NR Supplementation and Exercise

NCT04907110 | Completed

• 1 other identifier: NL77756.068.21
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The number of age-related chronic diseases (like obesity, type 2 diabetes and cardiovascular diseases) is increasing rapidly worldwide, reaching pandemic proportions. These age-related chronic diseases are associated with metabolic disturbances and mitochondrial dysfunction in humans. Nicotinamide adenosine dinucleotide (NAD) levels play an important role in energy metabolism and mitochondrial functioning and indeed it has been shown that high concentrations of NAD+ as well as a high NAD+/NADH ratio are strongly associated with metabolic and mitochondrial health. In contrast, decreased NAD+ bioavailability is reported in both ageing and obese humans as well as in diabetic mice. These findings fueled the idea of influencing NAD+ bioavailability in order to improve metabolic disturbances and mitochondrial dysfunction in humans. Supplementation with nicotinamide riboside (NR), a naturally occurring form of vitamin B3, may provide a way to boost 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. Recently, it has been suggested that a situation where NAD+ levels become limited, is needed for NR supplementation to exert beneficial health effects. This situation could be achieved by combining exercise and NR supplementation. However, studies combining NR and exercise are lacking, which is why we would like to perform such a study here.

Conditions

Overweight and Obesity; Aging; Type 2 Diabetes

Keywords

exercise; NR supplementation; NAD metabolism

Outcome Measures

Primary Outcomes (1)

• Ex vivo muscle mitochondrial function

  Ex vivo mitochondrial function in skeletal muscle measured by oxygen consumption in muscle fibres (muscle biopsy vastus lateralis) on lipid-derived and carbohydrate-derived substrates.

  Pre-intervention test day 3 + day 40 of the intervention NR/Placebo + exercise

Secondary Outcomes (12)

• Maximal aerobic capacity

  Pre-intervention test day 1 + Day 38

• Physical performance

  Pre-intervention test day 1 + Day 38

• Skeletal muscle NAD concentrations (ex-vivo)

  Pre-intervention test day 3 + Day 40

• Skeletal muscle NAD concentration (in-vivo)

  Pre-intervention test day 3 + Day 40

• Intrahepatic lipid content

  Pre-intervention test day 1 + Day 38

Study Arms (2)

Exercise + NR

EXPERIMENTAL

Participants will be asked to take two pills of NR (250mg/pill) twice daily (a total of 4 pills/day; 1000mg/day), for 40 days. During days 17-38 of the NR intervention, participants will perform a 3-weeks supervised exercise training program with four \~30 min exercise sessions per week (two endurance session on a bike at 70%Wmax and two high intensity interval (HIIT) sessions. To assess the outcomes, participants will undergo three test days before the start of the NR supplementation and repeat these three test days at the end (day 38-40) of NR supplementation.

Dietary Supplement: Niagen; Other: Exercise

Exercise + Placebo

PLACEBO COMPARATOR

Participants will be asked to take two pills of placebo, twice daily (a total of 4 pills/day), for 40 days. During days 17-38 of the intervention, participants will perform a 3-weeks supervised exercise training program with four \~30 min exercise sessions per week (two endurance session on a bike at 70%Wmax and two high intensity interval (HIIT) sessions. To assess the outcomes, participants will undergo three test days before the start of the NR supplementation and repeat these three test days at the end (day 38-40) of the placebo supplementation.

Other: Exercise

Interventions

Niagen DIETARY_SUPPLEMENT

Participants in the NR supplementation + exercise group will undergo oral NR supplementation for 40 days. NiagenTM is the name for the dietary supplement containing NR (ChromaDex, Inc. Irvine, USA). The total dosage of NR per day will be 1000mg. This supplementation time of 40 days 1000mg/day

Also known as: Nicotinamide Riboside (NR)

Exercise + NR

Exercise OTHER

During days 17-38 of the NR/placebo intake, participants will perform a 3-weeks supervised exercise training program with four \~30 min exercise sessions per week (two endurance session on a bike at 70%Wmax and two high intensity interval (HIIT) sessions.

Exercise + NR; Exercise + Placebo

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Participants are able to provide signed and dated written informed consent prior to any study specific procedures
• Aged ≥ 65 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

You may not qualify if:

• Type 2 diabetes
• 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
• Medication use known to hamper subject's safety during the study procedures
• Subjects who do not want to be informed about unexpected medical findings
• Use of food supplements containing NR or Resveratrol (similar working mechanisms)

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University

Maastricht, 6229 ER, Netherlands

Location

MeSH Terms

Conditions

Overweight; Obesity; Diabetes Mellitus, Type 2; Motor Activity

Interventions

nicotinamide-beta-riboside; Exercise

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and Investigator will be blinded for the study material (i.e. NR or placebo).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The present study is a randomized, double-blinded, placebo-controlled double arm longitudinal intervention study in a pre and post design.

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: May 28, 2021
• Study Start: August 10, 2021
• Primary Completion: December 2, 2022
• Study Completion: December 7, 2022
• Last Updated: February 10, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)