Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype

Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype (NADMet)

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.

-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.

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