Alcohol may injure the liver, other organs by reducing NAD+ pool required for sirtuin activity

Using existing research and experimental results a scientist pieces a mechanism together how alcohol injures the liver and other organs during chronic and binge alcohol drinking.

Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase. The consequences of alcohol metabolism include oxygen deficits in the liver, formation of highly reactive oxygen-containing molecules that can damage other cell components and changes in the level and ratio of NADH to NAD+.

In more detail the alcohol dehydrogenases comprise a group of several isozymes that catalyse the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, and also can catalyse the reverse reaction. In mammals this is a redox (reduction/oxidation) reaction involving the coenzyme nicotinamide adenine dinucleotide (NAD+). The researcher noted that NAD+ levels are markedly reduced when blood alcohol levels are high during binge drinking. This likely causes liver injury to occur because the enzymes that require NAD+ as a cofactor such as the sirtuin de-acetylases cannot perform their function. This stalls cell processes which could prevent and repair organ injury such as fatty liver in response to alcohol abuse. Because alcohol dehydrogenase is present in every visceral organ in the body it is plausible that NAD+ levels in all of these organs are reduced during binge drinking and similarly impact organ health.

While not mentioned in the acticle nicotinamide riboside is known to boost NAD+ levels and it could be speculated that supplementation may hence be beneficial on a night out. Better in any case is of course to moderate alcohol consumption.

You can find the researchers manuscript here.

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