Part 6 Hormesis - Alcohol
Hormesis (exposure to stress to create a benefit) is proving to be an useful important tool in our health arsenal. From cold exposure to psychedelic micro-dosing and much more in between, the field has much potential. Part 6 in our 7 part series addresses one of the most commonly indulged modes of hormesis. Unfortunately, the vast majority tend to overdo it, most of the time.
Read a complete introduction to Hormesis in the first part of our Hormesis series.Hormesis - Alcohol
Every year the media seems to shout out to the world a new “definitive truth” regarding alcohol. Either it is “good for us” or “unequivocally bad for us.” One of the issues with the media in general regardless, whether it is health or science reporting or politics, is that there is a need to create attention-grabbing headlines. Such headlines and accompanying slant to deliver something close to the headline veers content away from accuracy.
Compounded by most journalists lacking a background or understanding of the science they are covering and a tendency to either accept without scrutiny or reject to show the opposite stance of their competitors, the messaging ends up being extreme and bipolar.
Messaging on alcohol tends to fit into extremes because of its popularity. Most adults partake in the odd drink and it stands to reason that most are interested in the long-term benefits, or detriments, a favored activity has on their health.
As I’ve specifically and repeatedly written throughout the first five parts of this series, no form of hormesis is safe or beneficial in all amounts or intensities. Concerning this series, at least, this is most true with alcohol.
There is a very fine line between beneficial and harmful when it comes to alcohol, and we do not yet know where that line definitively lies. What further complicates the issue is like other forms of hormesis, an individual’s tolerance may play a role. While we may be able to determine the average consumptions of specific mg or g/kg levels of ethanol consumption, individual benefits may vary.
From a strictly cautious health standpoint, abstinence or well below the ideal tolerance is likely the smartest route. Personally, I thoroughly enjoy a full-bodied glass of red wine and on top of my personal enjoyment, I tend to write better, think more creatively, and do much of my best work after a glass or two.
Of course, if that glass or two turns into a bottle or two, my writing becomes poor in quality and high in errors, and I tend to send ill-advised e-mails. Further negating the benefit, the physiological stress of the hangover far outweighs the momentary delight of intoxication, at least from my perspective in the last several years.
From an anecdotal standpoint, blue zone populations in the world studied for their unusual longevity, partake in moderate daily alcohol consumption, especially wine. It was not too long ago that journalists were shouting that we have found the “why” in red wines longevity activation, attributing it to resveratrol. I will dive into that topic in this article, but as a preface, there is much more to the story than just one molecule found only in one type of alcohol.
Ethanol: Poison or Therapy?
I’m certainly not the first to suggest alcohol is a form of hormesis from which we can determine therapeutic dosages with optimal levels (between one to three drinks a day) accounting for lowered risks of dementia, cardiovascular disease,1 osteoporosis, and mortality, with higher intake, sharply increasing risks.2, 3, 4, 5
However, a combination of oversimplified and incorrect media positions, as well as a steep cliff in benefits descending into harm, confuses many readers. Suggesting alcohol can be good for you is an intellectual hurdle for many to grasp, often due to personal experiences regarding the negatives of overconsumption. Like other forms of hormesis, ethanol can be both a poison and a therapy or more simply, the dose makes the poison.
Ethanol has been noted to affect a plethora of animal and human behaviors in a two-phase, or biphasic, dose-dependent manner with low doses being stimulatory and higher doses being inhibitory.6 This has been observed in studies on anxiety and depression, with low levels improving conditions and high intake aggravating proper mood function.7
This can be quite problematic, as those suffering from depressive disorders are more likely to drink to excess, exacerbating their condition.8 Since alcohol also tends to alter “the reward center” of our brain, increasing our proclivity to gamble and take chances,9 the cumulative results can be devastating for those who suffer from alcoholism.
Alcohol tends to either promote a beneficial outcome or drive towards a “disease” state when overdone, similarly to other forms of hormesis. Similarly to exercise where moderate training in men who had previously been sedentary dramatically improves testosterone10, 11 and chronic overtraining significantly decreases testosterone,12 mild to moderate alcohol intake has shown to increase testosterone in both men13 and male rats,14, 15 while chronic consumptions decreases it16, 17 along with many other negative impacts.
Alcohol has been researched heavily in both cardiovascular disease and prevention. Some of the benefits of moderate alcohol intake could very well be from the release of heat shock proteins18 as well as endothelial nitric oxide synthase (eNOS) production.19 While clinical data studying alcohol for cardiovascular function is non-existent (due to ethical concerns), observational studies, as well as research looking into modes of action and rodent studies, are able to ascertain both benefits and harms.20
In covering other forms of hormesis, we know that autophagy is critical and activated by at least caloric restriction, fasting, and exercise. When it comes to mice, ethanol has also shown to induce autophagy, although the role of FOXO3a plays a critical role in expressing this outcome with overexpression of a dominant form inhibiting autophagy. Pharmacologically-activated intermittent or acute stress promotes autophagy in the liver and helps to attenuate alcohol caused liver damage, while inhibition exacerbates it.21
mTOR signaling may also play a role in alcohol and autophagy as well as in overall mortality and life extension, as it has been noted that mild to moderate alcohol consumption inhibits mTOR.22, 23, 24 A great review of alcohol and aging, covering ethanol’s role with mTOR and FOXO3a can be found here.25
Ethanol has shown to promote neurogenesis in the hippocampus of rodents consuming moderate amounts of alcohol without triggering apoptosis,26 the process in which new neurons are created in our brain. As most “know,” overconsumption of alcohol kills brain cells.
In reality, overconsumption of ethanol kills the neuronal stem cells needed for neurogenesis.27 It also damages dendrites, the end of our neurons needed for “proper communication” through our brain, specifically in regions that moderate “reward”.28 Furthermore, a large Australian cohort study of 7,485 participants found light or moderate drinkers had superior cognitive function to those abstaining from alcohol altogether or those drinking in excess to hazardous levels.29
The proper function of the glymphatic system, our internal system that deals with junk removal in our central nervous system (CNS), is critical in both the prevention and development of various neurological and CNS disease.30
In a recent study, it was demonstrated that moderate amounts of alcohol activated the murine glymphatic system, which would hypothetically create a protective effect against many diseases, and completely deactivated the glymphatic system with heavy consumption.31 The differences were quite significant and complete suppression was only seen at three times the levels of activation.
When those two glasses of wine turns into six, the therapy turns to poison. When a dose goes from therapeutic to deleterious in a very small change, it is known as having a steep “J” or “reverse J” curve, due to the graphical resemblance of a J. Alcohol’s looks something like this in terms of mortality:
Regarding the glymphatic system, the J is “reversed”, with small amounts “activating” and larger amounts “deactivating”
Alcohol and Sleep
The relationship between alcohol and sleep is a bit more complicated. While alcohol in moderate amounts may improve sleep duration, it decreases REM sleep and total sleep quality.32 Even the use of alcohol for insomniacs has conflicting data, with some parameters improving and others, such as REM, decreasing.33
Anecdotally, I have found that if I drink my wine late at night after dinner and right before bed, even two to three glasses leave me hungover. If I drink my wine before that or during dinner in the early evening and then go for a walk or am otherwise active, I feel no ill consequences.
Lack of Sleep Deactivates the Glymphatic System
While alcohol in moderate dosages may activate the murine glymphatic system, for humans, this may end up being more complicated. Lack of sleep, or specifically deep REM sleep, deactivates the glymphatic system.34 Since even low use of ethanol before bed serves to impact REM sleep, therapeutic drinking should be avoided right before bed.
It has already been established that alcohol is biphasic and perhaps the benefits to the glymphatic system can be achieved while mitigating disruptions to sleep if a glass or two is enjoyed in the early evening. Suggesting “day drinking” may be a tad risqué, but I suspect much of a gap is not necessary so long as no noticeable intoxicating effects are observed (and if you’re intoxicated, you likely swept down the J curve into damage and harm).
As discussed in part II of our series on AGEs, resveratrol is one of the most hyped and marketed putative anti-aging supplements to emerge in the last few decades and has been studied for its implications in life span, cancer, metabolism, cardiovascular issues, and neurodegenerative issues.
We discussed its seeming ability at reducing AGEs, noting a recent study found that resveratrol inhibits AGE-induced proliferation and collagen synthesis activity.35 Furthermore, resveratrol shows positive results in studies pertaining to diabetes, such as its effect in type II diabetic rats.36
While the benefits of red wine were attributed to resveratrol for a time, the actual dosage obtained through red wine is quite insignificant, at a fraction of a milligram per glass.37 Perhaps more importantly, it has been found that the combination of resveratrol and ethanol worked synergistically in inducing autophagy as resveratrol decreases FOXO3a acetylation, while alcohol inhibits mTOR activity and increases NADH/NAD+ ratios.38
Further evidence remains lacking, but since red wine is my favored beverage, I will jump all over this, actively acknowledging my selfish confirmation bias.
Hormeses - Alcohol Conclusion
Alcohol can likely exert some biological benefits, so long as it is used therapeutically in moderation. For most, attempting to do so will lead to harmful results.
Personally, I love a glass of wine or two whether it be while reading, writing, listening to music, or over dinner with my spouse and/ or friends. When the line is tight and the potential for benefit exists, there is no way I could abstain, knowing the enjoyment I derive.
For others, this may not be the case. Whether you enjoy a glass or two a day and believe it has benefits or believe it is harmful and want to avoid completely, the important part is knowing the limitations and the dangers of overconsumption.