Fatty Acid Metabolism in Carriers of Apolipoprotein E Epsilon 4 Allele: Determining the Blood-to-brain Link

Summary

In Canada, \~17 millions of adults between 30-64 y old could benefit from a prevention strategy to lower the risk of Alzheimer's disease (AD). Although a lot of epidemiological studies reported positive cognitive outcomes in populations eating fish, there is skepticism about the link between docosahexaenoic acid (DHA), an omega-3 (OM3) fatty acid in fish and prevention of cognitive decline. This is largely because there is a disconnect between epidemiological, molecular and animal studies which generally favor a link between higher DHA intake and cognition whereas clinical DHA and fish oil trial seem not to support such as link. There are several knowledge gaps in this field that might explain why clinical trials were not successful. This project will focus on two major gaps : OM3 fatty acid metabolism and the blood-to-brain DHA link. OM3 supplements in cardiovascular disease have faced the same issues for decades but the more recent trials have now generated the clinical evidence supporting primary and secondary cardiovascular events reduction and a better risk to benefit balance of OM3 drugs compared to statins, for instance. What if, for cognitive decline, the target was missed because the supplement/drug formulations were not appropriately designed to target the brain? The investigators hypothesize that (i) E4 carriers display a faulty packaging of circulating OM3, leading to reduced bioavailability for brain cells, (ii) The use of new OM3 formulation can direct plasma DHA into brain compartments more readily available for the brain, thereby increasing brain DHA concentrations and improving cognition. Studies in mice and humans will be performed to test OM3 metabolism and the blood-to-brain DHA link. Ultimately the information generated in this research project will help to better design clinical trials in term of fatty acid formulation, expected level to reach in the plasma and the brain.

Conditions

• Healthy

Interventions

DIETARY_SUPPLEMENT

omega-3 phospholipids

The intervention is a randomized double blind parallel design testing the metabolism of a krill oil omega-3 phospholipid supplement compared to fish oil omega-3 triglycerides in carriers and non-carriers of the ApoE4 allele. Half of the carriers and non-carriers will receive phospholipids and the other half will receive triglycerides. The intervention choice will be randomized and double blind. Participants will be instructed to take 4 supplements every day (2 in the morning and 2 in the evening) (4 g/ day of phospholipids), providing 1.8 g/day of omega-3 fatty acids. They will come back fasted to the research center on weeks 0, 1, 2, 3, 4, 8 and 12 of the study for blood draws. The omega-3 fatty acids metabolism will be compared between the carriers and non carriers of the ApoE4 allele.

DIETARY_SUPPLEMENT

omega-3 Triglycerides

The intervention is a randomized double blind parallel design testing the metabolism of a krill oil omega-3 phospholipid supplement compared to fish oil omega-3 triglycerides in carriers and non-carriers of the ApoE4 allele. Half of the carriers and non-carriers will receive phospholipids and the other half will receive triglycerides. The intervention choice will be randomized and double blind. Participants will be instructed to take 4 supplements every day (2 in the morning and 2 in the evening), providing 1.8 g/day of omega-3 fatty acids. They will come back fasted to the research center on weeks 0, 1, 2, 3, 4, 8 and 12 of the study for blood draws. The omega-3 fatty acids metabolism will be compared between the carriers and non carriers of the ApoE4 allele.

Sponsors & Collaborators

• Université de Sherbrooke

  lead OTHER

Principal Investigators

• Melanie Plourde, PhD · Université de Sherbrooke

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

30 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-08-01

Primary Completion

2025-04-01

Completion

2025-04-01

Countries

• Canada

Study Locations