Healthy Aging, Lifestyle-related Condition, Metabolic Diseases
Conditions
Brief 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.
Interventions
DIETARY_SUPPLEMENTNicotinamide Riboside (NR)
Participants will ingest 1g/d of NR orally during 12 weeks in parallel to a exercise training program
DIETARY_SUPPLEMENTPlacebo
Participants will ingest 1g/d of placebo orally during 12 weeks in parallel to a exercise training program
Sponsors
Finis Terrae University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blinded
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skeletal muscle mitochondrial respiratory capacity | 12 weeks | Skeletal muscle mitochondrial respiratory capacity will be measured in permeabilized fibres. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Quantification of proteins that regulate oxidative metabolism | 12 weeks | Quantification of proteins content of oxidative phosphorylation system in muscle biopsies |
| 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 |
| Body weight | 12 weeks | body weight will be measured in kilograms |
Countries
Chile
Contacts
Primary ContactRodrigo Mancilla, PhD
Outcome results
None listed