Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans

Study Overview
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Brief Summary
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Successful skeletal muscle regeneration depends on a functional pool of muscle stem cells, termed satellite cells (SC). SC are in a quiescent state throughout adulthood, but undergo multiple cycles of proliferation and self-renewal in response to muscle damage. During aging, there is a loss of SC quiescence, and SC more readily enter an ageing-state impairing their function. Animal studies have revealed a common denominator for increasing SC function and activity, namely Sirtuin activation. Natural stimulators of Sirtuins includes Nicotinamide Riboside (NR) (a Nicotinamide adenine dinucleotide (NAD+) precursor) and the polyphenol Pterostilbene (PT). In this study, we aim to investigate if NR+PT supplementation will promote skeletal muscle regeneration after muscle damage in elderly humans by enhanced recruitment of SC.

Detailed Description
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14 days after start of placebo or NR/PT (500/100 mg twice daily) supplementation a muscle damage will induced in the m. vastus lat. by electric stimulation combined with eccentric work in a dynamometer. Muscle biopsies will be collected at 2 hours, 2, 8 and 30 days post damage and placebo or NR/PT supplementation will continue for the whole study period (45 days).

Official Title
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Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans - A Randomized, Placebo-controlled, Clinical Trial

Conditions
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Muscle Injury

Intervention / Treatment
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* Other: Placebo (twice daily)
* Other: Nicotinamide Riboside/Pterostilbene (500 mg/100 mg twice daily)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written signed consent Age: 55-80 BMI: 20-28 (kg/(m2)) Non-smoker Exclusion Criteria: Endocrine disease, neurological or muscle disease Other severe disease High daily activity level (>30 min / day)

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo (twice daily)<br>* Matching placebo<br>|
| Experimental: Nicotinamide Riboside + Pterostilbene<br> | Other: Nicotinamide Riboside/Pterostilbene (500 mg/100 mg twice daily)<br>* Elysium Basis TM, Elysium Health, Inc., NY, USA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of Satellite Cells | quantified by immunohistochemistry in muscle biopsies | Change from baseline up to 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activation of Satellite cells | determined by immunohistochemistry and FACS | Change from baseline up to 45 days | 
| Presence of macrophages | determined by immunohistochemistry and FACS | Change from baseline up to 45 days | 
| Presence of Fibro/Adipogenic Progenitors | quantified by FACS | Change from baseline up to 45 days | 
| Presence of damaged muscle fibers | determined by immunohistochemistry | Change from baseline up to 45 days | 
| Presence of muscle regenerative fibers | determined by immunohistochemistry | Change from baseline up to 45 days | 
| Presence of autophagy in relation to muscle damage | determined by Western blot and PCR | Change from baseline up to 45 days | 
| Lipid accumulation in skeletal muscle tissue and liver | determined by magnetic resonance spectroscopy | Change from baseline to 8 days | 
| Blood glucose response in relation to muscle damage | determined by Continuous glucose monitoring | Change from baseline to 8 days | 
| Body composition (lean body mass and fat body mass) | measured by Dual energy X-ray absorptiometry | Change from baseline to 45 days | 
| Muscle strength | determined from maximal voluntary contraction of the m. quadriceps femoris | Change from baseline up to 45 days |