Metabolism

Binge Drinking Causes Liver Damage by Reducing Cellular Levels of NAD+

Excessive alcohol consumption and binge drinking reduce levels of free nicotinamide adenine dinucleotide (NAD+) critical to cellular health and energy production, resulting in liver and organ damage.

(Victoria Denisova | iStock)
By Bennett M. Sherman

Alcohol consumption can provide a welcome reprieve from the hassles of every-day life but can lead to binge drinking and excessive alcohol consumption. Over time, excessive alcohol use results in the development of chronic diseases and other serious problems.

UCLA scientist and pathologist Dr. Samuel French published a review on the effects of chronic alcohol binging on cellular health. In his review, Dr. French specifically examined how binge drinking injures the liver and other organs by diminishing the cellular levels of a molecule called nicotinamide adenine dinucleotide (NAD+).

NAD+ is a coenzyme—a compound necessary for the functioning of an enzyme—in numerous metabolic reactions critical for healthy aging and lifespan, such as the generation of cellular energy (i.e., reduction-oxidation reactions). NAD+ also binds enzymes called sirtuins that promote cellular health through DNA repair—a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome.

NAD+ molecule

Dr. French’s review highlights studies showing that high blood alcohol levels result in the conversion of NAD+ to a form called NADH that inhibits its functionality as a coenzyme. Also, with high blood alcohol levels, sirtuin enzymes become more abundant in cells. However, with NAD+ not available to facilitate sirtuin function, there is an increased quantity of protein modifications in liver cells that induce an inflammatory response and, ultimately, cause alcoholic fatty liver disease. What’s more, all enzymatic activities dependent on NAD+ shut down, leading to reduced lifespan and healthspan.

The review also covers studies showing that reduced NAD+ availability alters the body’s natural 24-hour clock (i.e., circadian rhythm), which can adversely affect metabolism and energy generation in the cell’s powerhouse—the mitochondria. Reduced NAD+ concentrations affect the body’s circadian rhythm by disrupting sirtuin activity that regulates proteins critical to maintaining the body’s clock.

“NAD is a linchpin of energy metabolism and its diminishing level with age has been implicated in mitochondrial deterioration during aging,” concluded Dr. French. Chronic alcohol use and binge drinking can add to these effects by reducing NAD+ levels and contributing to the dysfunction of sirtuins and, ultimately, mitochondria. The review suggests that increasing levels of NAD+ can elevate sirtuin activity to promote beneficial cellular effects, such as the generation of new mitochondria. Along these lines, research has shown that NAD+ boosters like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) can prevent mitochondrial deterioration.

Source

French SW. Chronic alcohol binging injures the liver and other organs by reducing NAD⁺ levels required for sirtuin’s deacetylase activity. Exp Mol Pathol. 2016 Apr;100(2):303-6. doi: 10.1016/j.yexmp.2016.02.004. Epub 2016 Feb 16. PMID: 26896648.

References

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