Novel Nutrition Solutions for Sarcopenia (NUTRIMAL)

Novel Nutrition Solutions in Elderly at Risk of Sarcopenia: LC n-3 PUFA and Leucine Combinations

This study will examine the effect of leucine-enriched protein supplementation, alone and in combination with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), on muscle mass and function in older adults at risk of sarcopenia.

The investigators hypothesize that LC n-3 PUFA supplementation will further enhance the efficacy of the leucine-enriched protein.

Study Overview

• Status: Completed
• Conditions: Sarcopenia
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Leucine-enriched protein; Dietary supplement: LC n-3 PUFA

Detailed Description

The progressive loss of skeletal muscle mass and function with advancing age, termed sarcopenia, contributes substantially to disability, physical dependence, and mortality among older adults. Aging is associated with an attenuated muscle protein synthetic response to the ingestion of small to moderate protein doses compared to younger persons. Several studies have reported that the acute, postprandial muscle protein synthesis (MPS) response to a suboptimal protein dose is enhanced when the leucine content of the protein bolus is increased. This indicates that supplementing the lower-protein daily meals (i.e., breakfast and lunch) with leucine may represent a practical strategy to augment the MPS response to these meals and, subsequently, attenuate sarcopenic muscle mass loss over time. In addition, LC n-3 PUFA supplementation has been shown to enhance the MPS response to amino acid infusion older adults suggesting that combined leucine and LC n-3 PUFA supplementation be particularly effective for improving daily MPS, muscle mass and function in older adults.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland
    • University College Dublin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: ≥65 y
• Sex: males and females
• Low muscle mass (assessed via bioelectrical impedance analysis using cut-offs from Janssen, 2004) and/or low handgrip strength (< 30 kg men, <20kg women)

Exclusion Criteria:

• BMI >35 kg/m2
• Cancer - malignancy in the past 5 years
• Multiple Sclerosis, Parkinsons Disease
• Chronic kidney disease
• Liver failure
• Diabetes
• Conditions that will affect ability to consume, digest and/or absorb the study drink (i.e. cows milk protein allergy, inflammatory bowel disease)
• Smokers
• Cognitive function < 21 on Mini-Mental State Examination
• Excess alcohol intake
• Regular resistance training
• Total walking incapacity
• Musculoskeletal or neuromuscular impairments that could interfere with strength testing
• Medications interfering with muscle metabolism
• Adherence to a high energy or high protein diet three months before starting and during the study. Use of protein containing or amino acid containing nutritional supplements three months before starting and during the study.
• High consumers of oily fish.
• Weight change > 3 kg past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Protein-free, LC n-3 PUFA-free juice based supplement	Dietary supplement: Placebo; Protein-free, LC n-3 PUFA-free juice based supplement
Experimental: Leucine-enriched protein; Juice based supplement containing leucine-enriched protein	Dietary supplement: Leucine-enriched protein; Leucine-enriched whey protein
Experimental: Leucine-enriched protein + LC n-3 PUFA; Juice based supplement containing leucine-enriched protein and LC n-3 PUFA	Dietary supplement: Leucine-enriched protein; Leucine-enriched whey protein; Dietary supplement: LC n-3 PUFA; LC n-3 PUFA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appendicular skeletal muscle mass	Assessed via dual energy x-ray absorptiometry	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Isometric knee extension strength	Maximal voluntary contraction	6 months
Physical performance	Short physical performance battery, single leg stand, timed up and go	6 months
Metabolomics	Assessed using nuclear magnetic resonance (NMR) spectroscopy	6 months
Transcriptomics	Assessed via RNA Sequencing	6 months
Thigh muscle mass	Assessed in dominant leg via MRI in sub cohort (n=39)	6 months
Muscle protein synthesis	Measured as fractional synthetic rate (%/day) over a 3-d period at baseline and end of study	6 months

Collaborators and Investigators

• Sponsor: University College Dublin
• Investigators: Principal Investigator: Helen Roche, PhD, University College Dublin

Publications and helpful links

General Publications

• Murphy CH, Flanagan EM, De Vito G, Susta D, Mitchelson KAJ, de Marco Castro E, Senden JMG, Goessens JPB, Mikłosz A, Chabowski A, Segurado R, Corish CA, McCarthy SN, Egan B, van Loon LJC, Roche HM. Does supplementation with leucine-enriched protein alone and in combination with fish-oil-derived n-3 PUFA affect muscle mass, strength, physical performance, and muscle protein synthesis in well-nourished older adults? A randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2021 Jun 1;113(6):1411-1427. doi: 10.1093/ajcn/nqaa449.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): December 21, 2018
• Study Completion (Actual): December 21, 2018

Study Registration Dates

• First Submitted: February 3, 2018
• First Submitted That Met QC Criteria: February 3, 2018
• First Posted (Actual): February 12, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: NUTRIMAL-3; 14/F/822 (Other Grant/Funding Number: Department of Agriculture and Marine)

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
• product manufactured in and exported from the U.S.: No