Table 2.

Effects of NR administration in vivo

Mouse model	Gender	Dose	Duration	Outcome	Ref
Chow-fed or High fat diet-induced obese C57BL/6 mice	male	~400 mg/kg (diet)	12 weeks	Decreased weight gain, improved insulin sensitivity.	(Canto et al., 2012)
Tg2576 mice (Alzheimer’s disease model, C57BL/6 background)	unspecified	~250 mg/kg (diet)	3 months	Slowed cognitive decline.	(Gong et al., 2013)
“Deletor” mice (Twinkle mutant causing mitochondrial myopathy, C57BL/6 background)	male	~400mg/kg (diet)	4 months pre- or post-manifestation	Induced mitochondrial biogenesis and stimulated mitochondrial unfolded protein response	(Khan et al., 2014)
Sco2 knockout E129K knockin mice	unspecified	~400mg/kg (diet	4 weeks	Improved endurance and mitochondrial respiratory capacity in muscle	(Cerutti et al., 2014)
Human Unconventional RBP5 interactor knockin mice (inducible, liver-specific)	unspecifed	~500mg/kg (diet)	9–57 weeks	Prevented DNA damage and tumor development in livers when given early, tumor regression when given late	(Tummala et al., 2014)
4 or 18 month old C57BL/6 wt and Csbm/m mice	male	500 mg/kg (IP)	1 week	Improved the function of mitochondria isolated from cerebellum.	(Scheibye-Knudsen et al., 2014)
3 month old C57BL/6 wild-type or Xpa−/−/Csa−/− (CX) mice	unspecified	500 mg/kg (SC)	14 days	Lowered mitochondrial membrane potential and ROS (Also noted that CX genotype is lethal if mice are weaned to hard chow and NR in the drinking water of mothers failed to rescue.)	(Fang et al., 2014)
129/SvEv mice with cardiac specific deletion of the transferrin receptor (causing heart failure)	unspecified	750 mg/kg (IP)	P5-death (up to 10 days)	Increased survival time, decreased mitochondrial unfolded protein response, enhanced autophagy.	(Xu et al., 2015)
KK/HIJ mice	male	100 mg/kg (osmotic pump)	7 days	Improved glucose homeostasis, increased adiponectin, and lowered hepatic cholesterol.	(Lee et al., 2015)
C57BL/6, Balb/c, CBA mice, C57BL/6 Sirt3 KO	unspecified	1000 mg/kg (IP)	5 days before and/or 14 days after noise injury (twice daily injection)	Protection against transient or permanent noise-induced hearing loss in all wt strains, but not in Sirt3 KO	(Brown et al., 2014)
C57BL/6 wild-type and liver-specific Sirt1 KO fed high fat high sucrose diet, ApoE KO fed high fat high cholesterol diet	male	~400 mg/kg (diet)	2–18 weeks	Prevented or reversed fatty liver and induced the mitochondrial unfolded protein response with diminished effects in Sirt1 KO.	(Gariani et al., 2016)
C57BL/6 fed chow, high fat diet, or high fat diet + streptozotocin	male	3000 ppm in diet	8 weeks	Improved glucose tolerance, reduced weight gain, reduced hepatic steatosis, protected against neuropathy.	(Trammell et al., 2016b)
C57BL/6 young, aged, muscle stem cell-specific Sirt1 KO, mdx on C57BL/10SnJ background	male	400 mg/kg (diet)	6–8 weeks, or 2 years old death	Improved endurance, grip strength, and recovery from cardiotoxin-induced muscle injury in aged mice, induced the mitochondrial unfolded protein response and delayed senescence in stem cells, increased lifespan	(Zhang et al., 2016)
C57BL/6J mice fed HFD	male	200 mg/kg (diet)	4 weeks	Reduced lipid accumulation and fibrosis in liver	(Zhou et al., 2016)
C57BL/6 wt or muscle-specific Nampt KO	male and female	~400 mg/kg (drinking water)	6 weeks	Restored muscle mass, force generation, endurance, and mitochondrial respiratory capacity in Nampt KO.	(Frederick et al., 2016)
C57BL/6 mice, healthy humans	male (mice), not specified (human)	185 mg/kg (gavage), 500 mg/kg (IP), 1000 mg (PO)	Single, 6 days (mice), single, 7 days (human)	Direct incorporation of intact NR into hepatic NAD+ (mice), no detection of NAD+ or precursor metabolites in plasma (human)	(Trammell et al., 2016a)
Sprague-Dawley rats	male and female	5000 mg/kg (gavage), 750~500 0 mg/kg (gavage), 300~300 0 mg/kg (gavage)	Single, 14 days, 90 days	Toxicity profile similar to nicotinamide, affecting liver, kidneys, ovaries, and testes with no adverse effects observed below 1000 mg/kg/day.	(Conze et al., 2016)
Wild-type and mdx C57BL/10SnJ, mdx/utrophin KO	male	400 mg/kg (diet)	8–13 weeks	Improved muscle function and reduced heart pathology	(Ryu et al., 2016)
C57BL/6 wild-type or liver-specific Nampt KO mice	male	400 mg/kg (drinking water)	14 days prior to and 2 days after partial hepatectomy	Improved liver regeneration, reduced hepatic steatosis, reversal of the poor regeneration phenotype in liver specific Nampt KO mice	(Mukherjee et al., 2017)
C57BL/6 wild-type and Atm−/− mice	male	12 mM (drinking water)	14 days	Improved motor coordination, behavior, Purkinje cell number, and dramatically improved lifespan (Atm−/−)	(Fang et al., 2016)
Human Unconventional RBP5 interactor knockin mice (inducible, liver-specific), C57BL/6 mice fed a high fat diet	unspecified	~500mg/ kg (diet)	5 weeks (3–8 weeks of age)	Decreased DNA damage and inflammatory cell infiltration in liver	(Gomes et al., 2016)
Wistar rats	male	300 mg/kg (gavage)	21 days	Non-significant decrease in swimming performance	(Kourtzidis et al., 2016)
C57BL/6NTac wild-type and Nrk1 KO, or Nrk1/2 double KO mice	male	500 mg/kg, 50 mg/kg (IP)	1 hour	Some degradation of NR to NAM detectable in plasma	(Ratajczak et al., 2016)
C57BL/6JRcc mice fed a med/high fat diet	male	5–900 ppm (diet)	30 ppm for 4 weeks, then stratified to test groups for 15 weeks	Improved metabolic flexibility.	(Shi et al., 2017)
Sprague-Dawley rats injected with paclitaxel or vehicle	female	200 mg/kg (gavage)	7 days prior to and 24 days post-paclitaxel, or 21 days beginning 14 days post-paclitaxel	Prevention or reversal of paclitaxel-induced hypersensitivity to pain, no significant effect on basal locomotor activity (rotarod or open field)	(Hamity et al., 2017)
ICR wt mice fed a high fat diet for 18 weeks	male	300 mg/kg (gavage)	2 weeks	Reduced hepatic ER stress induced by the high fat diet	(Wang et al., 2017)

Abbreviations: IP, intraperitoneal; SC. Subcutaneous; PO, per oral.