Nicotinamide Riboside Supplementation and Exercise Training to Promote Healthy Longevity

NCT06425042 — Not applicable, Recruiting, 28 participants, Finis Terrae University

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

Registry	NCT06425042, acronym RESTORENAD
Status	Recruiting
Phase	Not applicable
Study type	Interventional; randomized, parallel, masking: double, treatment
Enrollment	28 (Estimated)
Sponsor	Finis Terrae University (Other)
Conditions	Healthy Aging, Lifestyle-related Condition, Metabolic Diseases
Interventions	Nicotinamide Riboside (NR), Placebo (Dietary supplement)
Dates	start 2024-03-01, primary completion 2025-12-01 (estimated), completion 2026-03-01 (estimated), first posted 2024-05-22, last updated 2025-07-11
Locations	1 site in Chile

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
NR+EXTR	Experimental	Dietary Supplement: Nicotinamide Riboside (NR)	This arm will ingest NR orally and perform exercise training
PLA+EXTR	Placebo comparator	Dietary Supplement: Placebo	This arm will ingest placebo orally and perform exercise training

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

+Outcome measures

Primary outcomes

Skeletal muscle mitochondrial respiratory capacity [12 weeks]: Skeletal muscle mitochondrial respiratory capacity will be measured in permeabilized fibres.

Secondary outcomes

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

+Eligibility

Sex: All, ages: 60 Years to 80 Years, accepts healthy volunteers

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)

+Locations (1)

Facility	City	Country	Status
Finis Terrae University	Santiago, Santiago Metropolitan	Chile	Recruiting