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 LeBaron have proposed the mechanism could be hormetic like effect.i, ii
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 these 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, 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 1 in our 7 part hormesis series addresses perhaps the easiest strategy, cold exposure. It's a strategy that is unlikely to be overdone and requiring minimal effort while providing significant benefits.
Cold Exposure and Cold Therapy
Cold exposure can be either a painful experience or a pleasant experience depending on how you tailor your routine. Personally, I love cold exposure. Whether it be whole body cryotherapy chambers, a cold shower in the morning, or a fast and hard workout outside when it’s cold enough to see my breath, the results are invigorating.
The cold exposure I’m talking about takes your breath away at first, then charges you full of energy. It also is easy to recover from and warm back up once taken out of the environment. In fact, one human study recently published concluded
“ It is noteworthy that the largest physiological changes occurred during the first 30 minutes of cold exposure when the participants felt less discomfort” .iii
This is the cold exposure you want, this is the cold exposure you benefit from.
The cold exposure I detest- that everyone detests- is that slow chill that builds, and cools you to the bone. That cold feeling you can’t get over. In fact, this type of cold exposure, chronic cold exposure, has shown to have the exact opposite effect. In a study just published a few months ago it was linked to obesity and glucose dyshomeostasis.iv
Take for instance this study on pigsv where piglets exposed to 4c temperatures for 10hr a day converted their white adipose tissue to brown with activated thermogenesis- a key step for converting fat to energy and heat- and chronically exposed piglets that endured 8c temperatures for 15 days straight actually accumulated more white adipose tissue- the bad fat resistant to being burned off, as a defense to protect against the cold. Both groups were exposed to temperatures much lower than the body for extended periods, however, only the intermittent group received the benefit.
Just like we advise with hydrogen water, cold exposure requires intermittent exposure. Where intermittent exposure shows a benefit, continuous cold exposure shows the opposite effects.
Cold exposure is a bit of an exercise mimetic. In fact, the ‘exercise hormone’ irisin has been linked to many benefits, just recently even it has been suggested as having protective effects against the development of Alzheimer’s.vi
Cold exposure may release irisin easier than working out, with one study suggesting as many calories are burned in 10 minutes of shivering as compared to 60 minutes of cardio, with the calorie-burning being driven by irisin and FGF21 release.vii (as a note Molecular Hydrogen, specifically drinking hydrogen water, which as previously mentioned is another potential exercise mimetic, has also been linked to FGF21 release).viii
Both exercise and cold exposure have been linked to increased mitochondrial biogenesis, which is important to increase energy in our bodies and increase our metabolic capacities. As a note, other hormetic agents in this series have been shown to increase mitochondrial biogenesis as well.
While interest in the biohacking community has grown over recent years for some of the benefits we’ve spoken about above, cold exposure is most commonly used to blunt acute inflammatory responses. Practitioners, trainers, and ‘moms’ alike have long been prescribing ice packs for everything from burns to sprains, aches, and pains.
It is one of the four standard procedures following a sprain or tear- RICE, rest, ice, compress and elevate (although a pair of very positive case studies using our hydrogen tablets soon to be published, and a planned trial, make the case of using topical hydrogen water instead of RICE).
Despite being most well known for its’ use post-injury, cold therapy has had mixed results in research on this topic. Perhaps one of the issues is inconsistent methods pertaining to how cold constitutes cryotherapy, and for what duration. Further, the evidence that cold baths or whole body cryotherapy can sufficiently improve muscle recovery for athletes is also lacking. Let’s take a look at the evidence in a couple of interesting areas:
Like most hormetic agents, cold exposure has shown very preliminary evidence in many neurological outcomes. While I caution that this is very, very green science, as green as it gets, and should not, under any circumstance, be taken as a suggestion to replace any existing treatments recommended by a licensed medical practitioner, it is interesting nonetheless and I have personally experienced mood elevation from cold exposure.
One small study showed a group participating in winter swimming had improved mood, and reduced pain in those suffering from ailments, although I caution that this was not (and could not) be properly double-blinded. Another using whole body cryotherapy saw improvements, but again the size was limited, it wasn’t controlled and wasn’t blinded.
Another published hypothesis outlines how cold exposure, or specifically cold showers, could potentially mitigate depression. Again, this is simply a hypothesis that has not been validated. Another case study on a single participant showed benefits that were recently published in the BMJ. A review on various forms of hydrotherapy rightfully concludes there is inadequate evidence to draw any conclusions and that more study is needed.
Evidence in animal models, while complimentary overall, is mixed. Take for instance this study on rats that had improvements in one gender and declines in the other. I am also careful to draw conclusions or leaps from changes in various functions from animals to humans, as often they do not translate- and when they do ( cold exposure, for instance, has altered norepinephrine in rodents and humans and this review on all hormonal changes observed in human subjects via cold exposure), the results are often much more complicated than we would have thought.
Even hormones associated with happiness such as serotonin have shown to increase aggression when artificially bred in fruit flies, while a meta-analysis on human evidence has found the relationship with serotonin and aggression to be contradictory and incredibly complex:
and the human review, from conclusions:
“Contradictory findings, unreliable measurement, and a high degree of complexity leave our overall finding of a small inverse correlation between serotonin and human aggression open to multiple, equally plausible interpretations.”
Body composition & Metabolism
As discussed in the introductory paragraph, some of my first and early interest in cold exposure related to brown adipose tissue conversion or “BAT”, also referred to as ‘Beige” when white has been converted to a brown-like adipose tissue. BAT tissue is very easily converted to heat energy via thermogenesis, imagine little droplets of fat in a sack that can slowly convert to heat and be released. White adipose tissue, on the other hand, is like having a giant block of fat in the same sack. The entire block becomes resistant to change. Imagine if it was ice- 100 small ice cubes will melt much faster than 1 giant block of ice.
While the mechanisms are very different, the results are comparable in a basic sense. As we get older, we accumulate more and more white adipose tissue or WAT. This tissue is resistant to ‘melting away’ into heat energy, and in fact, often muscle wastes away first. This leads to the condition often referred to as ‘skinny fat’, which is hazardous to our health.
Cold exposure has in fact shown to increase BAT activation and non-shivering thermogenesis. In fact, it may work by the same methods that exercise does, namely irisin and FGF21 (https://www.ncbi.nlm.nih.gov/pubmed/26022904 ), but I will caution the evidence is much better in other animal models than in humans. This isn’t surprising, as we have ‘cured’ rodents of obesity more times than I can count. There are literally dozens of molecules that have shown to dramatically activate thermogenesis in mice or rats and they are resilient enough to deal with the rise in temperature.
In listening to Dr. Rhonda Patrick’s podcast on cold exposure, and don’t get me wrong I enjoy listening to her show and appreciate her platform as a resource, I was left with a rebuttal to her comments on BAT and UCP1, etc. Humans have dramatically lower levels of BAT than rodents, and uncoupling proteins are far less relevant. On top of that, molecules that drive this often have high toxicity and are not tolerable.
While a ‘magic pill’ to cure obesity is really attractive and exciting, the closest we have come to is a now-banned illegal good called 2,4-Dinitrophenol or ‘DNP’. DNP works. You will drop loads of weight. Life will be hard, your energy expenditure will become very inefficient. Getting out of bed will be a task, and when you do you will find you possibly ruined your mattress from sweat. This is just the tip of the iceberg.
As Wikipedia bluntly puts it “Chronic oral exposure to DNP can lead to the formation of cataracts and skin lesions and has caused effects on the bone marrow, central nervous system, and cardiovascular system.”
That isn’t even the worst of it. DNP will lead to death in even low doses, and it is not from the toxicity. It is from the rise in body temperature created by the very uncoupling and thermogenesis that allows it to be so effective.
"The factor that limits ever-increasing doses of DNP is not a lack of ATP energy production, but rather an excessive rise in body temperature due to the heat produced during uncoupling"
“Accordingly, DNP overdose will cause fatal hyperthermia, with body temperature rising to as high as 43.1 °C (109.6 °F) shortly before death. In light of this, when it was used clinically, the dose was slowly titrated according to personal tolerance, which varies greatly”
Wow, what a kick in the teeth for anyone wanting a miracle diet pill, huh? Even if we find one that works in this manner, as it becomes more effective it will kill you. We are fragile beings, and we need to take this into consideration.
BAT activation is something I am very, very interested in, and have spent north of 1000 hours reading on while conferring with experts in bioenergetics I have become acquainted with and formed friendships with. I have been n=1 on MULTIPLE experimental dosing protocols, incrementing, on molecules to drive excess energy, or act as uncouplers, but would never dare to take DNP. (I also personally participate in cold exposure, as I have noted).
The trick is finding what works the best, in the safest manner, and for many, maintaining affordability. This leaves us with options that may contribute to slight weight loss under controlled diet and activity, but certainly not a miracle. As exciting as the prospect would be, we aren’t particularly close. Look out for my blog on BAT activation, metabolism, and experimental (and approved) pharmaceuticals regarding obesity in the coming months.
So far, the better something works the more potential harm it can do. However, look out for the release of my own stack, Fighting Chance, that I am currently developing based on my n=1 experimentations and research on the topic. Fighting Chance is not going to be a miracle, but it is what I have developed based on the best evidence for efficacy balanced with the lowest risk of any side effects. As I am always safe, safe, and effective- but safe, first.
As a final note on this topic, I do encourage you all to try cold exposure, even for BAT activation. I just want to caution you it is NOT a miracle and DO NOT expect to lose a ton of weight by only implementing this. It is a free or relatively inexpensive tool to add to your arsenal.
Hormesis - Cold Exposure Conclusion
Cold therapy is a great tool that shows a lot of promise for brown adipose tissue activation (although as I’ve discussed the hype on this is greater than realized benefits will be), triggering thermogenesis and releasing FGF21 and irisin. While much of the research on this is in its’ infancy, being done in rodents and pigs, some human study has been completed. Research on athletic recovery and injury recovery is mixed.
Personally, I practice cold therapy multiple times a week and while I haven’t noticed any dramatic improvements in weight loss, and can say I have found it largely ineffective for muscle soreness, I notice a substantial rush of endorphins and feel a charge of energy. In fact, I would rate the energy burst as significantly higher than consuming caffeine in the morning. In the summer I rely on waking up with a cold shower, and that does work a bit, but right now in the wintertime waking up and feeling the cold stone on my feet as I get my heart racing with a quick round on my Thai bag is exhilarating. It cuts through any grogginess and motivates me for hours.
Cold therapy is easy, in many cases free and without any serious risks if administered in a reasonable and appropriate manner. While it isn’t the ‘miracle therapy’ spas and cryoclinics claim, it is full of potential benefits that shouldn’t be ignored.