega-3 fatty acid supplementation in Division I NCAA athletes that have sustained a concussion improve time to symptom resolution, neurocognition and postural stability and thus decrease the number of days out of competitive sports? Protocol: Once an athlete qualifies for the study he/she will be randomly be assigned to either high dose omega-3 fatty acid/DHA supplementation or placebo. Demographics of the athlete will be obtained which include: age, gender, sport, academic year, height, weight, BMI, history of prior concussion, migraines, learning disability, or psychiatric diagnosis. Both groups will undergo standard and usual care for concussed athletes at East Carolina University. The physician and the athletic training staff evaluating and clearing the athlete to return to activity will be blinded. Currently East Carolina University employs a regimented return-to-play protocol for every student-athlete that has sustained a concussion. As part of their pre-participation physical, all student-athletes will have a baseline computerized postural stability test using Biodex BioSway and a computerized neurocognitive test using ImPact. At the time of injury a Sport Concussion Assessment Tool 2 (SCAT2) is administered by a certified athletic trainer, and the student-athlete is withdrawn from participation if they are symptomatic and/or have deficits noted. The same day a concussion is suspected a repeat Biodex postural stability test will also be administered and the student-athlete is given a detailed information sheet on instructions for monitoring and follow-up. A repeat Impact neurocognitive test will then be administered within 24 hours after the injury. The student-athlete is then seen and examined by a sports medicine physician to review the results, perform a clinical exam and confirm the diagnosis. The student-athlete is then evaluated daily with a modified Symptom Evaluation Questionnaire found on the SCAT2 by an athletic trainer. When the student-athlete is asymptomatic with activities of daily living (ADLs) for 24 hours, he/she then begins a non-contact return to play protocol resembling Zurich's beginning with a supervised cardiovascular challenge. This includes 30 minutes of supervised light aerobic activity on a treadmill or stationary bike. If the athlete is asymptomatic with the cardiovascular challenge then he/she can progress to noncontact sport specific drills the subsequent day. If the athlete is still doing well he/she can progress their non-contact training drills and start light resistance training the following day. If the student-athlete remains asymptomatic through the non-contact activity progression, he/she then re-takes the computerized neurocognitive test, postural stability assessment and is re-evaluated by the physician. If the postural stability assessment and neurocognitive test are back to baseline the athlete is then cleared at the discretion of the treating sports medicine physician to return to full unrestricted activity. However, if a student-athlete's symptoms continue by day 7 both Impact and Biodex BioSway evaluation will be re-administered. This will be repeated again at 14 days and 30 days post-injury if the student-athlete continues to be symptomatic.