The Effects of Fish Oil Supplementation on the Brain Health of Collegiate Football Athletes

Study of Effect of Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) Supplementation on Biomarkers of Sub-Concussion Injuries in American Football

Determine if the daily docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) supplement will reduce serum levels of biomarkers of sub-concussion injuries over a course of American football season among collegiate football athletes.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury (TBI); Chronic Traumatic Encephalopathy (CTE)
• Intervention / Treatment: Dietary supplement: Fish Oil (DPA+EPA 2:1 ratio) Capsules; Dietary supplement: High Oleic Safflower Oil Capsules

Detailed Description

American football is one of the most popular sports in the U.S. Yet this sport is associated with increased risk of concussion (also known as mild traumatic brain injury, or mTBI) and sub-concussive injury from repeated head impacts (RHI) due to the aggressive and high-speed nature of the game. Current protective equipment used by players are not sufficient to reduce concussion incidence and severity, nor are there any therapeutics available to prevent concussion. This study is a randomized, double-blind, placebo controlled trial to determine if an omega-3 polyunsaturated fatty acid (PUFA) fish oil supplement containing 3.0 grams of docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) can reduce blood biomarkers of sub-concussion injuries compared to placebo (high-oleic safflower oil) over a course of the American football season among collegiate football athletes.

The dosage of DHA/EPA used in this study is generally safe, and procedures involved, monthly blood draws, surveys, and Magnetic Resonance Imaging (MRI), pose minimal risks to participants. While this study provides no direct benefit to participants, successful outcomes of this study can benefit the society by shedding light on development of potential preventative therapeutics for sports-induced mTBI and brain injury from RHI. The risk-benefit profile is appropriate for conducting this study. Based on preclinical studies and previous clinical study results, the investigators expect that in comparison to placebo treatment, DHA and EPA treatment throughout the course of one American football season can maintain lower levels of sub-concussion associated biomarkers, inflammatory cytokines, and cardiovascular risk markers. The investigators also expect participants treated with DHA and EPA to have lower brain MRI imaging markers of sub concussion injury.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • University of Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 23 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1) University of Arizona National Collegiate Athletic Association (NCAA) Division I American football athletes cleared to participate in university athletics as determined by the team physician.

Exclusion Criteria:

1. Chronic daily anti-inflammatory drugs (>20 d).
2. Medications for blood lipids.
3. Active fish oil or omega-3 fatty acid supplementation.
4. Consumption of more than two servings of fish per week.
5. Injured and unable to participate in regularly schedule conditioning or competitions.
6. Acute concussion experienced within 30 days of starting the study.
7. Fish allergies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fish Oil Capsules; Participants in the treatment arm will receive 3 grams of DHA and EPA (2:1 weight ratio) 3 times a week for 25-weeks during regular football season.	Dietary supplement: Fish Oil (DPA+EPA 2:1 ratio) Capsules; The Treatment Arm intervention consists of providing participants with 3 grams of DHA and EPA (2:1 weight ratio) in capsular form. In order to meet the required 3 grams of DHA and EPA, participants were given 6 capsules to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 3 times a week during the regular football season.
Placebo Comparator: Safflower Oil Capsules; Participants in the treatment arm will receive 3 grams of high-oleic safflower oil) in a 1:1 allocation ratio for 25-weeks during regular football season.	Dietary supplement: High Oleic Safflower Oil Capsules; The Placebo Arm intervention consists of providing participants with 3 grams of high-oleic safflower oil in a 1:1 allocation ratio in capsular form. In order to maintain the "study masking", participants in the Placebo Arm were given 6 capsules (the same as the Treatment Arm) to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 3 times a week during the regular football season.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in brain biomarkers due to sub-concussion injury - Nf-L	This primary outcome covers the change in the plasma brain biomarker Neurofilament Light Chains (Nf-L) due to sub-concussion injury from baseline to predetermined measurement time points. Nf-L (neuron specific intermediate proteins) are released upon injury to neurons and axons. Measured in picograms per milliliter (pg/ml)	Baseline; then once a month until the end of the study, up to 8 months.
Changes in brain biomarkers due to sub-concussion injury - Tau	This primary outcome covers the change in the plasma brain biomarker Tau protein due to sub-concussion injury from baseline to predetermined measurement time points. Tau protein accumulates in the brain after injury. Tau protein is measured in picograms per milliliter (pg/ml)	Baseline; then once a month until the end of the study, up to 8 months.
Changes in brain biomarkers due to sub-concussion injury - UCH-L1	This primary outcome covers the change in the plasma brain biomarker Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) due to sub-concussion injury from baseline to predetermined measurement time points. UCH-L1 levels are elevated in the cerebrospinal fluid (CSF) and serum for several days after severe traumatic brain injury. UCH-L1 is measured in nanograms per milliliter (ng/ml)	Baseline; then once a month until the end of the study, up to 8 months.
Changes in sub-concussion injury related inflammation biomarkers - CRP	This primary outcome covers the change in the plasma inflammation biomarker C-reactive Protein (CRP), a marker of general inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. CRP is measured in milligrams per liter (mg/L)/	Baseline; then once a month until the end of the study, up to 8 months.
Changes in sub-concussion injury related inflammation biomarkers - TNF-α	This primary outcome covers the change in the plasma inflammation biomarker Tumor Necrosis Factor-alpha (TNF-α), a cytokine and mediator of inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. TNF-α is measured in picograms per milliliter (pg/ml).	Baseline; then once a month until the end of the study, up to 8 months.
Changes in sub-concussion injury related inflammation biomarkers - IL-6	This primary outcome covers the change in the plasma inflammation biomarker Interleukin-6 (IL-6), a cytokine and mediator of inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. IL-6 is measured in picograms per milliliter (pg/ml)	Baseline; then once a month until the end of the study, up to 8 months.

Collaborators and Investigators

• Sponsor: University of Arizona
• Investigators: Principal Investigator: Floyd Chilton, Ph.D., University of Arizona; Principal Investigator: Roberta Brinton, Ph.D., University of Arizona

Publications and helpful links

General Publications

• Raikes AC, Hernandez GD, Mullins VA, Wang Y, Lopez C, Killgore WDS, Chilton FH, Brinton RD. Effects of docosahexaenoic acid and eicosapentaoic acid supplementation on white matter integrity after repetitive sub-concussive head impacts during American football: Exploratory neuroimaging findings from a pilot RCT. Front Neurol. 2022 Sep 15;13:891531. doi: 10.3389/fneur.2022.891531. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Actual): January 28, 2020
• Study Completion (Actual): January 28, 2020

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: MRI; Biomarker; Concussion; Football; CTE (Chronic Traumatic Encephalopathy); mTBI (Mild Traumatic Brain Injury); Nf-L (Neurofilament Light Chain)
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neurodegenerative Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injury, Chronic; Brain Injuries; Brain Injuries, Traumatic; Brain Diseases; Chronic Traumatic Encephalopathy
• Other Study ID Numbers: IRB1904553365

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No