Omega-3 for Brain Fog

(NBF-MG01 Trial)

Recruiting at 1 trial location

Overseen By Anne-Julie Landry, Clinical Project Manager, M.Sc, DESS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Samuel Fortin

Disqualifiers: Fish allergy, Omega-3 use, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

48 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 using omega-3 supplements, you must stop them at least 30 days before the study starts.

What evidence supports the effectiveness of the treatment Omega-3 for Brain Fog?

Research shows that omega-3 fatty acids, including eicosapentaenoic acid (EPA), can improve learning, memory, and overall brain health. Long-term use of omega-3 supplements has been linked to a reduced risk of cognitive decline and Alzheimer's disease. ^{1 2 3 4 5}

Is omega-3 safe for human use?

Omega-3 fatty acids, including eicosapentaenoic acid (EPA), are generally considered safe and well-tolerated in humans. They have been shown to be risk-free and beneficial for brain health, with no significant safety concerns reported in studies. ^{1 6 7 8 9}

How does the drug Monoglyceride Eicosapentaenoic acid (omega-3) differ from other treatments for brain fog?

Monoglyceride Eicosapentaenoic acid (omega-3) is unique because it can be converted into docosahexaenoic acid (DHA) in the liver, which is crucial for brain health. This conversion helps maintain DHA levels in the brain, potentially supporting cognitive function and addressing symptoms like brain fog, unlike other treatments that may not directly influence brain lipid composition. ^{5 6 10 11 12}

What is the purpose of this trial?

A growing body of studies shows that omega-3s act directly in molecular signaling pathways that reduce inflammation and are thought to have a positive effect on cognitive health. Brain fog is a term that has been popularized in the medical world in the wake of the COVID-19 pandemic. A significant proportion of patients with long COVID reported having cognitive sequelae that were like fogginess. It is defined as a cognitive impairment with characteristic symptoms including problems with concentration, attention and memory, confusion, difficulty understanding what others are saying, reduced mental acuity and mental fatigue. These are episodes of reduced cognitive capacity that are not representative of the person's normal state. This condition can be caused by various factors such as stress, lack of sleep, overwork, depression, hormonal changes due to pregnancy or menopause in women, head injuries, migraine, certain diseases or viral infections, certain medications as well as substance abuse (alcohol and/or street drugs). In this study, we want to test whether omega-3 monoglycerides (MAG-EPA) can alter the cognitive health of people with brain fog.

Eligibility Criteria

This trial is for individuals experiencing 'brain fog' with symptoms like trouble concentrating, memory issues, and mental fatigue. It's not specified who can't join the trial, but typically those with certain medical conditions or taking medications that could interfere might be excluded.

Inclusion Criteria

Participant having no difficulty in swallowing tablets, capsules or gelcaps

Participant who obtains a mean score on the BFS screening questionnaires (BFS1 and BFS2) total of at least 30 and/or who obtains the following minimum score on at least one of the three factors: Factor 1 of at least 15 and/or Factor 2 of at least 15 and/or Factor 3 of at least 12

I am between 19 and 55 years old.

Exclusion Criteria

Presence of dependence on drugs of abuse or alcohol (˃ 3 units of alcohol per day, acute or chronic excessive consumption)

Participant included in another clinical study and who is receiving an investigational product or other research treatment

Known allergy or intolerance to fish or history of allergic reactions attributable to fish, or to a compound similar to fish oil

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment Phase 1

Participants receive MAG-EPA treatment at 1.5g/day for 8 weeks

8 weeks

4 visits (in-person), 3 visits (telephone follow-up)

Wash-out

Participants undergo a wash-out period with no treatment

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Monoglyceride Eicosapentaenoic acid (omega-3)

Trial Overview The study tests if omega-3 monoglycerides (MAG-EPA), which may reduce inflammation and improve cognitive health, can help people with brain fog. Participants will also receive sunflower oil as a comparison.

Participant Groups

Group I: Phase 2: MAG-EPA treatment group Experimental Treatment 1 Intervention

This phase of the study is a parallel design. Subjects will be assigned to experimental treatment (MAG-EPA) by randomization. Every subject in this arm will receive the same treatment at 1,5g/day for a period of 16 weeks.

Group II: Phase 1: Exploratory MAG-EPA treatment group Experimental Treatment 1 Intervention

This is a single arm phase of the study. Every subject will receive the experimental treatment (MAG-EPA) at 1,5g/day for a period of 8 weeks.

Group III: Phase 2: Placebo group Placebo Group 1 Intervention

This phase of the study is a parallel design. Subjects will be assigned to Placebo treatment (sunflower oil) by randomization. Every subject will receive the same treatment at 2,0g/day for a period of 16 weeks.

Monoglyceride Eicosapentaenoic acid (omega-3) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vascepa for:

• Hypertriglyceridemia
• Heart disease
• Depression

Approved in European Union as Eicosapentaenoic acid for:

• Hypertriglyceridemia
• Heart disease

Approved in Canada as MAG-EPA for:

• General health and wellness
• Heart health

Who Is Running the Clinical Trial?

Samuel Fortin

Lead Sponsor

Trials

3

Recruited

90+

Institut de recherche clinique du littoral (IRCL)

Collaborator

Trials

3

Recruited

100+

Findings from Research

A systematic review of nine randomized clinical trials involving 1319 participants found that omega-3 fatty acids significantly enhance cognitive functions such as learning and memory, as well as improve blood flow in the brain.

Omega-3 treatments were shown to be well-tolerated and risk-free, making them a beneficial option, especially for individuals who are lonelier, elderly, or have diets low in healthy omega-3 sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Omega-3 Polyunsaturated Fatty Acids on Brain Functions: A Systematic Review. Dighriri, IM., Alsubaie, AM., Hakami, FM., et al.[2022]

Observational studies suggest that higher intake of fish or DHA is linked to lower cognitive impairment, but intervention studies in healthy older adults have not shown significant benefits from EPA and DHA supplementation over two years.

While supplementation with EPA and DHA appears to have positive effects in individuals with mild cognitive impairment, it does not seem to benefit those with established Alzheimer's disease, indicating that timing and patient selection may be crucial for efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ω-3 fatty acids in the prevention of cognitive decline in humans. Cederholm, T., Salem, N., Palmblad, J.[2023]

Alzheimer's disease (AD) is linked to lower levels of omega-3 fatty acids, particularly DHA, in both plasma and specific brain regions, indicating a potential dietary influence on the disease.

The study found significant differences in fatty acid profiles between individuals with AD, mild cognitive impairment (MCI), and those with no cognitive impairment (NCI), suggesting that altered fatty acid metabolism may play a role in the progression of cognitive decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. Cunnane, SC., Schneider, JA., Tangney, C., et al.[2022]

Long-term use of omega-3 fatty acid supplements was associated with a 64% reduced risk of developing Alzheimer's disease in a study of 1,135 participants over 6 years.

A meta-analysis of 48 studies involving over 103,000 participants indicated that dietary intake of omega-3 fatty acids could lower the risk of all-cause dementia or cognitive decline by approximately 20%, particularly highlighting the benefits of docosahexaenoic acid (DHA).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Wei, BZ., Li, L., Dong, CW., et al.[2023]

A study using Long Evans rats showed that eicosapentaenoic acid (EPA) significantly contributes to the turnover of docosahexaenoic acid (DHA) in the brain, indicating its potential role in maintaining brain DHA levels.

After 8 weeks of dietary intervention, EPA was primarily converted to phosphatidylethanolamine (PE) in the liver and accumulated in the brain, suggesting that EPA supplementation could be beneficial for brain health and possibly for managing symptoms of major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma unesterified eicosapentaenoic acid is converted to docosahexaenoic acid (DHA) in the liver and supplies the brain with DHA in the presence or absence of dietary DHA. Metherel, AH., Rezaei, K., Lacombe, RJS., et al.[2021]

Alzheimer's disease is linked to imbalances in brain lipids and the accumulation of amyloid-β, which leads to neuronal damage and cognitive decline.

Medium chain fatty acids (MCFAs) and omega-3 polyunsaturated fatty acids (ω-3-PUFAs) may help improve brain health by reducing amyloid-β deposition and oxidative stress, potentially benefiting patients with mild cognitive impairment and Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Medium Chain and Polyunsaturated ω-3-Fatty Acids on Amyloid-β Deposition, Oxidative Stress and Metabolic Dysfunction Associated with Alzheimer's Disease. Mett, J.[2021]

Omega-3 polyunsaturated fatty acids (PUFAs) have been linked to various health benefits, including positive effects on cardiovascular disease, diabetes, and mental health conditions like depression, based on numerous epidemiological studies.

Despite the reported benefits, there are ongoing debates regarding the efficacy of omega-3 PUFAs for certain health outcomes, highlighting the need for further research to clarify their role in human health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 Polyunsaturated Fatty Acids and Their Health Benefits. Shahidi, F., Ambigaipalan, P.[2019]

The 2010 NIH State of the Science Conference found insufficient evidence to recommend any primary prevention therapy for Alzheimer's disease, including omega-3 fatty acids (n-3 LC-PUFA), despite public interest and use.

Epidemiological data suggest that low intake of n-3 LC-PUFA is associated with a higher risk of cognitive decline, but clinical trials have not specifically targeted these at-risk populations, indicating a gap in research that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease. Dacks, PA., Shineman, DW., Fillit, HM.[2021]

A lower concentration of eicosapentaenoic acid (EPA) in the blood was identified as a significant risk factor for ischemic stroke in a study involving 130 participants (65 with stroke and 65 controls).

The study also found that a lower EPA/arachidonic acid (AA) ratio and lower body mass index were significant risk factors specifically for the cardioembolism subtype of ischemic stroke, suggesting that monitoring these factors could help in stroke prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of eicosapentaenoic acid concentrations in plasma between patients with ischemic stroke and control subjects. Ikeya, Y., Fukuyama, N., Kitajima, W., et al.[2022]

Diets lacking omega-3 polyunsaturated fatty acids (PUFA) can significantly disrupt brain function, but these effects can often be reversed by reintroducing omega-3 PUFA, highlighting their importance for neural health.

Recent clinical studies suggest that omega-3 PUFA, particularly docosahexaenoic acid (DHA), may be beneficial in treating neuropsychological disorders like depression, with complex mechanisms of action beyond just affecting cell membrane properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega 3 fatty acids and the brain: review of studies in depression. Sinclair, AJ., Begg, D., Mathai, M., et al.[2007]

Observational studies suggest that omega-3 fatty acids, particularly DHA, may have beneficial effects on cognition and could help prevent Alzheimer's disease, although results are inconsistent.

Recent randomized studies did not show overall positive effects of omega-3 fatty acids on cognitive decline, but some individuals with mild Alzheimer's may benefit, indicating that these fatty acids could serve as an adjuvant therapy in specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are omega-3 fatty acids options for prevention and treatment of cognitive decline and dementia? Cederholm, T., Palmblad, J.[2013]

Mice fed a canola:soybean oil diet showed significant changes in brain fatty acid profiles, including increased oleic acid and docosahexaenoic acid (DHA), which are linked to improved neuronal function in the entorhinal cortex.

This dietary change resulted in enhanced neuronal firing activity and shorter action potentials, suggesting that canola oil-based diets may positively influence learning and memory by modifying the intrinsic properties of neurons in the entorhinal-hippocampal circuit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary intake of unsaturated fatty acids modulates physiological properties of entorhinal cortex neurons in mice. Arsenault, D., Julien, C., Chen, CT., et al.[2018]

References

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

Effects of Omega-3 Polyunsaturated Fatty Acids on Brain Functions: A Systematic Review. [2022]

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

ω-3 fatty acids in the prevention of cognitive decline in humans. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. [2022]

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

The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Plasma unesterified eicosapentaenoic acid is converted to docosahexaenoic acid (DHA) in the liver and supplies the brain with DHA in the presence or absence of dietary DHA. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Impact of Medium Chain and Polyunsaturated ω-3-Fatty Acids on Amyloid-β Deposition, Oxidative Stress and Metabolic Dysfunction Associated with Alzheimer's Disease. [2021]

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

Omega-3 Polyunsaturated Fatty Acids and Their Health Benefits. [2019]

8. France pubmed.ncbi.nlm.nih.gov

Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease. [2021]

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

Comparison of eicosapentaenoic acid concentrations in plasma between patients with ischemic stroke and control subjects. [2022]

10. China pubmed.ncbi.nlm.nih.gov

Omega 3 fatty acids and the brain: review of studies in depression. [2007]

11. England pubmed.ncbi.nlm.nih.gov

Are omega-3 fatty acids options for prevention and treatment of cognitive decline and dementia? [2013]

12. England pubmed.ncbi.nlm.nih.gov

Dietary intake of unsaturated fatty acids modulates physiological properties of entorhinal cortex neurons in mice. [2018]