Hormesis, Exposing Yourself to a Stress to Create a Benefit
Part 6 of 7
Hormesis is proving to be an incredibly valuable tool in our health arsenal. From cold exposure to psychedelic micro-dosing and everything in between, the field has a lot of promise. Even some molecular hydrogen experts, such as Tyler W. LeBaron, have proposed that the mechanism could be hormetic-like effects.iii While there are many forms of documented and beneficial hormesis, we are going to address only seven during this series. Articles will be released weekly, as usual, and we encourage you to reach out to either our team or your MD with any questions. Some of the practices, such as the previously mentioned psychedelic micro-dosing protocols, while potentially promising are still illegal and could be far more dangerous if administered incorrectly. Others, such as exposing a toddler to nut proteins when a nut allergy is present, should only be practiced under the care and guidance of a licensed medical practitioner. While I have met many intelligent, reasonable and caring alternative practitioners, they typically do not have the training required to undertake this. Politics and philosophy aside, when a young life- or any life- is on the line and a risky protocol is tackled, it is necessary to seek out the most qualified to ensure safety. Each of the tools we will explore can be a great ally in your quest for health and longevity, but like any stressor, could be catastrophic if used incorrectly. Remember, there is no single “magic pill” to stave off the damages of aging and as currently stands, there is no complete routine or strategy to radically extend life. The best we can do is strive to win small victories, to extend our health span as long as possible in order to enjoy our lives, pursue our passions, and spend more time with our loved ones. Part 6 in our series addresses one of the most commonly indulged modes of hormesis. Unfortunately, the vast majority tend to overdue it, most of the time.
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 favoured 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 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,iii osteoporosis, and mortality, with higher intake sharply increasing risks.ivvvivii 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 behaviours in a two phase, or biphasic, dose-dependent manner with low doses being stimulatory and higher doses being inhibitory.viii This has been observed in studies on anxiety and depression, with low levels improving conditions and high intake aggravating proper mood function.ixThis can be quite problematic, as those suffering from depressive disorders are more likely to drink to excess, exacerbating their condition.x Since alcohol also tends to alter “the reward center” of our brain, increasing our proclivity to gamble and take chancesxi, 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 testosteronexiixiii and chronic overtraining significantly decreases testosterone,xiv mild to moderate alcohol intake has shown to increase testosterone in both menxv and male rats,xvixvii while chronic consumptions decreases itxviiixix 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 proteinsxx as well as endothelial nitric oxide synthase (eNOS) production.xxi 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.xxii
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. xxiii
mTOR signalling 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.xxivxxvxxvi A great review of alcohol and aging, covering ethanol’s role with mTOR and FOXO3a can be found here.xxvii
Ethanol has shown to promote neurogenesis in the hippocampus of rodents consuming moderate amounts of alcohol without triggering apoptosis,xxviii 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.xxix It also damages dendrites, the end of our neurons needed for “proper communication” through our brain, specifically in regions that moderate “reward.”xxxFurthermore, 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.xxxi
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 diseases.xxxii 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.xxxiii The differences were quite significant and complete suppression was only seen at three times the levels of activation. When that two glasses of wine turns to 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.xxxiv Even the use of alcohol for insomniacs has conflicting data, with some parameters improving and others, such as REM, decreasing.xxxv Anecdotally, I have found that if I drink my wine late at night after dinner and right before bed, even two to three glasses leaves 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.xxxvi 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.xxxvii Furthermore, resveratrol shows positive results in studies pertaining to diabetes, such as its effect in type II diabetic rats.xxxviii
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.xxxixPerhaps 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.xl Further evidence remains lacking, but since red wine is my favoured beverage, I will jump all over this, actively acknowledging my selfish confirmation bias.
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.
Next week, the form of hormesis we are the MOST excited about.