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

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

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.

Study Overview

• Status: Completed
• Conditions: Muscle Injury
• Intervention / Treatment: Other: Placebo (twice daily); Other: Nicotinamide Riboside/Pterostilbene (500 mg/100 mg twice daily)

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Other: Placebo (twice daily); Matching placebo
EXPERIMENTAL: Nicotinamide Riboside + Pterostilbene	Other: Nicotinamide Riboside/Pterostilbene (500 mg/100 mg twice daily); Elysium Basis TM, Elysium Health, Inc., NY, USA

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: University of Copenhagen

Publications and helpful links

General Publications

• Jensen JB, Dollerup OL, Moller AB, Billeskov TB, Dalbram E, Chubanava S, Damgaard MV, Dellinger RW, Trost K, Moritz T, Ringgaard S, Moller N, Treebak JT, Farup J, Jessen N. A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals. JCI Insight. 2022 Oct 10;7(19):e158314. doi: 10.1172/jci.insight.158314.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 12, 2019
• Primary Completion (ACTUAL): September 1, 2020
• Study Completion (ACTUAL): September 1, 2020

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 22, 2018
• First Posted (ACTUAL): November 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: AU2018-11-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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