Does Incorporation of EPA and DHA in Lipoproteins Differ According to Apolipoprotein E Genotype?
Genetics and nutrition both clearly affect the risk of Alzheimer's disease (AD) in the elderly. Apolipoprotein E (APOE4) is the most important known genetic risk for AD and is prevalent in 20-25% of Canadians, but at present, knowing an individual's ApoE genotype does not help the diagnosis, treatment or prevention of AD. Furthermore, fish intake containing docosahexaenoic acid (DHA, 22:6 omega-3) and eicosapentaenoic acid (EPA, 20:5 omega-3) may be incorporated as a prevention strategy for lowering the risk of AD. However, fish intake seems not to protect APOE4 carriers from developing AD. One explanation as to why APOE4 carriers may not benefit from fish intake is potentially linked with imbalances in omega-3 fatty acid metabolism. The investigators recently reported that after 3g/d of EPA+DHA for 6 weeks, increases in the two fatty acids was less for carriers resulting in a significant gene-by-diet interaction. ApoE is a component of lipoproteins and ApoE genotypes modulate the fasting lipoprotein response to fish-oil supplementation. Therefore, the investigators hypothesis is that APOE4 genotype is associated with imbalances in lipoprotein concentrations which has the consequence to be associated with imbalances in EPA and DHA transport. The investigators will recruit and test 100 healthy young adults since at older ages carriers of ApoE4 usually take medication altering their lipoprotein profile. They will receive an EPA + DHA supplement for one month. This period was chosen because the 3 class of lipoproteins (VLDL, LDL and HDL) have different concentrations in TG, phospholipids and cholesteryl esters and to fully investigate lipoprotein fatty acid changes, one month of supplementation is needed to change EPA and DHA in all lipid classes. The investigators will monitor the distribution of EPA and DHA in the lipoproteins over a one month supplementation with fish oil and the investigators will separate the investigators groups by APOE4 carriers and non-carriers.
|Study Design:||Endpoint Classification: Bio-availability Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Does Incorporation of EPA and DHA in Lipoproteins Differ According to Apolipoprotein E Genotype?|
- Distribution of EPA and DHA in lipoproteins by APOE genotype [ Time Frame: Once each week for 28 days ] [ Designated as safety issue: No ]We will measure % and concentration of EPA and DHA in VLDL, HDL and LDL to evaluate how these fatty acids are transported in the blood and whether APOE genotype changes the distribution of these fatty acids.
|Study Start Date:||February 2011|
|Study Completion Date:||May 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Experimental: APOE4 carriers
The results obtained for APOE4 carriers will be compared to the one obtained from APOE4 non-carriers. Carriers are defined as being at least carrier of one APOE4 allele.
Dietary Supplement: omega-3 fatty acids
Participants will take 700 mg/d of EPA and 500 mg/d of DHA as ethyl esters for one month (Ocean Nutrition, Dartmouth, NS) which is about 10 times the current estimated intake of young adults (21). This corresponds to one capsule with breakfast and one capsule with diner.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01544855
|Centre de recherche sur le vieillissement|
|Sherbrooke, Quebec, Canada, J1H4C4|