Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD(+) Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures

Elhassan YS, Kluckova K, Fletcher RS, Schmidt MS, Garten A, Doig CL · Cell Reports

The rare human trial that biopsied the target tissue. What rose in muscle was nicotinic acid adenine dinucleotide and nicotinamide clearance products rather than NAD+ itself, the authors taking NAAD as the more sensitive marker of NAD+ metabolism; whole-blood NAD+ more than doubled. Muscle mitochondrial respiration was unchanged on high-resolution respirometry and glycolytic enzyme levels were unchanged, while the muscle transcriptome moved down, not up, on energy-metabolism and mitochondrial pathways. Circulating inflammatory cytokines fell.

Population

Aged men

Intervention

Nicotinamide riboside 1,000 mg/day for 21 days, crossover

Comparator

Placebo

Limitations

Twelve men aged 70-80, 21 days. It establishes that oral NR reaches aged human muscle by way of a marker of NAD+ metabolism rather than by a rise in muscle NAD+ itself, and measures of muscle and whole-body metabolism were unchanged. No equivalent study has ever sampled human cartilage or synovium after an NAD+ precursor.