Nicotinamide Riboside and Metabolic Health

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Nicotinamide Riboside on Metabolic Health in (Pre)Obese Humans

Conditions
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Obesity, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: Nicotinamide Riboside (Niagen)
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotinamide Riboside<br>Supplementation of Nicotinamide Riboside (Niagen) of 1000 mg/day for 6 weeks. 2 capsules in the morning together with breakfast and 2 capsules around noon together with lunch. Each capsule contains 250 mg. | Dietary Supplement: Nicotinamide Riboside (Niagen)<br> <br> Dietary Supplement: Placebo<br> <br> |
| Placebo Comparator: Placebo<br>Supplementation of Placebo of 1000 mg/day for 6 weeks. 2 capsules in the morning together with breakfast and 2 capsules around noon together with lunch. Each capsule contains 250 mg. | Dietary Supplement: Nicotinamide Riboside (Niagen)<br> <br> Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity: muscle- and liver specific | Hyperinsulinemic euglycemic clamp: Rate of glucose disappearance (Rd) will be calculated by using tracer kinetics. | 6 weeks after supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle mitochondrial function (ex vivo) | 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. | 6 weeks after supplementation | 
| Ectopic lipid accumulation | Liver and skeletal muscle lipid accumulation measured with H-MRS in vivo. | 6 weeks after supplementation | 
| Brown adipose tissue activity | Subjects will be exposed to an individualized cooling protocol, after which an 18F-FDG PET/CT scan is made | 6 weeks after supplementation | 
| Cardiovascular risk parameters | Cardiac energy status measured with P-MRS and Ambulatory blood pressure. | 6 weeks after supplementation | 
| Whole body energy expenditure | 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). | 6 weeks after supplementation | 
| Body composition | Fat mass and fat free mass measured with a BodPod. | 6 weeks after supplementation | 
| Acetylcarnitine levels | Skeletal muscle acetylcarnitine levels measured with H-MRS in vivo, before and after exercise stimulation (cycling). | 6 weeks after supplementation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotinamide Riboside, Obesity, Metabolic health, Insulin resistance, Mitochondrial function, Brown adipose tissue, Energy expenditure, Ectopic lipid accumulation, Cardiovascular risk, Acetylcarnitine