Novel Nutrition Solutions for Sarcopenia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Sarcopenia

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Leucine-enriched protein
* Dietary Supplement: LC n-3 PUFA


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |