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Do Apolipoprotein E Polymorphisms Influence Risk of Cognitive Decline by Modulating Omega-3 Fatty Acid Metabolism?

NCT01577004 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 40

Last updated 2012-04-13

No results posted yet for this study

Summary

BACKGROUND: Compared to the epsilon 2 or epsilon 3 alleles, the epsilon 4 allele of apolipoprotein E (ApoE4) is associated with twice the prevalence of late-onset Alzheimer's disease (AD). Epidemiological studies show that risk of AD varies inversely with consumption of omega-3 fatty acids from fish and seafood. Despite apparently lower fish intake in AD, pooled analysis of the literature shows that plasma and brain docosahexaenoic acid (DHA) is actually the same in AD as in healthy age-matched controls. Fish oil trials in AD are also not convincing. We recently shown that ApoE4 carriers have 41% higher fasting plasma EPA and DHA compared to non-carriers, but the plasma EPA and DHA response to fish oil in ApoE4 carriers was half that seen in non-carriers.

HYPOTHESES: (i) Carriers of ApoE4 have altered metabolism of carbon-13 (13C)-DHA as well as EPA and DHA provided in a dietary supplement. (ii) A dietary supplement of EPA+DHA will improve cognitive performance but only in non-carriers of ApoE4.

OBJECTIVES: In both carriers and non-carriers of ApoE4, to compare whether- i) ApoE4 alters incorporation of 13C-DHA into plasma lipids or its beta-oxidation.

ii) 13C-DHA metabolism changes while on a dietary supplement of EPA+DHA; iii) Better cognitive performance occurs while on EPA+DHA and is linked to raising plasma EPA and/or DHA.

EXPERIMENTAL METHODS: Participants older than 50 y old and not demented were enrolled. DHA metabolism was evaluated using both 13C-DHA and an EPA+DHA supplement (2.4 g/d for 5 mo; n = 20/gp). Before and in the last month of supplementation, plasma uptake and beta-oxidation of 50 mg of 13C-DHA was followed during one month. Blood omega-3 fatty acids was evaluated monthly during the supplementation period. Cognitive testing was performed before and 4 months after starting the omega-3 fatty acid supplement.

IMPLICATIONS: This project will help explain the apparent link that is newly emerging between ApoE polymorphisms, altered omega-3 fatty acid metabolism and risk of cognitive decline, and should help in the development of nutraceutical-based clinical trials using fish oil for the elderly.

Conditions

  • Healthy

Interventions

DIETARY_SUPPLEMENT

omega-3 fatty acid

Subjects will be given four 1 g capsules of fish oil providing 1.4 g/d of EPA and 1.0 g/d of DHA as ethyl esters (Ocean Nutrition, Dartmouth, NS), which is similar to the dose used in previous studies with MCI and AD (20, 21).

Sponsors & Collaborators

  • Université de Sherbrooke

    lead OTHER

Principal Investigators

  • Melanie Plourde, Ph.D. · Université de Sherbrooke

Study Design

Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
50 Years
Max Age
90 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2009-07-31
Primary Completion
2011-10-31
Completion
2011-10-31

Countries

  • Canada

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01577004 on ClinicalTrials.gov