Omega-3 Fatty Acids for Brain Injury

Overseen By Kei Kawata

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Must not be taking: Omega-3 supplements

Disqualifiers: Head injury, Cardiovascular diseases, Pregnancy, others

Compensation: Varies

Number of Visits: 24

Duration: 7 weeks

208 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are consuming omega-3 supplements or oily fish, you would need to stop before participating.

What data supports the effectiveness of the treatment Omega-3 Fatty Acids for brain injury?

Research in animals shows that omega-3 fatty acids, especially DHA, can reduce inflammation and improve recovery after brain injury. These studies suggest that omega-3s might help the brain heal better after injury by providing essential nutrients and reducing harmful inflammation. ^{1 2 3 4 5}

Is omega-3 fatty acid supplementation safe for humans?

Omega-3 fatty acids, including DHA and EPA, are generally considered safe and well-tolerated in humans, with evidence suggesting they can be part of mainstream medicine due to their safety profile. ^{2 3 5 6 7}

How does the treatment Omega-3 Fatty Acids differ from other treatments for brain injury?

Omega-3 Fatty Acids are unique because they are a dietary supplement that can help improve brain recovery after injury by reducing inflammation and protecting brain cells. Unlike other treatments, they work by maintaining the integrity of brain cell membranes and supporting nerve function, which can lead to better outcomes after a brain injury. ^{2 5 8 9 10}

What is the purpose of this trial?

The purpose of the proposed double-blind, randomized placebo-controlled trial is to understand how supplementation with fish oil \[docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)\] promote brain health against soccer heading. The study involves taking DHA+EPA or placebo, questionnaires, blood draws, brain imaging, tests to evaluate heart function, and soccer headings.

Eligibility Criteria

This trial is for individuals who regularly play soccer and are interested in the potential brain health benefits of Omega-3 fatty acids. Participants should be willing to undergo questionnaires, blood draws, brain imaging, heart function tests, and perform soccer headings.

Inclusion Criteria

Current or former soccer player

Willing to commit to avoid any sport activity that purposefully uses one's head to maneuver during the study period (American football, ice-hockey, rugby, wrestling, and soccer heading)

At least 5 years of soccer heading experience

Exclusion Criteria

I have not had a head or neck injury in the last 6 months.

Implanted metal/magnetic devices (e.g., orthodontic braces)

I have been diagnosed with a heart or blood pressure condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DHA+EPA or placebo supplementation and undergo soccer heading sessions

7 weeks

Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Omega-3 Fatty Acids

Trial Overview The study is testing whether taking supplements with Omega-3 fatty acids (DHA+EPA) can protect against brain impacts from heading a soccer ball. It's a double-blind study, meaning neither participants nor researchers know who gets the real supplement or placebo.

Participant Groups

Group I: Omega-3 Fatty Acids (EPA plus DHA) Active Control 2 Interventions

DHA+EPA capsules contain purified deep-sea fish oil, made from 100% wild-caught sardines and anchovies with a 3-year shelf life. The capsule shell is made from bovine limed bone with a size of 20 oblongs. Each soft gel capsule contains 480 mg of DHA, 205 mg of EPA, 145 mg of other omega-3 FA, and 10 mg of vitamin E. Participants in the DHA+EPA group will ingest 5 capsules daily \[a total of 3.4 g/d: DHA (2.4 g), EPA (1.0 g)\].

Group II: Placebo: Organic soybean oil pills Placebo Group 2 Interventions

We will use organic soybean oil pills ) as a placebo condition for the DHA+EPA group. One capsule contains 485 mg of organic soybean oil, including negligible amounts of DHA (1.1 mg), EPA (1.7 mg), and vitamin E (10 mg). Participants will ingest 5 capsules daily. Soybean oil is one of the most widely used vegetable oils in the world. Soybean oil contains polyunsaturated fats and 18-carbon omega-3 FA (total omega-3 FA of 73.9 mg per capsule), but very low levels of DHA and EPA, which makes it an excellent placebo counterpart when evaluating the effects of DHA/EPA. The placebo capsule's shelf life, composition, shape, size as the DHA+EPA active comparator.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Omega-3 fatty acids (n-3FA) may provide a nutritional foundation that supports brain healing after severe traumatic brain injury (TBI), as suggested by recent animal research and clinical experience.

Administering n-3FA early in the treatment process, potentially in the emergency department, could improve outcomes for TBI patients, addressing the secondary injury phase characterized by neuroinflammation and other harmful processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic use of omega-3 fatty acids in severe head trauma. Lewis, M., Ghassemi, P., Hibbeln, J.[2021]

In a study using a rat model of pediatric traumatic brain injury (TBI), it was found that a diet supplemented with Docosahexaenoic Acid (DHA) prevented the decrease in brain DHA levels typically seen after injury, suggesting a protective effect against TBI-related deficits.

The research indicated that while DHA supplementation increased DHA levels in the blood, it did not significantly raise brain DHA content after injury, highlighting the complexity of DHA's role in brain health following TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of controlled cortical impact and docosahexaenoic acid on rat pup fatty acid profiles. Schober, ME., Requena, DF., Maschek, JA., et al.[2023]

Mice with adequate dietary α-linolenic acid (ALA) showed a 35% higher brain DHA level, leading to reduced neuroinflammation and improved recovery after traumatic brain injury (TBI) compared to those with marginal ALA intake.

The study suggests that increasing dietary n-3 polyunsaturated fatty acids (PUFAs) like DHA could enhance functional outcomes in humans after TBI, as evidenced by lower pro-inflammatory cytokine levels and better motor function recovery in the mice with higher DHA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced acute neuroinflammation and improved functional recovery after traumatic brain injury by α-linolenic acid supplementation in mice. Desai, A., Park, T., Barnes, J., et al.[2019]

In a rat model of pediatric traumatic brain injury, docosahexaenoic acid (DHA) was found to reduce proinflammatory markers in the hippocampus shortly after injury, suggesting it may help mitigate inflammation early on.

Despite DHA's benefits in reducing inflammation, the overall increase in neuroinflammation markers persisted after injury, indicating that while DHA may improve outcomes, it does not completely alter the inflammatory response following traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docosahexaenoic acid decreased inflammatory gene expression, but not 18-kDa translocator protein binding, in rat pup brain after controlled cortical impact. Schober, ME., Requena, DF., Ohde, JW., et al.[2023]

Supplementation with omega-3 fatty acids (EPA and DHA) significantly increases serum levels of these fatty acids in a dose-dependent manner, which was tested in a study involving 40 rats with traumatic brain injury.

The study found that omega-3 fatty acid supplementation reduced axonal injury markers, such as β-amyloid precursor protein (APP) and caspase-3, to levels comparable to uninjured animals, suggesting a protective effect against traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model. Mills, JD., Bailes, JE., Sedney, CL., et al.[2011]

Acute administration of omega-3 polyunsaturated fatty acids (PUFAs) after traumatic brain injury (TBI) and spinal cord injury (SCI) has shown promise in improving neurological outcomes, highlighting their potential for neuroprotection and neuroregeneration.

The beneficial effects of omega-3 PUFAs are linked to mechanisms such as reduced neuroinflammation, decreased oxidative stress, and enhanced cell survival pathways, suggesting they could be a valuable treatment option for injuries that lead to significant disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids and traumatic neurological injury: from neuroprotection to neuroplasticity? Michael-Titus, AT., Priestley, JV.[2022]

Omega-3 fatty acids (n-3FA) show promise as a treatment for traumatic brain injury (TBI) due to their potential to address neuroprotection, neuroinflammation, and neuroregeneration, supported by strong preclinical evidence and clinical experience.

n-3FA have demonstrated excellent safety and tolerability, suggesting they could be integrated into standard treatment protocols for TBI, especially if administered early and in optimal doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concussions, Traumatic Brain Injury, and the Innovative Use of Omega-3s. Lewis, MD.[2017]

Dietary supplementation with omega-3 fatty acids can help reduce oxidative stress and promote neuronal survival after traumatic brain injury (TBI), as shown in laboratory experiments.

Omega-3 fatty acids may normalize levels of brain-derived neurotrophic factor (BDNF), which is crucial for improving synaptic transmission and protecting brain cells from damage following TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 Fatty acids could alleviate the risks of traumatic brain injury - a mini review. Kumar, PR., Essa, MM., Al-Adawi, S., et al.[2021]

Depleting docosahexaenoic acid (DHA) in the brain significantly worsens recovery from traumatic brain injury (TBI) in mice, as shown by slower recovery in motor function and increased anxiety-like behavior after injury.

Mice with DHA deficiency exhibited greater neuronal death and higher levels of injury markers, indicating that adequate DHA levels are crucial for better outcomes following TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury. Desai, A., Kevala, K., Kim, HY.[2021]

Mice fed an omega-3 fatty acid-enriched diet for 2 months showed reduced behavioral deficits and protected against hippocampal neuronal loss after controlled cortical impact, indicating the efficacy of omega-3s in mitigating brain injury effects.

Omega-3 fatty acids preserved myelin integrity and nerve fiber conductivity, while also reducing inflammation and protecting oligodendrocytes from damage, suggesting their multifaceted role in preventing neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 polyunsaturated fatty acid supplementation improves neurologic recovery and attenuates white matter injury after experimental traumatic brain injury. Pu, H., Guo, Y., Zhang, W., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Therapeutic use of omega-3 fatty acids in severe head trauma. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of controlled cortical impact and docosahexaenoic acid on rat pup fatty acid profiles. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Reduced acute neuroinflammation and improved functional recovery after traumatic brain injury by α-linolenic acid supplementation in mice. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Docosahexaenoic acid decreased inflammatory gene expression, but not 18-kDa translocator protein binding, in rat pup brain after controlled cortical impact. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model. [2011]

6. England pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids and traumatic neurological injury: from neuroprotection to neuroplasticity? [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Concussions, Traumatic Brain Injury, and the Innovative Use of Omega-3s. [2017]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Omega-3 Fatty acids could alleviate the risks of traumatic brain injury - a mini review. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Omega-3 polyunsaturated fatty acid supplementation improves neurologic recovery and attenuates white matter injury after experimental traumatic brain injury. [2021]