Fatty Acid Metabolism in Carriers of Apolipoprotein E Epsilon 4 Allele: Determining the Blood-to-brain Link
- Conditions
- Healthy
- Interventions
- Dietary Supplement: omega-3 phospholipidsDietary Supplement: omega-3 Triglycerides
- Registration Number
- NCT04279743
- Lead Sponsor
- Université de Sherbrooke
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 160
- Men and women aged between 30-50 years old.
- Tobacco use,
- Malnutrition (assessed from blood albumin, hemoglobin and lipids),
- Diabetes,
- Participants taking an EPA+DHA supplement or consuming more than 2 fish meals per week,
- Uncontrolled thyroid, renal and endocrine disorder disease,
- Chronic immune condition or inflammation (CRP > 10 mg/l, white cell count),
- Cancer,
- Recent major surgery or cardiac event,
- Pregnant or lactating women,
- Pre-menopause or menopause,
- Dementia,
- Ongoing or past severe drug or alcohol abuse,
- Psychiatric difficulties or major depression
- Ongoing or past intensive physical training.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ApoE4 carriers omega-3 phospholipids 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. ApoE4 non carriers omega-3 Triglycerides 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. ApoE4 carriers omega-3 Triglycerides 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. ApoE4 non carriers omega-3 phospholipids 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.
- Primary Outcome Measures
Name Time Method DHA levels in LPC and FFA baseline, 1, 2, 3, 4, 8 and 12 weeks after baseline To evaluate plasma DHA levels in lysophosphatidylcholine and free fatty acids by ApoE genotype and treatment intervention.
EPA levels in LPC and FFA baseline, 1, 2, 3, 4, 8 and 12 weeks after baseline To evaluate plasma EPA levels in lysophosphatidylcholine and free fatty acids by ApoE genotype and treatment intervention.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Centre de Recherche sur le Vieillissement
🇨🇦Sherbrooke, Quebec, Canada