Effect of an Alpha-linolenic Acid-rich Supplement on Ketogenesis and Plasma Fatty Acids

Study Overview
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Brief Summary
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Background: As the main alternative fuel to glucose for the brain, increased plasma ketones could potentially help compensate for brain glucose hypometabolism occurring during aging. The precursor long-chain n-3 polyunsaturated fatty acid (PUFA), α-linolenic acid (ALA), is normally mostly β-oxidized and so could potentially be used to stimulate ketogenesis in humans. Objective: To compare the impact of an ALA-rich supplement on the ketogenic response in young and older healthy adults. Design: Ten young and ten older adults will consume a flaxseed oil supplement providing 2 g/d of ALA for 4 weeks. Plasma ketones, free fatty acids, triglycerides, glucose and insulin will be measured over 6 h during two metabolic study days, one before and one at the end of the supplementation. Hypothesis: ALA-rich supplement for 4 weeks will increase ketone production in both groups.

Official Title
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Effect of an Alpha-linolenic Acid-rich Supplement on Ketogenesis and Plasma n-3 Polyunsaturated Fatty Acids in Young Compared to Older Adults

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: alpha-linolenic acid-rich supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged between 18 and 30 or 65 years and more Exclusion Criteria: non smoker pregnancy or breastfeeding diabetes or insulin resistance uncontrolled thyroid disease, hepatic or renal disease uncontrolled high blood pressure medical treatment influencing lipid or glucide metabolism ongoing or past severe drug or alcohol abuse dementia or psychiatric difficulties or depression chronic immune condition or inflammation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Dietary Supplement: alpha-linolenic acid-rich supplement
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4 week ALA treatment<br>Participants will receive the alpha-linolenic acid-rich supplement (1000mg 4 times par day) for 4 weeks | Dietary Supplement: alpha-linolenic acid-rich supplement<br>* each participant consumed one 1000 mg capsule of flaxseed oil four times per day for 4 weeks, providing a total of 2 g/d of ALA. The capsules used were a commercially available flaxseed oil supplement containing ALA at 56% of total fatty acids (Jamieson, Toronto, ON, Canada). The other main fatty acids present in flaxseed oil include linoleic acid (18%), oleic acid (16%), palmitic and stearic acid (10% combined).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ketone Production | Total Ketone (acetoacetate + beta-hydroxybutyrate) concentration in plasma in average during the metabolic study day, measured hourly between 1 and 6h after breakfast | After 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Glucose | Glucose measured in plasma in average during the metabolic study day, measure hourly between 0 and 6 h after breakfast | After 4 weeks | 
| Plasma Triglycerides | Triglycerides measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast | After 4 weeks | 
| Plasma Free Fatty Acids | Free fatty acids measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast | 4 weeks | 
| Insulin Concentration in Plasma | Insulin measured in plasma in average during the metabolic study day, measured hourly between 0 ans 6 h after breakfast | after 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketone, α-linolenic acid, flaxseed, aging, β-hydroxybutyrate, acetoacetate, omega-3 fatty acids, ketogenesis