Nicotinamide Riboside Supplementation and Exercise Training to Promote Healthy Longevity

Healthy Aging Clinical Trial

— RESTORENAD  

Official title:

Boosting the NAD+ Levels in Older Individuals Via Nicotinamide Riboside Supplementation and Exercise Training to Promote Metabolic Health

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06425042
• Other study ID #: 23-041
• Status: Recruiting
• Phase: N/A
• Start date: March 1, 2024
• Est. completion date: March 2026

Study information

• Verified date: May 2024
• Source: Finis Terrae University
• Contact: Rodrigo Mancilla, PhD
• Phone: +56953676588
• Email: rmancilla[@]uft.cl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The prevalence of age-related chronic diseases (like obesity, type 2 diabetes and cardiovascular diseases) is mounting worldwide, reaching pandemic proportions. These age-related chronic diseases are associated with diminished skeletal muscle mitochondrial function in humans. Nicotinamide adenosine dinucleotide (NAD) is a coenzyme that regulates mitochondrial function, therefore, plays an important role in energy metabolism. Importantly, it has been shown that high cellular NAD+ levels as well as a high NAD+/NADH ratio promote metabolic and mitochondrial health. In contrast, NAD+ bioavailability declines upon aging in humans as well as in animal models of metabolic disorders and type 2 diabetes. These findings fuel the notion of boosting the NAD+ bioavailability in order to improve metabolic disturbances and mitochondrial dysfunction in aged individuals. Supplementation with nicotinamide riboside (NR), a naturally occurring form of vitamin B3, boosts cellular NAD+ levels. However, in contrast to animal studies, NR supplementation in humans has so far been unsuccessful in improving skeletal muscle mitochondrial function, exercise capacity or insulin sensitivity. Interestingly, Recently, it has been suggested that metabolic conditions where NAD+ levels become limited, is needed for NR supplementation to exert beneficial health effects. This metabolic condition could be achieved by exercise. However, studies combining NR and exercise are lacking, and that is why we will perform the present study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: March 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

• Participants are able to provide signed and dated written informed consent prior to any study specific procedures
• Aged = 60 and = 80 years
• Body mass index (BMI) 25 - 35 kg/m2
• Stable dietary habits (no weight loss or gain > 5 kg in the past 3 months)
• No signs of active cardiovascular disease, liver or kidney malfunction

Exclusion Criteria:

• Patients with congestive heart failure and and/or severe renal and or liver insufficiency
• Uncontrolled hypertension
• Any contra-indication for MRI scanning
• Alcohol consumption of > 3 servings per day for man and >2 servings per day for woman
• Smoking
• Unstable body weight (weight gain or loss > 5kg in the last 3 months)
• Engagement in structured exercise activities > 2 hours a week
• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator which would possibly hamper our study results
• Use of food supplements containing NR or Resveratrol (similar working mechanisms)

Related Conditions & MeSH terms

• Healthy Aging
• Lifestyle-related Condition
• Metabolic Diseases

Intervention

Dietary Supplement:
• Nicotinamide Riboside (NR)
Participants will ingest 1g/d of NR orally during 12 weeks in parallel to a exercise training program
• Placebo
Participants will ingest 1g/d of placebo orally during 12 weeks in parallel to a exercise training program

Locations

Country	Name	City	State
Chile	Finis Terrae University	Santiago	Region Metropolitana

Sponsors (1)

Lead Sponsor	Collaborator
Finis Terrae University

Country where clinical trial is conducted

Chile, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Skeletal muscle mitochondrial respiratory capacity	Skeletal muscle mitochondrial respiratory capacity will be measured in permeabilized fibres.	12 weeks
Primary	Skeletal muscle mitochondrial content	Proteins content of oxidative phosphorylation system will be quantified from muscle biopsy	12 weeks
Secondary	Quantification of proteins that regulate oxidative metabolism	Quantification of proteins content of oxidative phosphorylation system in muscle biopsies	12 weeks
Secondary	Maximal aerobic capacity	Maximal aerobic capacity will be measure upon a progressive cycling test	12 weeks
Secondary	Walking speed and distance	Walking speed and distance will be measured via the 6-minutes walking test	12 weeks
Secondary	Seating and standing transitions	Time spent on performing seating and standing transitions will be measured upon the timed-up and go test	12 weeks
Secondary	Exercise efficiency	Exercise efficiency will be measured upon a sub maximal cycling test and indirect calorimetry	12 weeks
Secondary	Intrahepatic liver fat content	Intrahepatic liver fat content will be measured by 1H-MRS	12 weeks
Secondary	Body weight	body weight will be measured in kilograms	12 weeks
Secondary	Total muscle mass	total muscle mass will be measured in kilograms and/or percentage	12 weeks
Secondary	Total fat mass	Total fat mass will be measured in kilograms and/or percentage	12 weeks
Secondary	Fat-free mass	Fat-free mass will be measured in kilograms and/or percentage	12 weeks
Secondary	NAD+ levels	NAD+ levels in circulation and in skeletal muscle	12 weeks
Secondary	24h Blood pressure	24h Blood pressure will be measured with a continuous blood pressure holder device	12 weeks
Secondary	Heart rate variability	Heart rate variability will be measured with a continuos electrocardiogram monitor device	12 weeks
Secondary	Resting energy expenditure	Resting energy expenditure will be measured by indirect calorimetry	12 weeks