Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD+ without impacting respiratory capacity or insulin sensitivity

Balancing NAD+ deficits with nicotinamide riboside: therapeutic possibilities and limitations

“…• NR had no impact on exercise performance or muscle mitochondrial content in mice fed a regular diet [ 152 , 215 ]…”

“…MUSCLE PERFORMANCE • NR had no impact on exercise performance or muscle mitochondrial content in mice fed a regular diet [152,215] • No alterations in the skeletal muscle acetyl-proteome after NR treatment [207] • NR prevented the decline in muscle mitochondrial function triggered by chronic high-fat feeding [152] • Acute (2 h) or short-term (7 days) NR supplementation did not influence muscle performance or response to exercise in healthy young individuals [216,217] • No effect of NR supplementation on muscle mitochondrial content and respiratory capacity in overweight or obese pre-diabetic individuals [218,210] AGE-RELATED DECLINE (I): CARDIOVASCULAR FUNCTION • NR improved cardiac NAD + levels, cardiac function and premature death in a mouse model of altered LMNA function [219] • NR attenuated the development of heart failure in models of dilated cardiomyopathy or transverse aorta constriction, as well as in response to pressure overload. [94,220] • NR reduced the levels of circulating pro-inflammatory cytokines in patients with Stage D heart failure [221] • No change in cardiovascular parameters, but reduced systemic inflammation in elderly [222] • NR supplementation reduced some parameters linked to hypertension [205] AGE-RELATED DECLINE (II):…”

Circadian cardiac NAD+ metabolism, from transcriptional regulation to healthy aging

“…Though potentially difficult or expensive to perform injudiciously, labeling studies for NAD + synthesis have been successfully executed previously ( 57 ), and genetic tools have been made to successfully distinguish cytosolic and mitochondrial measurements of NAD + and NADH in isolated cardiomyocytes ( 70 ). In the case of NR, there is a significant clinical appeal in its oral availability ( 71 ), but investigations into muscle and heart NR supplementation find that much of the orally given NR is absorbed by the liver ( 36 , 72 , 73 ). Intraperitoneal supplementation with NR in a nondisease state reduced Nmrk2 expression ( 72 ), which may explain why some heart studies were unable to elevate NAD + levels with NR in control mice ( 69 ).…”

“…In the case of NR, there is a significant clinical appeal in its oral availability ( 71 ), but investigations into muscle and heart NR supplementation find that much of the orally given NR is absorbed by the liver ( 36 , 72 , 73 ). Intraperitoneal supplementation with NR in a nondisease state reduced Nmrk2 expression ( 72 ), which may explain why some heart studies were unable to elevate NAD + levels with NR in control mice ( 69 ). NMN is most often tried in mouse models with intraperitoneal injections, but toxicity quantities have not been evaluated sufficiently in humans ( 65 , 68 ).…”

Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women

“…NR supplementation also prevented weight gain in mice fed high-fat diet, as well as increased insulin sensitivity and mitochondrial mass in skeletal muscle 36 . Furthermore, Damgaard et al showed that intravenous injection of NR increased NAD+ in mouse skeletal muscle without affecting respiratory capacity or insulin sensitivity 37 . The administration of NMN and NR to rodents, Caenorhabditis elegans (nematodes), and Drosophila melanogaster (fruit flies) has been shown to prolong lifespan and alleviate age-related physiological decline 38 – 40 .…”