Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype
- Conditions
- Aging
- Interventions
- Dietary Supplement: Nicotinamide RibosideOther: Placebo
- Registration Number
- NCT02950441
- Lead Sponsor
- University of Birmingham
- Brief Summary
This study is designed to assess the physiological consequences of elevating Nicotinamide Adenine Dinucleotide (NAD+) availability using Nicotinamide Riboside (NR) supplementation in skeletal muscle tissue, and examine its effect upon muscle metabolic phenotype.
- Detailed Description
-NAD+ sensitive metabolic decline in ageing, including sarcopenia, leads to a reduction in energy metabolism, contribute to chronic inflammation, disposing individuals to metabolic disease and overall decreased later-life health. Prominent metabolic changes include a decline in NAD+ content and deterioration in muscle NAD+ mediated signalling and mitochondrial function, ultimately compromising skeletal muscle and whole body energy homeostasis.
The most efficient means to boost NAD+ in muscle appears to be oral delivery of NR, and participants will be supplemented with 1000mg NR (2x x250mg tablets twice daily) for 3 weeks.
* Hypothesis: elevating skeletal muscle NAD+ bioavailability using NR supplementation will increase markers of mitochondrial function and that will manifest as a more favourable metabolic profile.
* Study Setting: the study will be carried out at the NIHR/Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital Birmingham.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 12
- Male sex
- Age 70-80 years
- BMI 20-30kg/m2
- Participants who are able to discontinue aspirin for 3 days prior to the muscle biopsy
- Participants who are able to discontinue statins and vitamin D supplements for a week before the second visit and for the duration of the study
- Serious active medical conditions including inflammatory diseases or malignancies
- Significant past medical history including diabetes mellitus, ischaemic heart disease, cerebrovascular disease, significant respiratory disease requiring medication, epilepsy
- High blood pressure (BP>160/100mmHg)
- Oral Anticoagulants (like Warfarin, Dabigatran, Rivaroxaban) or Clopidogrel therapy which will increase the risk of bruising following a muscle biopsy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Nicotinamide Riboside Nicotinamide Riboside 1000mg (2x250mg tablets twice daily) Placebo Placebo Two tablets twice daily
- Primary Outcome Measures
Name Time Method Skeletal muscle NAD+ levels in vastus lateralis biopsy using targeted metabolomics Following 3 weeks of NR supplementation Mitochondrial function assessment in skeletal muscle using high resolution respirometry Following 3 weeks of NR supplementation Mitochondrial function assessment on muscle biopsies using high resolution respirometry
- Secondary Outcome Measures
Name Time Method Improvement in lipid profile Following 3 weeks of NR supplementation 24 hour urine collection - NAD+ metabolomics and changes in steroid ratios using Gas chromatography/ mass spectrometry Following 3 weeks of NR supplementation Improvement in response to oral glucose tolerance test/HOMA-IR Following 3 weeks of NR supplementation Muscle Arterio-Venous Difference - Tissue-specific metabolite trafficking, oxygen consumption and CO2 production Following 3 weeks of NR supplementation Changes in resting metabolic rate using indirect calorimetry Following 3 weeks of NR supplementation Muscle strength - grip testing Following 3 weeks of NR supplementation Muscle biopsy: adaptive expression profile (genomic) Following 3 weeks of NR supplementation
Trial Locations
- Locations (1)
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, West Midlands, United Kingdom