Clinical trial NCT02338401: Fish Oil Supplementation, Resting Energy Expenditure, Skeletal Muscle Membrane Composition and Metabolism in Elderly Subjects.
Official title: Effect of Fish Oil Supplementation on Resting Energy Expenditure, Skeletal Muscle Membrane Composition and Metabolism in Elderly Subjects.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Whole Body and Skeletal Muscle Energy Metabolism
Lead sponsor: University of Guelph
Sponsor class: OTHER
First posted: 2015-01-14
Enrollment: 30
Sex: ALL
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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* Increases lean body mass (LBM), RMR, and fatty acid oxidation (Logan et al unpublished)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


Eligibility criteria: 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

Primary outcomes:
measure: Change in skeletal muscle whole muscle membrane fatty acid composition from baseline
timeFrame: Baseline and 12 weeks
measure: Change in skeletal muscle sodium pump (Na/K ATPase) activity (umol/mg protein/hour)
timeFrame: Baseline and 12 weeks
measure: Change in skeletal muscle sarcoplasmic reticulum calcium (SERCA) ATPase activity (umol/mg protein/hour)
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in whole body resting metabolic rate
timeFrame: Baseline, 6 and 12 weeks
measure: Change in skeletal muscle membrane fatty acid transporter content
timeFrame: Baseline and 12 weeks
measure: Change in skeletal muscle content of mitochondrial proteins
timeFrame: Baseline and 12 weeks
measure: Change in skeletal muscle phosphorylation of AMPKα(THR172), ERK1/2(THR202 TYR204) and CaMKII(THR286)
timeFrame: Baseline and 12 weeks
measure: Change in skeletal muscle PPARs content
timeFrame: Baseline and 12 weeks
measure: Change in body composition
timeFrame: Baseline, 6 and 12 weeks
Other outcomes:
measure: Change in Whole Body Resting Fat Oxidation From Baseline
timeFrame: Baseline, 6 and 12 weeks
measure: Change in Whole Body Resting Carbohydrate Oxidation From Baseline
timeFrame: Baseline, 6 and 12 weeks
measure: Change in Fasted Blood Triglyceride Concentration From Baseline
timeFrame: Baseline and 12 weeks
Locations:
city: Guelph
country: Canada
facility: University of Guelph
state: Ontario
Study officials:
References: