Table 2.

Findings from clinical studies investigating effects of NR on skeletal muscle and CV systems

Study (Year)	Population and age	Dose	Length	Key findings related to intervention	Limitations
Dollerup et al. (2019)(36)	40 (20: NR treated) Caucasian males, insulin-resistant, obese (58±2 years old)	2000 mg/day	12 weeks	No change of NAD+ metabolites in skeletal muscle; ↓ NAMPT; no change in SIRT3 levels and activity; no effect on glucose metabolism in skeletal muscle; no effect on mitochondrial abundance and activity in skeletal muscle; no effect on lipid deposition in skeletal muscle	- Small sample size - Only white male subjects - Low generalizability - No measure of physical performance
Elhassan et al. (2019)(35)	12 old males (median age: 75 years old)	1000 mg/day	21 days	Well tolerability; no adverse events; ↑ NAD+ metabolites in skeletal muscle; ↓ expression of genes involved in energy metabolism in skeletal muscle; no effect on mitochondrial abundance and activity in muscle; no effect on hand-grip strength; no effect on forearm muscle blood flow; no effect on muscle glucose uptake and lactate production; no changes in systemic cardiometabolic parameters (blood pressure, lipid profile, fasting glucose, insulin, and HOMA-IR); ↓ circulating inflammatory markers (IL-6, IL-5, IL-2 and TNF-α)	- Small sample size - Only male subjects - No measure of physical performance at baseline
Dolopikou et al. (2019)(26)	12 old males (71.5±1 years old) and 12 young males (22.9±1 years old)	500 mg/ day	1 day	↑ NAD+ metabolites in erythrocytes; ↓ F2 isoprostanes in urine by 18%; ↑ isometric peak torque by 8% and fatigue index by 15% in old male	- Small sample size - Only male subjects - No measure of NAD+ metabolites in muscle - No safety data
Martens et al. (2018)(34)	24 subjects, (65±7 years old)	1000 mg/day	6 weeks	No serious adverse effects; ↑ NAD+ metabolites in PBMCs; ↓ systolic blood pressure in individuals with elevated/stage I hypertension; no other significant change of indicators of CV health; no improvement on aerobic exercise capacity or motor function	- Small sample size - No measure of NAD+ metabolites in muscle
Dollerup et al. (2018)(33)	40 (20: NR treated) Caucasian males, insulin-resistant, obese (58±1.6 years old)	2000 mg/day	12 weeks	No serious adverse effects; Vs. Placebo: ↑ NAD+ metabolites in urine; Vs. Baseline: no differences in body composition; not improve insulin sensitivity and other metabolic parameters	- Small sample size - Only white male subjects - Low generalizability

NR: nicotinamide riboside; NAD: nicotinamide adenine dinucleotide; HOMA-IR: homeostatic model assessment of insulin resistance; IL: interleukin; TNF-α: tumor necrosis factor alpha; SIRT: sirtuin; NAMPT: nicotinamide phosphoribosyltransferase; PBMCs: peripheral blood mononuclear cells