Aging
Conditions
Keywords
Nicotinamide Riboside, Nicotinamide Adenine Dinucleotide, Skeletal muscle, Metabolism
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.
Interventions
DIETARY_SUPPLEMENTNicotinamide Riboside
OTHERPlacebo
Sponsors
University of Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
70 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Skeletal muscle NAD+ levels in vastus lateralis biopsy using targeted metabolomics | Following 3 weeks of NR supplementation | — |
Secondary
| Measure | Time frame |
|---|---|
| Muscle Arterio-Venous Difference - Tissue-specific metabolite trafficking, oxygen consumption and CO2 production | Following 3 weeks of NR supplementation |
| Muscle biopsy: adaptive expression profile (genomic) | Following 3 weeks of NR supplementation |
| Improvement in response to oral glucose tolerance test/HOMA-IR | 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 |
| Muscle strength - grip testing | Following 3 weeks of NR supplementation |
| Changes in resting metabolic rate using indirect calorimetry | Following 3 weeks of NR supplementation |
| Improvement in lipid profile | Following 3 weeks of NR supplementation |
Countries
United Kingdom
Contacts
Primary ContactYasir Elhassan, MRCP
Backup ContactGareth Lavery, PhD
Outcome results
None listed