Impact of Fish Oil Dose on Tissue Content and Function

Aging Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04772040
• Other study ID #: 280280
• Status: Completed
• Phase: N/A
• Start date: November 1, 2021
• Est. completion date: June 15, 2023

Study information

• Verified date: December 2023
• Source: University of Stirling
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: June 15, 2023
• Est. primary completion date: June 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Muscle Atrophy
• Muscular Atrophy
• Sarcopenia

Intervention

Dietary Supplement:
• Fish oil supplementation
Fish oil capsules.

Locations

Country	Name	City	State
United Kingdom	University of Stirling	Stirling	Stirlingshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Stirling	Danone Nutricia Research

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Other	Strength measures	Muscle strength is determined by performing the handgrip strength test.	Screening (baseline, 0 weeks), 8 weeks, 16 weeks.
Other	Mobility measures	Muscle mobility is determined by performing the timed-up-and-go test.	Screening (baseline, 0 weeks), 8 weeks, 16 weeks.
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)