Fish Oil Supplementation, Resting Energy Expenditure, Skeletal Muscle Membrane Composition and Metabolism in Elderly Subjects.

Effect of Fish Oil Supplementation on Resting Energy Expenditure, Skeletal Muscle Membrane Composition and Metabolism in Elderly Subjects.

Resting metabolic rate (RMR) declines by 1-2% per decade after 20 years of age. This reduction is linked to a decrease in fat free mass (FFM) (10-20%) and the rate of energy expenditure of tissues (Manini 2010).

It has also been shown that as we age there is a:

• Concomitant reduction in basal fat and carbohydrate oxidation, most likely due to the decrease in RMR than to a change in respiratory exchange ratio (RER) (St-Onge and Gallagher 2010).
• A change towards a more saturated membrane of different tissues (Rabini et al 2002).

Incorporation of omega-3s, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), into cell membranes may alter energy metabolism by:

• Increasing the rate at which proteins operate (Hulbert 2007).
• Promoting the release of EPA and DHA into the cytosol which will act as ligands for peroxisome proliferator-activated receptors (PPARs) (Calder 2011). PPARs play an important role in energy homeostasis by regulating genes involved in lipid metabolism (Kota et al 2005).
• Augmenting protein synthesis through activation of the mTOR-p70s6k pathway (Di Girolamo et al 2014).

Supplementation with fish oil in older males and females:

• Increases whole muscle phospholipid profile of EPA and DHA (Smith et al 2011).
• Increases lean body mass (LBM), RMR, and fatty acid oxidation (Logan et al unpublished)
• Decreases carbohydrate oxidation (Logan et al unplubished). Skeletal muscle (SM) accounts for 20-30% of RMR (Zurlo et al 1990, Manini 2010), therefore it is tempting to speculate that these changes may occur by some of the mechanisms described earlier, with skeletal muscle being an important contributor.

To date there are no studies that have examined the effect of n-3 supplementation (3g/day)* on plasma membrane fatty acid composition, RMR and substrate oxidation, and the possible mechanisms behind it.

Therefore the purpose of this study is to determine whether in older adults (female and male), supplementation with n-3 alters:

1. RMR and fatty acid oxidation.
2. Membrane composition of whole muscle and sarcolemma.
3. Content of skeletal muscle membrane fatty acid transport proteins.
4. Dose response of NaKATPase and SERCA efficiency
5. Content of mitochondrial proteins
6. Expression and content of PPARs and proteins involved in translocation of FA transporters (AMPK, ERK1/2, CamKII).
7. Phosphorylation of AMPKα(THR172), ERK1/2(THR202 TYR204) and CaMKII(THR286).
8. Proteomic profile of skeletal muscle.
9. Body composition

Study Overview

• Status: Unknown
• Conditions: Whole Body and Skeletal Muscle Energy Metabolism
• Intervention / Treatment: Dietary supplement: Omega-3 Complete; Dietary supplement: Placebo Pill

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1G 2W1
      • University of Guelph

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Between 60 and 75 years old
• Must currently practice a consistent diet and exercise regimen, and maintain this throughout the duration of the study

Exclusion Criteria:

• Have any medical condition (no evidence of significant cardiovascular disease or organ dysfunction, including hypertension, dyslipidemia, and diabetes mellitus), and hospitalization or surgeries
• Consume more than two meals of fish/wk and/or have taken an omega-3 supplement during the prior three months.
• Have a BMI > 30 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Fish Oil Capsules
Placebo Comparator: Placebo Pill; Oral ingestion of 3 capsules of a placebo olive oil pill (Swanson Health Products, PO Box 2803 - Fargo, ND 58108 USA) per day for 12 weeks.	Dietary supplement: Placebo Pill; Olive Oil Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in skeletal muscle whole muscle membrane fatty acid composition from baseline	Baseline and 12 weeks
Change in skeletal muscle sodium pump (Na/K ATPase) activity (umol/mg protein/hour)	Baseline and 12 weeks
Change in skeletal muscle sarcoplasmic reticulum calcium (SERCA) ATPase activity (umol/mg protein/hour)	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in whole body resting metabolic rate	Baseline, 6 and 12 weeks
Change in skeletal muscle membrane fatty acid transporter content	Baseline and 12 weeks
Change in skeletal muscle content of mitochondrial proteins	Baseline and 12 weeks
Change in skeletal muscle phosphorylation of AMPKα(THR172), ERK1/2(THR202 TYR204) and CaMKII(THR286)	Baseline and 12 weeks
Change in skeletal muscle PPARs content	Baseline and 12 weeks
Change in body composition	Baseline, 6 and 12 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Change in Whole Body Resting Fat Oxidation From Baseline	Baseline, 6 and 12 weeks
Change in Whole Body Resting Carbohydrate Oxidation From Baseline	Baseline, 6 and 12 weeks
Change in Fasted Blood Triglyceride Concentration From Baseline	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: University of Guelph

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: January 10, 2015
• First Submitted That Met QC Criteria: January 10, 2015
• First Posted (Estimate): January 14, 2015

Study Record Updates

• Last Update Posted (Actual): May 4, 2017
• Last Update Submitted That Met QC Criteria: May 1, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: University of Guelph