NR Supplementation and Exercise

NCT ID: NCT04907110

Last Updated: 2023-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-10
• Study Completion Date: 2022-12-07

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.

Detailed Description

Rationale: 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.

Objective: The primary objective of this study is to determine whether combined treatment of exercise and NR imposes greater improvements in skeletal muscle mitochondrial metabolism in older humans compared to exercise treatment alone. The secondary objective is to determine whether combined treatment of exercise and NR supplementation imposes greater improvements in sleeping metabolic rate (SMR). As explorative objectives, we will examine whether combined treatment with exercise and NR imposes greater improvements in muscle (NAD) metabolites, energy metabolism and physical performance.

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

Study population: 30 older male and (postmenopausal) female participants, aged 65 - 80 years with a BMI between 25-35 kg/m2 will perform this study (15 participants in the exercise+placebo group, 15 participants in the exercise+NR group). From experience with similar studies, we estimate a drop-out rate of 20% and a screening failure of 50% (due to the strict inclusion criteria), resulting in maximally 36 subjects that have to be included and 72 subjects that have to be screened (maximally).

Intervention (if applicable): Participants will be asked to take two pills of NR (250mg/pill), or placebo, twice daily (two with breakfast and two with diner, 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. Participants will be randomly assigned to the placebo + exercise or NR + exercise arm. 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.

Main study parameters/endpoints: The primary study endpoints is ex vivo skeletal muscle mitochondrial function measured via high-resolution respirometry. Explorative objectives are muscle (NAD) metabolites, energy metabolism and physical performance.

Conditions

Overweight and Obesity; Aging; Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Exercise + NR

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.

Group Type: EXPERIMENTAL

Niagen

Intervention Type: 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

Exercise

Intervention Type: 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 + Placebo

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.

Group Type: PLACEBO_COMPARATOR

Exercise

Intervention Type: 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.

Interventions

Niagen

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

Intervention Type: DIETARY_SUPPLEMENT

Exercise

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.

Intervention Type: OTHER

Other Intervention Names

Nicotinamide Riboside (NR)

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Maastricht University

Maastricht, , Netherlands

Countries

Netherlands

Other Identifiers

NL77756.068.21

Identifier Type: -

Identifier Source: org_study_id