The Effect of Omega-3 Fatty Acid Supplementation on Skeletal Muscle Membrane Composition and Cellular Metabolism

Study Overview
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Brief Summary
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The biological membranes that surround a cell and its organelles are vital to the overall function of the cell. Fatty acids are the main structural component of membranes, and the presence of specific fatty acids can alter a membrane's characteristics, which subsequently alters function. Two fatty acids that are of particular interest to researchers are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These omega-3 fatty acids have unique unsaturated structures, and their incorporation into biological membranes appear to elicit potent physiological effects. The body is unable to intrinsically synthesize these important fatty acids, so they must be obtained from the diet or through supplementation. Compared to research investigating other body tissues, the effect of EPA and DHA on skeletal muscle membranes and cellular function has received little attention. Of the studies done, EPA and DHA supplementation consistently results in increased EPA, DHA, and total omega-3 fatty acid content in the skeletal muscle membranes of rodents. One study has also demonstrated this effect in humans. These studies, however, have been limited to whole muscle measurements, yet cells contain numerous subcellular membranes with diverse functions. Two membranes of key importance to the metabolic function of a skeletal muscle cell are the membrane that surrounds the cell (plasma membrane), and the membrane that surrounds the mitochondria. The plasma and mitochondrial membranes are responsible for taking up nutrients and converting them into useable energy for the muscle. Recent findings suggest that physiological changes in these processes may occur following EPA and DHA supplementation. At rest and during exercise, there is potential for a shift in substrate selection that favors fat utilization following EPA and DHA supplementation. Several membrane proteins are responsible for transporting fat into the cell and mitochondria. The presence of EPA and DHA within membranes has the potential to affect the membrane integration and function of proteins. The investigators aim to determine whether fat utilization increases following EPA and DHA supplementation, and if there is a concurrent change in the concentrations of fat transport proteins within plasma and mitochondrial membranes. Supplementation with EPA and DHA may also affect oxygen consumption, an important process in energy production that is regulated by mitochondrial membrane proteins. Evidence from human and rodent studies shows a decrease in whole body oxygen consumption following supplementation. The investigators aim to examine these changes directly by measuring mitochondrial respiration following EPA and DHA supplementation. Therefore, the primary purpose of this study is to examine how plasma and mitochondrial membrane fatty acid composition change individually in response to EPA and DHA supplementation in humans. The secondary purpose of this study is to examine functional metabolic changes that occur in skeletal muscle in response to EPA and DHA supplementation, and to investigate correlational relationships between these changes and any compositional alterations in plasma and mitochondrial membranes. The investigators hypothesize that supplementation with EPA and DHA will alter fuel selection at rest and during exercise, and this will correspond to an increase in the concentration of membrane fatty acid transport proteins, and that these changes will correlate to an increase in the EPA, DHA, and total omega-3 content of plasma and mitochondrial membranes.

Official Title
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The Effect of Omega-3 Fatty Acid Supplementation on Skeletal Muscle Plasma and Mitochondrial Membrane Composition and Cellular Metabolism

Conditions
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Skeletal Muscle Energy Metabolism

Intervention / Treatment
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* Dietary Supplement: Omega-3 Complete
* Dietary Supplement: Placebo Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recreationally active Must currently practice a consistent diet, and exercise regimen, and maintain this throughout the duration of the study Exclusion Criteria: Current or previous supplementation with omega-3s Average fish intake greater than two times per week Sedentary Highly active/trained Diagnosed respiratory problem Diagnosed heart problem/condition Lightheadedness, shortness of breath, chest pain, numbness, fatigue, coughing, or wheezing during at rest of with low to moderate physical activity Cardiovascular disease risk factors: Family history of heart attacks, hypertension, hypercholesterolemia, diabetes mellitus, smoking, obesity Allergies to lidocaine, fish/fish oil, gelatine, glycerin, or mixed tocopherols Currently taking any medications or supplements that may increase the chance of bleeding (e.g. Aspirin, Coumadin, Anti-inflammatories, Plavix, Vitamin C or E, high doses of garlic, ginkgo biloba, willow bark products) Tendency toward easy bleeding or bruising

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omega-3 Complete<br>Oral ingestion of 3000 mg (5 capsules) of Omega-3 Complete (Jamieson Laboratories Ltd., Windsor, Ontario, Canada) per day for 12 weeks | Dietary Supplement: Omega-3 Complete<br> <br> |
| Placebo Comparator: Placebo Pill<br>Oral ingestion of 5 capsules of a placebo oil pill (Jamieson Laboratories Ltd., Windsor, Ontario, Canada) per day for 12 weeks | Dietary Supplement: Placebo Pill<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in skeletal muscle whole muscle membrane fatty acid composition from baseline | Percent change in the content of whole muscle membrane fatty acids | Baseline and 12 weeks | 
| Change in skeletal muscle plasma membrane fatty acid composition from baseline | Percent change in the content of plasma membrane fatty acids | Baseline and 12 weeks | 
| Change in skeletal muscle mitochondrial membrane composition from baseline | Percent change in the content of mitochondrial membrane fatty acids | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in whole body resting fat oxidation from baseline |  | Baseline and 12 weeks | 
| Change in whole body resting carbohydrate oxidation from baseline |  | Baseline and 12 weeks | 
| Change in whole body sub-maximal exercise fat oxidation from baseline |  | Baseline and 12 weeks | 
| Change in whole body sub-maximal exercise carbohydrate oxidation from baseline |  | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skeletal Muscle, Eicosapentaenoic acid, Docosahexaenoic acid, Exercise, Membrane Composition, Lipid Metabolism, Omega-3