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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if omega-3 fatty acids from fish oil can protect the brain from impacts, such as those experienced in soccer heading. Participants will take either omega-3 capsules or placebo capsules and undergo brain imaging and other health tests. The trial targets soccer players aged 18-30 with at least five years of heading experience who are willing to avoid activities involving head impacts during the study. It suits individuals with regular internet access who do not consume significant omega-3s or oily fish. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on brain protection.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that omega-3 fatty acids, such as DHA and EPA found in fish oil, are generally safe for people. Taking up to 5 grams a day is considered safe for most individuals. In animal studies, omega-3 supplements aided brain recovery after injury, suggesting potential benefits for humans. These fatty acids often support brain health and have been researched for their benefits in various conditions. Regarding safety, previous research indicates they are well-tolerated, with no major side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using omega-3 fatty acids for brain injury because these compounds, particularly DHA and EPA, are thought to support brain health and repair. Unlike standard treatments, which might include medications and therapies focusing on symptoms and inflammation, omega-3s provide a nutritional approach that may promote cellular repair and neuroprotection. The active ingredients, DHA and EPA, are derived from purified deep-sea fish oil, making the treatment rich in essential nutrients that are crucial for brain function. This innovative approach could offer a complementary or alternative option to existing treatments, potentially enhancing recovery outcomes for individuals with brain injuries.

What evidence suggests that Omega-3 Fatty Acids might be an effective treatment for brain injury?

Research has shown that omega-3 fatty acids, particularly DHA and EPA, might aid brain healing after an injury. Studies have found that these fatty acids can enhance brain tissue healing and improve cognitive skills in individuals with mild brain injuries. Omega-3s also appear to reduce the body's response to brain injuries, aiding recovery. Additionally, these fatty acids are known to decrease swelling, a common issue after a head injury. This trial will compare the effects of omega-3 supplements, specifically DHA and EPA, with a placebo to assess their potential benefits for individuals experiencing repeated head impacts, such as those from heading a soccer ball. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

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

Consuming oily fish (2 servings or more/month: salmon, bluefin, swordfish, anchovies)

Allergy to fish or shellfish

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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Postinjury supplementation with both DHA and EPA similarly reduced the injury response as measured by a similar set of brain health biomarkers (63). Despite ...

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Omega-3 Fatty Acids and Subconcussive Head Impacts

The purpose of the proposed study is to determine whether, and to what extent, supplementation with omega-3 fatty acids [docosahexaenoic acid (DHA) and ...

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Omega-3 fatty acids and vitamin D reportedly reduce inflammation, and in combination, might improve TBI outcomes. This study examined how an ...

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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 ...

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