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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NR+EXTR | Experimental | This arm will ingest NR orally and perform exercise training |
|
| PLA+EXTR | Placebo Comparator | This arm will ingest placebo orally and perform exercise training |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nicotinamide Riboside (NR) | Dietary Supplement | Participants will ingest 1g/d of NR orally during 12 weeks in parallel to a exercise training program |
|
| Measure | Description | Time Frame |
|---|---|---|
| Skeletal muscle mitochondrial respiratory capacity | Skeletal muscle mitochondrial respiratory capacity will be measured in permeabilized fibres. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Quantification of proteins that regulate oxidative metabolism | Quantification of proteins content of oxidative phosphorylation system in muscle biopsies | 12 weeks |
| Skeletal muscle mitochondrial content |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rodrigo Mancilla, PhD | Contact | +56953676588 | rmancilla@uft.cl |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Finis Terrae University | Recruiting | Santiago | Santiago Metropolitan | Chile |
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| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D008659 | Metabolic Diseases |
| ID | Term |
|---|---|
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C018613 | nicotinamide-beta-riboside |
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Double blinded
| Placebo | Dietary Supplement | Participants will ingest 1g/d of placebo orally during 12 weeks in parallel to a exercise training program |
|
Proteins content of oxidative phosphorylation system will be quantified from muscle biopsy
| 12 weeks |
| Maximal aerobic capacity | Maximal aerobic capacity will be measure upon a progressive cycling test | 12 weeks |
| Walking speed and distance | Walking speed and distance will be measured via the 6-minutes walking test | 12 weeks |
| Seating and standing transitions | Time spent on performing seating and standing transitions will be measured upon the timed-up and go test | 12 weeks |
| Exercise efficiency | Exercise efficiency will be measured upon a sub maximal cycling test and indirect calorimetry | 12 weeks |
| Intrahepatic liver fat content | Intrahepatic liver fat content will be measured by 1H-MRS | 12 weeks |
| Body weight | body weight will be measured in kilograms | 12 weeks |
| Total muscle mass | total muscle mass will be measured in kilograms and/or percentage | 12 weeks |
| Total fat mass | Total fat mass will be measured in kilograms and/or percentage | 12 weeks |
| Fat-free mass | Fat-free mass will be measured in kilograms and/or percentage | 12 weeks |
| NAD+ levels | NAD+ levels in circulation and in skeletal muscle | 12 weeks |
| 24h Blood pressure | 24h Blood pressure will be measured with a continuous blood pressure holder device | 12 weeks |
| Resting energy expenditure | Resting energy expenditure will be measured by indirect calorimetry | 12 weeks |