Long Term Low Dose Ethanol Intake Modestly Extends Life in Mice

As of the past few years, the long-standing debate over whether moderate alcohol intake has a protective effect on health had appeared to resolve to the conclusion that the observed epidemiology is explained by socioeconomic factors, not by the metabolic effects of molecules such as polyphenols present in wine or other alcoholic drinks. People who engage in more modest alcohol consumption tend to be in the wealthier sections of society, and thus are more health conscious, undertake lifestyle choices, and make better use of available medical technologies.

In that context, today's open access paper is quite interesting. The authors report on a study in which a 4.4% extension of mean lifespan and various improvements in metabolism take place in mice that are given drinking water that is 3.5% ethanol, that intervention starting at 8 weeks of age. The researchers suggest that this might be mediated by pathways involving AMPK and mitochondrial function, and note that there is a comparatively lack of research into alcohol intake at this low, sustained level. It will be interesting to see how this line of inquiry develops in the years ahead, although I'd be the first to say that the effect size here is far too small to be of more than academic interest.

Long-term low-dose ethanol intake improves healthspan and resists high-fat diet-induced obesity in mice

Previous studies on the protection of alcoholic beverages have been primarily focused on the polyphenols such as resveratrol, procyanidins and other substances like catechin and tannin. Ironically, the most important common component of all alcoholic beverages, alcohol or ethanol, has received much less attention. In this study, we use ethanol, the common substance in all kinds of alcoholic beverages, as a single variable to explore its effects in vivo. Our data showed that the long-term 3.5% ethanol substitution for drinking water had beneficial effects in mice, the daily performance of ethanol-fed mice was enhanced, the athletic ability and healthspan of ethanol-fed mice drastically improved. Furthermore, the ethanol-fed mice showed the resistance to high-fat diet (HFD). When supplemented with 3.5% ethanol, the HFD mice showed reduced multiple organ pathogenicity, increased insulin sensitivity, and decreased NF-kB activation and inflammatory cytokines. These changes caused by ethanol are astonishing and impressive.

It has been well accepted that acute and chronic excessive alcohol exposure is conducive to tissue injury. However, one should be mindful that the injuries caused by the excessive use of alcohol are dose-dependent. In our study, the long term 3.5% ethanol-fed mice did not show the common negative effects of alcohol. At this dose, we did not observe any pathological structural changes in the liver, the heart, or the kidneys; neither did we detect any impairments of learning, memory, and cognition by the water maze.

One of the pathophysiological mechanisms induced by alcohol abuse has been identified as mitochondrial dysfunction. On the other hand, the mitochondrial volume was associated with high levels of physical activity. The improved mitochondrial function of long-term low-dose ethanol-intake (LLE) mice may be due to their high level of daily physical activity and enhancement of athletic ability of LLE mice. In our experiments, we observed that the mitochondrial density in the liver and the skeletal muscles of the ethanol-fed group increased, and the morphology became stronger with more cristae, indicating improved mitochondrial function under the moderate ethanol feeding.

AMPK induces mitochondrial biogenesis and has emerging roles in the regulation of both mitochondrial metabolism and dynamics. Phosphorylation activity of AMPK, necessary for mitochondrial biogenesis via SIRT1 and PGC1a, was increased in the liver of the LLE mice. Considering the activation of AMPK by moderate ethanol intake, it seems reasonable to entertain the hypothesis that the rapid acetate metabolism following the ingestion of ethanol generates sufficient AMP to transiently activate AMPK, which in turn induces the synthesis of certain long-lived proteins that act to boost insulin sensitivity and possibly aid the efficiency of fat oxidation as well.

Comments

I read somewhere that 1 gram ethanol get the brain to age 1 week. Be careful Aubrey. We have to take care of him.

Posted by: Gekki at July 29th, 2020 4:50 PM

If ethanol were discovered today it would be illegal. Its neurotoxic. Therefore Im sceptical. I think theres far more evidence for ethanol to be unhealthy. Does readers agree/disagree? I don't think we should take up drinking because of this.

Posted by: thomsa.a at July 30th, 2020 5:07 AM

Based on results to date, my take on EtOH is that (1) it increases cancer risk proportional to dose (i.e., there is no safe dose), and (2) it's effect on all-cause mortality is U-shaped and modest, with minimum risk near 1/2 "drink" per day (about 7g EtOH/d). Interestingly, the discussed study, by my estimate, is exposing the mice to about 3 drinks per day, on a human equivalent basis (i.e., after allometric scaling), so not sure what to make of that. Anyway, one is probably better off finding other ways to decrease all-cause mortality than adding to cancer risk with EtOH.

Posted by: dtkamp at July 30th, 2020 10:20 AM

@dtkamp: I agree. We should focus on find ways to mimic the benefits.

Posted by: Norse at July 30th, 2020 12:09 PM

"The authors report on a study in which a 4.4% extension of mean lifespan and various improvements in metabolism take place in mice that are given drinking water that is 3.5% ethanol," -Read beer

"In wine there is wisdom, in beer there is Freedom, in water there is bacteria." I image for lab rats confined to cages, the taste of freedom might make life worth living 4.4% longer.

Posted by: Thomas Schaefer at July 31st, 2020 9:56 PM

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.