Low Level Intermittent Alcohol Use- Safe or Not Safe – More Gray than Black and White

If you are confused by the reporting on alcohol consumption and health, you’re not alone. There has been a continuous stream of conflicting and contradictory headlines for those paying attention over the years.

For example:

 Drinking alcohol in moderation may benefit heart health, study finds – TODAY, 2023

Light And Moderate Drinking Could Improve Long-Term Heart Health, Study Finds—Here’s Why – FORBES, 2023

Moderate Drinking Provides No Health Benefits, Study Finds – HEALTH, 2023

No level of alcohol consumption is safe for our health – WHO, 2023 

Hmm. One apparent reason for the conflicting data is that epidemiological studies that rely on self-reporting can be biased and have errors. Another factor to consider—for reasons we will present in this blog post—is that it is not a binary question with a simple answer. Instead, it may be that moderate alcohol consumption benefits some individuals and is detrimental to others. 

One way to address bias and errors in reporting is through animal studies. Animals, unlike humans, can be isolated, and everything given to them can be controlled; this fact scrubs clean all the possible confounders that enter human studies. So, what happens when experimental animal models are given low-dose ethanol? The results are typically positive, but they depend on the dose.

Study One

For example, one study substituted drinking water with 3.5% ethanol-water in a group of mice and compared the imbibing to a sober control group. The alcohol-drinking mice "showed improved thermogenic activity, physical performance, and mitochondrial function, as well as resistance against the high-fat diet-induced obesity with elevated insulin sensitivity and subdued inflammation," compared to the control group. Furthermore, the ethanol-dosed mice demonstrated a 4.42% increase in median lifespan.(1) 

Another study using a mouse model with a gene defect for accelerated aging found significant differences between 1% ethanol and 2% ethanol in drinking water. Some negatives were found in the 2% doses, whereas positives were found in the 1% dose.(2) A 1% ethanol dose in our daily water would equate to 1.2 to 1.6 drinks per day in  a normal person.

Study Two

In another fascinating study, researchers at UCLA were accidentally conscripted into research on ethanol.(3) They were studying the effects of cholesterol on C. elegans (a microscopic worm). The cholesterol was dissolved in a tiny amount of ethanol that acted as a solvent. What they discovered was pure luck. “The scientists fed the worms cholesterol, and the worms lived longer, apparently due to the cholesterol. They had dissolved the cholesterol in ethanol, often used as a solvent, which they diluted 1,000-fold. ‘It's just a solvent, but it turns out the solvent was having the longevity effect,’ said Steven Clarke, a UCLA professor of chemistry and biochemistry and the study's senior author.(4) ‘The cholesterol did nothing. We found that not only does ethanol work at a 1-to-1,000 dilution, but it also works at a 1-to 20,000 dilution. That tiny bit shouldn't have made any difference, but it can be beneficial.’ The researchers discovered that cholesterol had zero impact on the lifespan of C. elegans, but the tiny amount of ethanol acting as a solvent had a massive impact, doubling the tiny worm’s lifespan.” “This finding floored us -- it's shocking,” said Clarke.

Biological Phenomenon Hormesis

If low-dose ethanol consumption typically has a positive effect on animals, what are we to make of all of the contradictory data on the human consumption of alcohol? The confusing data may be due to the biological phenomenon known as hormesis. We have visited hormesis in previous blogs. Hormesis is a seemingly contradictory biological phenomenon, yet it makes perfect sense in light of evolution. Hormesis is the imparting of healthy adaptation to biological stressors. Some of the stressors that have been shown to induce hormesis are things that appear on the surface to have no business being “good” for us, like radiation, cold exposure, various toxins, and starvation. Hormesis almost always exhibits a U-shaped curve, meaning there is an optimal dose of the stressor where there is the most beneficial impact on health – too low of a dose equals no effect, and too high of a dose a negative effect. Even exercise falls within a U-shaped curve. No exercise is well-established as harmful to our health, and many studies show that too much exercise can negate the beneficial effects of the optimal amount of exercise.(5)

Because hormesis comes in many forms, it’s easy to imagine each of us has a hormetic bucket that results in optimal health when filled to the right level. Yet most studies on human health fail to consider this. (See this article about how hormesis may explain the endlessly contradicting data in dietary studies.) Like dietary studies, most studies on ethanol consumption don't or cannot consider other hormetic variables that may result in dramatically different results between individuals. One person might not exercise or be exposed to other hormetic stressors; therefore, a dose of ethanol may offer a benefit. Another person may already have their hormetic bucket filled to the optimal level, and the addition of alcohol tips them over into a negative health consequence. This model would explain the contradicting headlines that get reported.

One mouse study appeared to support this hormetic model of ethanol consumption. The study looked at the effect of ethanol on gut health in mice. Groups of young and old mice were given ethanol in drinking water, representing a moderate dose a few days a week for 8 weeks. "Interestingly, moderate ethanol exposure in young animals led to gut protective transcriptional changes in the ileum, while this protective response was blunted in aged mice. Finally, moderate ethanol exposure in aged mice also resulted in marked inflammatory changes in the liver."(6)

This would make sense; a stressor induces a hormetic effect in young mice, but in older mice with a much smaller hormetic bucket, ethanol becomes negative. Like many things in biology, the answer to a single question: is moderate alcohol consumption good or bad? – is not a straightforward yes or no – it is maddingly nuanced and depends on the individual’s unique lifestyle.

Socialization

One other factor to consider is socialization. For some, alcohol is often a part of social gatherings. As readers of this blog know, social contact is possibly the most significant determinant of health. Conversely, loneliness has the most detrimental effect on our health compared to all the other lifestyle factors studied, including smoking and being overweight.

Of course, alcohol, for some people, can be a slippery slope that should be avoided if overconsumption becomes a habit. Still, for others, the social impact of mild to moderate alcohol consumption may be a significant health benefit. If one does choose to imbibe, selecting the lowest carb and cleanest version of the drink and mixer is always prudent.  Timing the intake to reduce the disruption to sleep cycles while supporting the social purpose should always be kept in mind as well. 

Make the responsible choice for yourself and be your own best doctor.

Chuck

Meakin Metabolic Care - Meakin Metabolic Care

Life and Health Coach | Charlotte NC | Coach It Forward Chuck 

Disclaimer: This information is not meant as direct medical advice. Readers should always review options with their local medical team. This is the sole opinion of Dr. Meakin based on a literature review at the time of the blog and may change as new evidence evolves.

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References

1. Diao Y, Nie J, Tan P, Zhao Y, Zhao T, Tu J, Ji H, Cao Y, Wu Z, Liang H, Huang H, Li Y, Gao X, Zhou L. Long-term low-dose ethanol intake improves healthspan and resists high-fat diet-induced obesity in mice. Aging (Albany NY). 2020 Jul 8;12(13):13128-13146. doi: 10.18632/aging.103401. Epub 2020 Jul 8. PMID: 32639947; PMCID: PMC7377878.

2. Kimoto A, Izu H, Fu C, Suidasari S, Kato N. Effects of low dose of ethanol on the senescence score, brain function and gene expression in senescence-accelerated mice 8 (SAMP8). Exp Ther Med. 2017 Aug;14(2):1433-1440. doi: 10.3892/etm.2017.4633. Epub 2017 Jun 20. PMID: 28810607; PMCID: PMC5525595.

3. Castro PV, Khare S, Young BD, Clarke SG. Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae. PLoS One. 2012;7(1):e29984. doi: 10.1371/journal.pone.0029984. Epub 2012 Jan 18. PMID: 22279556; PMCID: PMC3261173.

4. https://www.news24.com/life/archive/tiny-amounts-of-alcohol-extend-a-worms-life-20120721

5. Kankaanpää A, Tolvanen A, Joensuu L, Waller K, Heikkinen A, Kaprio J, Ollikainen M, Sillanpää E. The associations of long-term physical activity in adulthood with later biological ageing and all-cause mortality - a prospective twin study. medRxiv [Preprint]. 2023 Jun 5:2023.06.02.23290916. doi: 10.1101/2023.06.02.23290916. PMID: 37333101; PMCID: PMC10274991.

6. McMahan RH, Najarro KM, Mullen JE, Paul MT, Orlicky DJ, Hulsebus HJ, Kovacs EJ. A novel murine model of multi-day moderate ethanol exposure reveals increased intestinal dysfunction and liver inflammation with age. Immun Ageing. 2021 Sep 23;18(1):37. doi: 10.1186/s12979-021-00247-8. Erratum in: Immun Ageing. 2021 Oct 21;18(1):39. PMID: 34556145; PMCID: PMC8459518.