Nicotinamide Riboside Supplementation and Exercise Training to Promote Healthy Longevity

Boosting the NAD+ Levels in Older Individuals Via Nicotinamide Riboside Supplementation and Exercise Training to Promote Metabolic Health

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.

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)