A team of researchers from King Saud University, Saudi Arabia; the University of Colorado Anschutz; and Duke University have found previously unreported cellular mechanisms in the liver that nicotinamide mononucleotide (NMN) supplementation affected in mice with early stage chronic alcohol consumption (mouse model of chronic alcohol consumption).  Their study also provided evidence that nicotinamide mononucleotide (NMN) administration may have limited liver damage in these mice.

A paper published in Human Genomics on December 10, 2019 described how the researchers used a nicotinamide adenine dinucleotide (NAD+) boosting supplement, nicotinamide mononucleotide (NMN), to uncover effects of nicotinamide mononucleotide (NMN) consumption in alcoholic liver disease development (pathogenesis) in mice.  The team of scientists embarked on this study, because chronic alcohol consumption has contributed significantly to liver disease worldwide. The resulting alcoholic liver disease entailed inflammation and dysregulation of metabolism.

The researchers used measurable indicators of a biological state (biomarkers) called alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to determine liver damage in mice given saline (control group) and mice given ethanol (experimental group).  As expected, the scientists found significantly higher biomarker levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice treated with ethanol (alcohol), which indicated liver damage. The scientists performed an experiment where they gave a group of mice saline and nicotinamide mononucleotide (no alcohol plus NMN) and another group of mice nicotinamide mononucleotide and ethanol (alcohol plus NMN).  They found no difference in biomarker levels for liver damage between these groups. These findings suggested that administering nicotinamide adenine dinucleotide (NAD+)-boosting nicotinamide mononucleotide (NMN) limited liver damage in mice that consumed alcohol.

Image from Assiri et al. (2019)

The researchers also wanted to determine if alcohol toxicity decreased levels of available nicotinamide adenine dinucleotide (NAD+) in the liver with nicotinamide mononucleotide (NMN) administration.  Previous studies have shown that alcohol toxicity associated with alcoholic liver disease (ALD) facilitated diminished levels of nicotinamide adenine dinucleotide (NAD+). Their results provided evidence in this mouse model of alcoholic liver disease (ALD) showing injection of nicotinamide mononucleotide (NMN) successfully increased levels of nicotinamide adenine dinucleotide (NAD+) with alcohol consumption.

Image from Assiri et al. (2019)

The scientists went on to measure the effects of nicotinamide mononucleotide (NMN) administration on metabolism in the mouse model of alcoholic liver disease.  Previous studies showed that chronic alcohol consumption resulted in dysregulated expression of genes involved in liver metabolism. The studies showed a protein (transcription factor) involved in regulating expression of metabolic genes, Atf3, had overexpressed levels in liver damage.  Alcohol consumption induced overexpression of this protein (Atf3). Such overexpression of this protein (Atf3) inhibited the body’s production of sugars (gluconeogenesis). This study provided evidence nicotinamide mononucleotide (NMN) administration mitigated these effects in early stages of chronic alcohol consumption in mice.

The evidence that this study provided showing nicotinamide mononucleotide (NMN) administration in mouse models of alcoholic liver disease (ALD) limited liver damage as measured with biomarkers of liver damage may translate to humans.  Scientists often have made discoveries using mouse models before applying similar studies in humans. Thus, the possibility remains that the nicotinamide adenine dinucleotide (NAD+) booster, nicotinamide mononucleotide (NMN), may act as a therapeutic strategy for intervention in alcoholic liver disease. 

Evidence supporting use of the nicotinamide adenine dinucleotide (NAD+) booster, nicotinamide mononucleotide (NMN), for intervention in alcoholic liver disease came from this study in mice, which showed nicotinamide mononucleotide (NMN) administration limited liver damage and maintained nicotinamide adenine dinucleotide (NAD+) levels with alcohol consumption.  Furthermore, nicotinamide mononucleotide (NMN) may have alleviated metabolic dysfunction associated with chronic alcohol consumption. Further research on this topic was necessary before scientists could make therapeutic recommendations.

Authors of this study included Mohammed A. Assiri of King Saud University, Riyadh, Saudi Arabia; Hadi R. Ali, John O. Marentette, Youngho Yun, Laura M. Saba, Peter S. Harris, and Kristofer S. Fritz of University of Colorado Anschutz, Aurora, Colorado; Juan Liu and Matthew D. Hirschey of Duke University, Durham, North Carolina.

The work and researchers of this study were supported with grants from the National Institutes of Health.