Insulin Resistance, Obesity
Conditions
Keywords
Nicotinamide Riboside, Obesity, Metabolic health, Insulin resistance, Mitochondrial function, Brown adipose tissue, Energy expenditure, Ectopic lipid accumulation, Cardiovascular risk, Acetylcarnitine
Brief summary
This study will investigate the effects of 6 week Nicotinamide Riboside supplementation (1000 mg/day) on metabolic health in healthy (pre)obese humans. The primary objective will be hepatic and whole body insulin sensitivity. Secondary objectives, to provide information about the underlying mechanism, will be muscle mitochondrial function, brown fat activity, ectopic lipid accumulation, energy metabolism, cardiovascular risk parameters, body composition and acetylcarnitine levels.
Interventions
DIETARY_SUPPLEMENTNicotinamide Riboside (Niagen)
DIETARY_SUPPLEMENTPlacebo
Sponsors
Dutch Heart Foundation
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent * Caucasian * Males and postmenopausal females * Aged 45-65 years at start of the study * Body mass index (BMI) 27 - 35 kg/m2 * Stable dietary habits (no weight loss or gain \>5kg in the past 3 months) * Sedentary lifestyle (not more than 2 hours of sports per week)
Exclusion criteria
* Type 2 diabetes * Active diseases (cardiovascular, diabetes, liver, kidney, cancer or other) * Contra-indication for MRI * Participation in earlier research or medical examination that included PET/CT scanning * Alcohol consumption of \>2 servings per day * Smoking in the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity: muscle- and liver specific | 6 weeks after supplementation | Hyperinsulinemic euglycemic clamp: Rate of glucose disappearance (Rd) will be calculated by using tracer kinetics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ectopic lipid accumulation | 6 weeks after supplementation | Liver and skeletal muscle lipid accumulation measured with H-MRS in vivo. |
| Brown adipose tissue activity | 6 weeks after supplementation | Subjects will be exposed to an individualized cooling protocol, after which an 18F-FDG PET/CT scan is made |
| Cardiovascular risk parameters | 6 weeks after supplementation | Cardiac energy status measured with P-MRS and Ambulatory blood pressure. |
| Muscle mitochondrial function (ex vivo) | 6 weeks after supplementation | Ex vivo mitochondrial function in skeletal muscle measured by oxygen consumption in muscle fibres (muscle biopsy vastus lateralis) on lipid-derived and carbohydrate-derived substrates. |
| Body composition | 6 weeks after supplementation | Fat mass and fat free mass measured with a BodPod. |
| Acetylcarnitine levels | 6 weeks after supplementation | Skeletal muscle acetylcarnitine levels measured with H-MRS in vivo, before and after exercise stimulation (cycling). |
| Whole body energy expenditure | 6 weeks after supplementation | Sleeping metabolic rate measured during an overnight stay in a respiration chamber. Resting metabolic rate measured with ventilated hood system, basal, during insulin stimulation (clamp) and during cold stimulation (cooling protocol BAT activity). |
Countries
Netherlands
Outcome results
None listed