Your New Party Trick: NMN Supports Liver Health After Alcohol Intake

From the beer-brewing Sumerians in ancient Mesopotamia to the wine-loving philosophers in Greece and Rome, cultures all over the world have been fermenting grains or fruit to create alcoholic beverages for thousands of years. However, when it comes to modern-day drinking, many people are rightfully confused about whether or not the mind-altering substance is good or bad. On the one hand, research has found that light-to-moderate alcohol consumption reduces the risk of heart disease and mortality. On the other hand, anything more than moderate consumption can quickly become toxic, increasing the risk of obesity, heart and liver disease and more. 

As the primary site for processing and breaking down toxins, the liver is the first organ affected by heavy alcohol consumption, leading to alcoholic liver disease (ALD) over time. Many people don’t realize they are classified as ‘heavy consumers,’ as health organizations define this as more than one alcoholic drink per day for women or more than two for men. However, a significant proportion of American adults — up to two-thirds of us, in fact — enjoy drinking a glass or two to unwind at the end of the day, but may not want the liver dysfunction that comes along with it. This leads researchers and at-home drinkers alike to wonder if there’s a way to still imbibe while preventing this internal damage.

The answer may lie with the compound nicotinamide mononucleotide (NMN), a precursor to the vital coenzyme nicotinamide adenine dinucleotide (NAD+). A crucial component of all cellular and metabolic processes, NAD+ levels are known to decline with age. Low NAD+ levels are also implicated in many, if not all, chronic diseases — including alcoholic liver disease. In a recent study published in Human Genomics, Assiri and colleagues use supplemental NMN to mitigate these low NAD+ levels, and with it, reduce the liver damage that comes with chronic alcohol consumption.

The Vicious Cycle of Alcohol Intake and NAD+ Depletion

Excessive alcohol intake will lead to ALD over time, with the early stages of the disease typically not causing many symptoms yet still producing significant liver damage. This alcohol-induced damage arises from a trio of factors: inflammation, metabolic dysfunction, and oxidative stress — the accumulation of compounds called reactive oxygen species that cause damage to cells, proteins, and DNA. 

In the case of metabolic dysfunction, low NAD+ levels contribute to alcoholic liver disease by disrupting the proper functioning of hepatocytes — the most abundant type of liver cells that are essential for metabolism and detoxification. Additionally, alcohol intake directly depletes NAD+ stores because NAD+ is used as a cofactor in two reactions in the liver to break down ethanol. This alcohol-induced depletion combined with low NAD+ levels then causing further hepatocyte dysfunction causes a vicious cycle of liver injury when consuming alcohol. This led Assiri and colleagues to wonder if replenishing the depleted NAD+ stores could break this cycle and improve liver health in mice who were models of early-stage ALD. 

NMN Every Other Day Keeps the Liver Damage Away

First, the research team looked at two widely-used measures of liver function that are typically found on standard lab panels, the enzymes ALT (alanine aminotransferase) and AST (aspartate aminotransferase). Under normal conditions, ALT and AST are primarily contained within hepatocytes or other cells. Upon liver injury or damage, the cells will spill these enzymes out into the bloodstream, which causes blood plasma ALT and AST levels to rise, indicating liver disease in some capacity. 

In this study, mice who consumed ethanol (alcohol) daily for six weeks had significant increases in ALT and AST, while the mice who also received every-other-day injections of 500 mg/kg of NMN did not see the same elevation (this dose would translate to nearly 1.5 g of NMN daily in an average-sized American of 176 pounds). This mitigation of ALT and AST elevation suggests that NMN plays a protective role in alcohol-induced liver damage. Plus, NMN injections also boosted NAD+ stores in the liver and prevented the alcohol-induced decrease in two essential compounds for metabolic function: pyruvate and alpha-ketoglutarate. These metabolites are vital to the TCA cycle, a series of chemical reactions that produce the primary source of energy for our cells. 

Normalizing Gene Activity With NMN 

In addition to directly impacting liver function, chronic alcohol intake significantly altered gene activity, while NMN treatment mitigated some of these changes. One gene that is largely involved in liver health is Atf3, which encodes for a transcription factor — a protein that helps to turn genes on or off by binding to DNA — that alters liver metabolism. Overexpression of Atf3 occurs in response to stressors (including alcohol) and is detrimental to the liver, as high activity of Atf3 increases ALT and AST levels. 

In this study, the mice that consumed alcohol without receiving NMN had roughly a 40-fold increase in Atf3 activity compared to mice that did not consume alcohol. Although it didn’t completely alleviate the overexpression of Atf3, NMN markedly improved it, as the NMN-injected mice reduced this activity to about 5-fold.

As elevated Atf3 activity is implicated in other liver disorders, including fatty liver and acute liver injury, the research team believes that preventing Atf3 overexpression with NMN may be a crucial mechanism for supporting liver health in ALD cases. As summarized by Assiri and colleagues, “Our findings here demonstrate that the prevention of Atf3 overexpression by NMN is an important mechanism that may support hepatoprotection and will be a focus of follow-up studies.”

Is NMN the Future of Liver-Supported Drinking?

As previous research has found that NMN prevents the abnormal accumulation of scar tissue in the liver called fibrosis, it’s likely that this NAD+ precursor can also mitigate the damaging effects of alcohol on the liver. However, this study only looked at early-stage ALD — it’s unknown if the same benefits would be seen in more advanced stages of alcoholic liver damage. And, this study was only done with mice, so we don’t know for sure if it will benefit humans.

But, for the average adult who drinks just slightly more than the recommended amount of alcohol, boosting liver NAD+ with supplemental NMN may be a beneficial way to bolster liver health once you surpass that second glass. While we’re certainly not recommending binging on alcohol night after night, NMN may be able to provide you with the extra liver support you need on those (hopefully) rare nights you imbibe in a few extra. We’ll cheers to that.

References: 

Assiri MA, Ali HR, Marentette JO, et al. Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease. Hum Genomics. 2019;13(1):65. Published 2019 Dec 10. doi:10.1186/s40246-019-0251-1

Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ. 2011;342:d671. Published 2011 Feb 22. doi:10.1136/bmj.d671