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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
28
Participants will ingest 1g/d of NR orally during 12 weeks in parallel to a exercise training program
Participants will ingest 1g/d of placebo orally during 12 weeks in parallel to a exercise training program
Finis Terrae University
Santiago, Santiago Metropolitan, Chile
RECRUITINGSkeletal muscle mitochondrial respiratory capacity
Skeletal muscle mitochondrial respiratory capacity will be measured in permeabilized fibres.
Time frame: 12 weeks
Quantification of proteins that regulate oxidative metabolism
Quantification of proteins content of oxidative phosphorylation system in muscle biopsies
Time frame: 12 weeks
Skeletal muscle mitochondrial content
Proteins content of oxidative phosphorylation system will be quantified from muscle biopsy
Time frame: 12 weeks
Maximal aerobic capacity
Maximal aerobic capacity will be measure upon a progressive cycling test
Time frame: 12 weeks
Walking speed and distance
Walking speed and distance will be measured via the 6-minutes walking test
Time frame: 12 weeks
Seating and standing transitions
Time spent on performing seating and standing transitions will be measured upon the timed-up and go test
Time frame: 12 weeks
Exercise efficiency
Exercise efficiency will be measured upon a sub maximal cycling test and indirect calorimetry
Time frame: 12 weeks
Intrahepatic liver fat content
Intrahepatic liver fat content will be measured by 1H-MRS
Time frame: 12 weeks
Body weight
body weight will be measured in kilograms
Time frame: 12 weeks
Total muscle mass
total muscle mass will be measured in kilograms and/or percentage
Time frame: 12 weeks
Total fat mass
Total fat mass will be measured in kilograms and/or percentage
Time frame: 12 weeks
Fat-free mass
Fat-free mass will be measured in kilograms and/or percentage
Time frame: 12 weeks
NAD+ levels
NAD+ levels in circulation and in skeletal muscle
Time frame: 12 weeks
24h Blood pressure
24h Blood pressure will be measured with a continuous blood pressure holder device
Time frame: 12 weeks
Resting energy expenditure
Resting energy expenditure will be measured by indirect calorimetry
Time frame: 12 weeks
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