Alcohol-Related Liver Disease Linked to NAD Decline

In the first study of its kind on human tissue, researchers have identified a link between alcohol-related liver disease and declines in nicotinamide adenine dinucleotide (NAD), an oxidizing agent found in all living cells and is central to metabolism. NAD levels have been shown to increase through supplementation with nicotinamide riboside, a precursor to NAD.
 
The study found that, in liver samples of patients with alcohol-related liver disease, lowered liver function correlated with a decline in NAD levels.
 
The study, published in Hepatology Communications by a collaborative team from the University of Iowa and University of Birmingham, is the first to evaluate NAD metabolome in human blood samples. The research demonstrated that alcohol-related liver disease (ArLD) is characterized by depressed levels of NAD-related mollecules including NAD, as well as depressed levels of intracellular nicotinamide riboside, which is protective in rodent models of liver disease.
 
“Our goal of identifying the human conditions that can be treated or prevented by nicotinamide riboside supplementation depends on identifying which populations have disturbed NAD systems,” lead investigator Dr. Charles Brenner, head of biochemistry at the Univeristy of Iowa and chief scientific advisor to ChromaDex, said. ChromaDex is a supplier of the patented NR ingredient Niagen, also sold directly to consumers as Tru Niagen.
 
The new study assessed the NAD metabolome in transplant and tissue resections from 72 patients with either ArLD or four other types of conditions. Analysis of the liver tissue from 43 ArLD patients showed marked depletion of AND and its precursors. Depressed NAD levels correlated with low markers of liver function, which were determined using standard liver function tests and histologic presence of steatohepatitis, suggesting that NAD status has important human health consequences.
 
The functional consequences of depressed NAD concentration, researchers said, included a slower fuel oxidation and a limiting of antibacterial defenses in disease states, both of which exacerbate and perpetuate liver injuries. Due to the fact that the ArLD patients who received transplants or resections were abstinent for six months, this research points to the fact that these changes will continue to persist along with the already-existent liver damage.
 
“In summary, these are the first data that describe the NAD+ metabolome in human liver,” the researchers concluded. “The data indicate that two agents, NA and NR, which are protective in rodent models of liver disease, are depressed in ArLD and that the NAD+ metabolome is depressed in ArLD in ways that correlate with functional impairment of defense against infection. In combination with human safety and preclinical efficacy data of NA and NR, these data provide rationale for the investigation of vitamin B3 supplementation in ArLD.