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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by University of Guelph
Sponsor:
Collaborators:
McMaster University
Medical University of Bialystok
Information provided by (Responsible Party):
Lawrence Spriet, University of Guelph
ClinicalTrials.gov Identifier:
NCT01732003
First received: November 17, 2012
Last updated: November 27, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention
Skeletal Muscle Energy Metabolism
Dietary Supplement: Omega-3 Complete
Dietary Supplement: Placebo Pill

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: The Effect of Omega-3 Fatty Acid Supplementation on Skeletal Muscle Plasma and Mitochondrial Membrane Composition and Cellular Metabolism

Resource links provided by NLM:


Further study details as provided by University of Guelph:

Primary Outcome Measures:
  • Change in skeletal muscle whole muscle membrane fatty acid composition from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Percent change in the content of whole muscle membrane fatty acids

  • Change in skeletal muscle plasma membrane fatty acid composition from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Percent change in the content of plasma membrane fatty acids

  • Change in skeletal muscle mitochondrial membrane composition from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Percent change in the content of mitochondrial membrane fatty acids


Secondary Outcome Measures:
  • Change in whole body resting fat oxidation from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole body resting carbohydrate oxidation from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole body sub-maximal exercise fat oxidation from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole body sub-maximal exercise carbohydrate oxidation from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change in resting heart rate from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in sub-maximal exercise heart rate from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in sub-maximal exercise blood free fatty acid concentration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in sub-maximal exercise blood glucose concentration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in sub-maximal exercise blood lactate concentration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in resting blood C-reactive protein concentration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in resting blood cholesterol concentration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in resting blood high-density lipoprotein concentration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in resting blood low-density lipoprotein concentration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in resting blood cholesterol:high-density lipoprotein ratio from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in resting blood triacylglyceride concentration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in resting blood membrane fatty acid content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in skeletal muscle mitochondrial content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole muscle fatty acid translocase (FAT/CD36) content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole muscle plasma membrane fatty acid binding protein (FABPpm) content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole muscle fatty acid transport protein 1 (FATP1) content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole muscle fatty acid transport protein 4 (FATP4) content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole muscle pyruvate dehydrogenase content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in whole muscle 4-Hydroxynonenal content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in plasma membrane fatty acid translocase (FAT/CD36) content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in plasma membrane fatty acid binding protein (FABPpm) content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in plasma membrane fatty acid transport protein 1 (FATP1) content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in mitochondrial membrane fatty acid translocase (FAT/CD36) content from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in mitochondrial respiration from baseline [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: November 2011
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omega-3 Complete
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
Placebo Comparator: Placebo Pill
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

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01732003

Contacts
Contact: Christopher J Gerling, BScH 1-519-821-4120 ext 53907 cgerling@uoguelph.ca
Contact: Jamie Whitfield, BA 1-519-821-4120 ext 53907 jwhitfie@uoguelph.ca

Locations
Canada, Ontario
University of Guelph Recruiting
Guelph, Ontario, Canada, N1G 2W1
Sponsors and Collaborators
University of Guelph
McMaster University
Medical University of Bialystok
Investigators
Principal Investigator: Lawrence L Spriet, PhD University of Guelph
  More Information

Publications:
Responsible Party: Lawrence Spriet, Professor and Chair, University of Guelph
ClinicalTrials.gov Identifier: NCT01732003     History of Changes
Other Study ID Numbers: 11SE032
Study First Received: November 17, 2012
Last Updated: November 27, 2012
Health Authority: Canada: Ethics Review Committee

Keywords provided by University of Guelph:
Omega-3
Skeletal Muscle
Eicosapentaenoic acid
Docosahexaenoic acid
Exercise
Membrane Composition
Lipid Metabolism

ClinicalTrials.gov processed this record on October 21, 2014