Key Points

• IV NR was well tolerated at doses up to 450 mg/kg

• High doses (600 mg/kg) caused negative effects, including cardiovascular, liver, and kidney damage

Increasing Doses of IV NR Evaluated in Rats 

Researchers administered NR intravenously to rats at doses of 150, 300, 450, and 600 mg/kg over a period of 3.5 weeks. 

They monitored the animals’ organ health, behavior, bloodwork, and survival.

No Harm Seen at Lower Doses

At doses of 150–450 mg/kg:

• Rats maintained normal behavior, organ function, and cardiovascular health

• No harmful changes were seen in the heart, liver, kidneys, or blood tests

• Even at 450 mg/kg, there were no adverse effects on the heart’s nervous system

“Repeated intravenous administration of NR within the dose range of 150-450 mg/kg is characterized by a biocompatibility.“

Toxic Effects at the Highest Dose (600 mg/kg)

At 600 mg/kg, several concerning effects appeared:

• Reduced heart function and exercise tolerance

• Damage to heart, liver, and kidney tissue

• Increased mortality

“The dose increase up to 600 mg/kg leads to marked myocardial, renal, and hepatic dysfunctions.”

Estimated Human Equivalent Dosages

Using standard body surface area scaling:

• 450 mg/kg in rats ≈ 5,080 mg in a 70 kg (150 lb) human

• 600 mg/kg in rats ≈ 6,774 mg in a 70 kg (150 lb) human

The 450 mg/kg dose (equivalent to ~5 g IV NR in humans) appeared safe in rats with no adverse effects, while 600 mg/kg caused harm.

Conclusion

 

The study suggests that intravenous administration of NR is safe at doses up to 450 mg/kg in rats.  

Higher doses (600 mg/kg) may lead to significant adverse side effects.