Impact of Fish Oil Dose on Tissue Content and Function

Impact of Omega (ω)-3 Polyunsaturated Fatty Acids (n-3 PUFA) Upon Blood, Muscle and Adipose Tissue Content and Function: Dosing and Washout Study

In this 5-month study, we will track the incorporation and washout of n-3 PUFA into different tissues following two different dosing strategies in healthy young and older volunteers. All groups will be followed for washout.

Data gathered from this study will be used to establish novel dosing strategies and provide insights into the incorporation of n-3 PUFAs in different tissues and their washout in young and older participants.

Study Overview

• Status: Completed
• Conditions: Sarcopenia; Aging; Muscle Atrophy
• Intervention / Treatment: Dietary supplement: Fish oil supplementation

Detailed Description

Skeletal muscle is crucial for health and accounts for approximately 40% of total body mass. A loss of skeletal muscle mass is seen in the process of ageing, with reductions between 0.2%-0.5% of muscle mass per year starting in the fifth decade. Accelerated loss of muscle and function above a certain threshold is characterized as sarcopenia. Age-related sarcopenia is prevalent in the UK; it is estimated to affect 4.6% men and 7.9% women with an average age of 67 years. Older people have an impaired capacity to increase muscle protein synthesis (MPS) rates in response to protein intake; this is thought to be a key contributor to age-related sarcopenia. Therefore, it is essential to elucidate new strategies to prevent and treat the accelerated loss of muscle mass and function.

Omega (ω)-polyunsaturated fatty acids (n-3 PUFAs) derived from fish oil have possible beneficial effects on health. Evidence suggests potential therapeutic effects of n-3 PUFAs in maintenance/prevention of loss of skeletal muscle mass. N-3 PUFAs probably exert their effects by incorporation into tissue membranes. However, the relation between dose and incorporation into tissue membranes is unclear. Interestingly, a higher dose ingested over 4 weeks seen by McGlory et al. induced similar omega-3 incorporation in the tissue compared to the low doses over 8 weeks studied by Smith et al. If higher doses change tissue composition earlier, then there will be earlier benefits for muscle health and function. Thus, there is a need to examine whether an initial loading dose incorporation into tissues can be sustained by moving to a lower maintenance feeding dose. Furthermore, the exact molecular mechanisms of how n-3 PUFAs act on skeletal muscle are unclear. Several metabolic and molecular responses are affected, but wherein these pathways n-3 PUFAs act remain largely unknown and requires more investigation, with a focus on long-term settings.

This study aims to tackle these problems by executing a 5-month study where we will track the incorporation and washout of n-3 PUFAs into different tissues following two different dosing strategies in healthy young and older volunteers. Data gathered from this study will be used to establish novel dosing strategies and provide insights into the incorporation of n-3 PUFAs in different tissues and their washout in young and older participants. Ultimately, these insights will help targeting, prevention, and treatment of sarcopenia.

Participating in this study requires approximately 30 hours of commitment, of which 12 hours will be spent in the lab.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Stirlingshire
    • Stirling, Stirlingshire, United Kingdom, FK9 4LA
      • University of Stirling

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Provide valid informed consent prior to any study procedure
• Males and females 18-35 years of age or 60+ years of age
• BMI between 18-29 kg/m2
• Free of musculoskeletal injuries
• Willing to avoid alcohol in the 48-h period prior to the visits
• Willing to sustain their current diet and lifestyle and not to make conscious changes for the duration of the study
• An omega-3 status of less than 20% seen in whole blood taken during the screening visit.
• Willing to sustain current use of supplementation/anti-depressants or other medication not interfering with the study results.
• Women: not currently pregnant, not intending to become pregnant in the coming 5 months or lactating.
• Women: willing to maintain current use of contraceptives or post-menopausal supplementation if any for the duration of the study.
• Not allergic to fish, shellfish, seaweed, iodine, anesthetics, nickel or chrome.

Exclusion Criteria:

• Smoker
• Adherence to a strict vegan/vegetarian diet
• Treatment for cardiovascular diseases or blood pressure >140/90 mmHg
• Any diseases or medication that cause fat malabsorption (intestine issues such as celiac disease, Crohn's disease,chronic pancreatitis, or cystic fibrosis; liver and biliary disease, diarrhoea, steatorrhea)
• Diabetes or other (metabolic) disease that induce muscle wasting
• Surgery in prior 6 months
• Currently being on FO supplementation
• Current participation in another clinical trial, or in a trial within the past month
• For women: pregnant, intention to get pregnant during the course of the study or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Young loading dose group; Participants (18-35) will receive a loading dose of fish oil supplementation during the first 4 weeks of the intervention period of the study. In the last 8 weeks participants will receive a maintenance dose of fish oil supplementation. The total amount of EPA/DHA received throughout the supplementation period will be the same as the old group.	Dietary supplement: Fish oil supplementation; Fish oil capsules.
Experimental: Old loading dose group; Participants (60y+) will receive a loading dose of fish oil supplementation during the first 4 weeks of the intervention period of the study. In the last 8 weeks participants will receive a maintenance dose of fish oil supplementation. The total amount of EPA/DHA received throughout the supplementation period will be the same as the young group.	Dietary supplement: Fish oil supplementation; Fish oil capsules.
Experimental: Young constant dose group; Participants (18-35y) will receive a constant dose of fish oil supplementation throughout the intervention period of the study. Total amount of EPA/DHA received throughout the 12 weeks supplementation period will be the same as the loading groups.	Dietary supplement: Fish oil supplementation; Fish oil capsules.
Experimental: Old constant dose group; Participants (60y+) will receive a constant dose of fish oil supplementation throughout the intervention period of the study. Total amount of EPA/DHA received throughout the 12 weeks supplementation period will be the same as the loading groups.	Dietary supplement: Fish oil supplementation; Fish oil capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Red blood cell lipid composition	Changes in red blood cell membrane lipid composition by collecting venous blood samples.	Screening, Baseline (0 weeks), 4 weeks, 6 weeks, 8 weeks, 12 weeks (post intervention), 14 weeks, 16 weeks, 20 weeks (post wash-out)
Skeletal muscle lipid composition	Changes in skeletal muscle lipid composition by performing a muscle tissue biopsy in the vastus lateralis.	Baseline (0 weeks), 4 weeks, 12 weeks (post-intervention), 20 weeks (post wash-out)
Adipose tissue lipid composition	Changes in adipose lipid composition by performing an adipose tissue biopsy in the abdominal region.	Baseline (0 weeks), 4 weeks, 12 weeks (post-intervention), 20 weeks (post wash-out)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle tissue biopsy muscle protein turnover markers	Secondary outcome from the skeletal muscle biopsy will focus on the measurement of the phosphorylation status of signaling proteins known to regulate protein synthesis and breakdown.	Baseline (0 weeks), 4 weeks, 12 weeks (post-intervention), 20 weeks (post wash-out)
Adipose tissue biopsy inflammation markers	Secondary outcome from the adipose tissue biopsy will focus on markers involved in inflammation (e.g. NF-kB, IL-6)	Baseline (0 weeks), 4 weeks, 12 weeks (post-intervention), 20 weeks (post wash-out)
Red blood cell lipid mediator markers	Secondary outcome measures from red blood cells will focus on mediators derived from lipid and changes in lipid mediator synthesis.	Baseline (0 weeks), 4 weeks, 12 weeks (post-intervention), 20 weeks (post wash-out)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition DEXA scan.	Body composition will be estimated using dual energy X-ray absorptiometry (DEXA) scan.	Baseline (0 weeks), 12 weeks (post-intervention), 20 weeks (post wash-out)
Subcutaneous fat determination.	Subcutaneous fat will be assessed with the sum of skinfold thicknesses from 8 sites, following the ISAK protocol.	Baseline (0 weeks), 12 weeks (post-intervention), 20 weeks (post wash-out)
Strength measures	Muscle strength is determined by performing the handgrip strength test.	Screening (baseline, 0 weeks), 8 weeks, 16 weeks.
Mobility measures	Muscle mobility is determined by performing the timed-up-and-go test.	Screening (baseline, 0 weeks), 8 weeks, 16 weeks.

Collaborators and Investigators

• Sponsor: University of Stirling
• Collaborators: Danone Nutricia Research
• Investigators: Principal Investigator: Milena Banic, Msc, University of Stirling; Study Director: Nidia Rodriguez-Sanchez, PhD, University of Stirling; Study Director: Stuart Galloway, PhD, University of Stirling; Study Director: Oliver Witard, PhD, King's College London; Study Director: Miriam van Dijk-Ottens, PhD, Danone Nutricia Research

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): June 15, 2023
• Study Completion (Actual): June 15, 2023

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: February 24, 2021
• First Posted (Actual): February 26, 2021

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Washout; Fish oil supplementation; Omega-3 polyunsaturated fatty acids; Dosing strategy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Sarcopenia; Muscular Atrophy
• Other Study ID Numbers: 280280

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No