Hormesis: 4 Ways Stress Makes You Stronger

If you’re like most people, you probably think of stress as something entirely negative.

You get stressed out from clocking too many hours at work.

Stressed from not sleeping enough.

Stressed from the day-to-day tasks and obligations that characterize life in the 21st century.

Stressed from feeling stressed.

If you’re reading this blog, it’s more than likely that you have some high-achieving, type-A tendencies. In the spirit of optimization, you love the challenge of pushing yourself mentally and physically, and welcome the stress, the discomfort, and the difficulty that serve as milestones down the path to reaching your goals.

Now, embracing discomfort and difficulty isn’t just an effective mindset for growth, it’s also a concept that is literally hardwired in your body; it’s a scientific phenomenon called hormesis and it’s the reason why stress and hardship can actually be beneficial.

In this blog I’m going to talk about how the innate stress response known as hormesis is one of the body’s most important hardwired mechanisms to improve your fitness, your health, your intelligence, and it can even make you live longer.

When Stress Works For You

Your body has evolved to withstand and adapt to all different types of stress, from the food you eat, the time you eat (or don’t eat), the exercise you engage in, to the temperature you’re exposed to.

If there was ever proof that the obstacle is the way -- that in the work lies the reward -- look no further than your own physiology. Exposure to periodic bouts of stress causes your body to supercompensate, which means it responds to that stress by getting stronger/smarter/more resilient/more resistant to disease.

Marcus Aurelius was right when he said, “The impediment to action advances action. What stands in the way becomes the way.”

Think about all the significant accomplishments you’ve had in your life.

How many of them came easy and stress-free?

If you’re being honest, that answer is probably “none”. Or certainly not very many.

Getting better at things almost always entails discipline, embracing discomfort, and ultimately, stretching your abilities so you can level-up in life.

• IF you want to get stronger, THEN you have to progressively increase the weight.
• IF you want to get smarter, THEN you must challenge yourself and keep moving the goal post forward.
• IF you want to get healthier, THEN you need to change your habits, which is hard.
• IF you want to live to be 100, THEN you might be able to do it, but it will require discipline, strategy, good genetics… and some luck.

In each of these examples, the derived benefit is the result of some form of stress or hardship.

When Nietzsche said, “That which does not kill us makes us stronger”, these are precisely the kinds of examples he was referring to, but in truth, he might as well have been talking about hormesis all along.

Definition: “[Hormesis] is process of conditioning and adaptation in which low levels of stress stimulate or upregulate cellular and molecular pathways that improve the capacity of cells and organisms to withstand greater stress.” (1).

Some of the key benefits and categories of hormesis that have been observed in the scientific literature include (2):

• Healthy immune cell proliferation
• Fecundity
• Enhanced tissue repair
• Behavioral/Learning
• Disease/Injury Resistance
• Healthy Aging/Longevity

See, hormesis represents a general adaptive strategy through which biological performance is enhanced and mediated. Exposure to certain compounds and chemical agents that would otherwise be harmful at higher amounts, can actually incur significant health benefits with mild, intermittent exposure (trace vitamins, minerals, phytochemicals and certain nutrients) or controlled, acute-exposure (physical exercise, exposure to heat stress, periods of fasting or calorie restriction).

Take this paper from 2008 that was published in the Laboratory for Cellular Aging, Department of Molecular Biology, University of the Aarhus in Denmark:

“Single or multiple exposure to low doses of otherwise harmful agents, such as irradiation, food limitation, heat stress, hypergravity, reactive oxygen species and other free radicals have a variety of anti-aging and longevity-extending hormetic effects.” (3).

The benefit of hormesis lies in the dose-response relationship, or in toxicology parlance, a ‘biphasic dose response’. As the toxicological axiom goes, “the dose determines the poison”, therefore, in order for the body to respond to a stressor and adapt favorably, the right dose has to be administered.

Whereas chronic stress or exposure to toxic agents can significantly undermine your best efforts to optimize your health, acute, controlled bouts of stress can actually have the opposite effect -- they have a significant additive effect on your health, bolstering resilience, immune function, and increasing the body’s ability to adapt to stress.

There are thousands of studies and over 5,000 known dose-dependent hormetic compounds, but below are four of the best ways to use stress to your advantage that you can implement today.

1. Nutritional Hormesis

What would you say if I told you that many of the supposedly “healthy” compounds you find in fruits and vegetables were actually toxic?

You’d probably tell me to go suck eggs or pick up a book.

Well, these mildly toxic compounds are called phytochemicals and they exist in plants to give them their vibrant, colorful complexion. They also act as natural defense mechanisms to ward of predation and protect plants from oxidative stress.

To organisms like fungus, insects, and other pests, these phytochemicals are toxic enough to deter them from attacking the plant. For humans, however, their mildly toxic effects have a compensatory adaptive response on a cellular level which contributes to favorable health outcomes such as lower risk of cancer, cardiovascular disease, and neurodegenerative disease -- all benefits we attribute to a high fruit and vegetable intake.

Think about some of the most popular “superfoods” of our day: blueberries, dark chocolate, turmeric, red wine, green tea, broccoli. All of these foods contain hormetic compounds that activate adaptive stress response pathways (4).

• Blueberries contain protective, antioxidant compounds called anthocyanins
• Dark chocolate is rich in a class of antioxidants called catechins
• Turmeric’s main active ingredient is the potent anti-inflammatory curcumin
• Red wine is often considered healthy because of the antioxidant, resveratrol
• Green tea is rich in the catechin EGCG
• Broccoli is abundant in sulforaphane, a compound that most notably protects neurons from oxidative stress.

Those are just a few examples of foods that are considered “healthy” principally because they contain substances that, while mildly toxic in small amounts, activate pathways in the body that have beneficial hormetic effects ranging from a bolstered immune system, decreased inflammation, and enhanced cellular function.

2. Exercise

As tired and cliche as the expression, “no pain, no gain”, is, there’s a reason people continue to say it.

The act of physical exercise is about inducing damage to the body -- especially if we’re talking weight-lifting. Weight training is perhaps one of the most elegant examples of how hormesis works. When you’re blasting out reps, you are deliberately fatiguing and damaging your muscle tissues. You’re dripping with sweat, your heart rate is pounding, and as you approach failure, your muscles are literally brought to their maximal potential to move the weights.

In the moment, there are a host of biomarkers that at any other time would signify that your body is under a tremendous amount of stress. Inflammation and oxidative stress would be off the charts. The stress hormone cortisol would be elevated (5). Your very musculature would be riddled with tiny micro-tears and impingements, bathing in a soup of chemical messengers and hormones calling for reinforcements to repair your torn up muscles (6).

Weight training in and of itself puts a massive amount of stress on the body, but that being said, this stress is in fact the entire point of lifting weights. You deliberately engage with the physical discomfort and stress, and once you finish your last working set, and leave the gym sore, tired, and fatigued, a few interesting things start to happen:

• A cascade of anti-inflammatory compounds respond to the damage to simultaneously treat the inflammation, heal and repair damaged tissues, and flood a variety of antioxidants to the injury site (7).
• Your central nervous system adapts to the bout of exercise in a compensatory fashion, and anticipates that the next workout will be at least as challenging, if not more so (8).
• DNA repair is enhanced (9)
• Heat shock proteins are activated which protect against molecular damage and accumulation (more on this in the next section) (10).
• Brain function increases

From an evolutionary standpoint, when your body is under a significant amount of physical stress, it adapts to the situation by overcompensating -- i.e. generating more muscle tissue, making you stronger and better able to survive. So that next time, that your body will be better able to endure the same physical challenge, and ideally, improve performance.

While a single bout of intense exercise can make your blood panel look like someone who’s stepped in front of a bus, the body is able to rest, recover, and adapt to the stress and ultimately improve during that next workout.

3. Heat Stress

Just as physical exercise is a way to develop resiliency, exposing yourself to extremes in temperature for limited periods of time has some similar, overlapping effects.

Thermic conditioning is a beneficial form of heat stress that has several benefits involving endurance capacity and overall fitness such as:

• Improved cardiovascular mechanisms and lower heart rate (11)
• Increased blood flow to skeletal muscle and other tissues (12)
• Reduced rate of glycogen depletion
• Increased red blood cell count
• Increased efficiency of oxygen transport to muscles (13)
• Improved insulin sensitivity and production of growth hormone (13)

Aside from heat stress’ application to improvements in fitness, it also has a robust effect on stimulating heat shock proteins (HSPs) which are known to increase longevity and bolster stress resistance (14). Intermittent heat exposure activates HSPs that can reduce oxidative damage, repair damaged proteins, and support cellular antioxidant capacity (15). In flies and worms, exposure to heat treatment was shown to activate HSP’s and increase lifespan by up to 15% (16). Granted, we can’t always extrapolate findings from animal studies to human populations, so you have to take this with a grain of salt, but these results can give us clues for further research as to how humans would respond

Lastly, heat stress may have a potent effect on brain health, with benefits including (17):

• Improved attention and focus from the release of norepinephrine
• Increases in prolactin, which causes the brain to work faster by enhancing myelination and helps to repair damaged neurons.
• Increases BDNF, which causes the growth of new brain cells, and improves the ability for you to learn new information and retain it.
• Reduction in certain types of depression and anxiety.

4. Calorie Restriction and Intermittent Fasting

Intermittent fasting (IF) has become something of a darling in the health community. While it originally gained in popularity as a dieting strategy and lifestyle to manage body composition and food intake, it has since taken the spotlight as one of the most compelling strategies to increase lifespan.

IF is nothing more than reducing the amount of hours that you’re in a “fed” state per day. From the moment you put down the fork to the moment you take another bite, you’re fasting. You do it every night when you go to sleep.

With respect to life-extension properties, the main hormetic mechanisms involved are thought to be:

• Reductions in growth factor IGF-1 (low levels are associated with increased longevity) (18).
• Inhibition of mTOR (a major pathway for cellular growth and reproduction) (19).
• Increased autophagy (thought to be a survival mechanism responsible for removing damaged proteins, organelles, pathogens, and other cellular debris) (20).
• NRF2 activation (a transcription factor that expresses a number of genes involved in antioxidant status, cellular protection, and DNA repair) (21).
• ActivatIon of FOXO3 (the so-called “longevity gene” and principal pathway that regulates a host of genes involved in DNA repair, tumor suppression, anti-inflammation, antioxidant status, immune function, and more) (22).

When you are in a “fed” state, many of these beneficial pathways are completely shut off, but when you’re fasting, all of these pathways are switched.

Calorie restriction (CR) shares some overlapping features with IF. For instance, long-term CR is also thought to pose a chronic, mild stress response in the body, which has been shown to activate HSPs, modulate antioxidant activities, and induce autophagy (23). So, when you read headlines touting intermittent fasting or calorie restriction as the fountain of youth -- the supposed “real way” to slow the aging process -- it’s because intermittently depriving the body of energy, or adhering to a long-term reduction in food intake, induces a mild state of stress which switches on a cascade of beneficial, aging-related processes.

On the one hand, the evidence is overwhelmingly positive in animal studies that CR and IF unequivocally extend lifespan. On the other, there haven’t really been any conclusive human studies looking at life-extension. One of the main reasons is that controlling people’s lives over the course of years, or decades simply isn’t feasible within the confines of rigorous scientific investigation (24).

That being said, there is ample human research showing that both CR and IF have favorable effects on aging-related parameters involving the downregulation of growth factors, metabolic risk factors, and oxidative damage, as well as the upregulation of important reparative processes (26). So for that reason, both protocols have extensive evidence showing that you can greatly improve your healthspan and quality of life, but the jury’s still out on whether you’ll actually live longer.

Wrapping It Up

If you made it this far, you’ve just completed a mildly stressful bout of mental gymnastics -- and hopefully you learned something in the process. You know that the body actually thrives when subjected to certain types of stress. It’s the reason why we encourage our kids to play in the mud and get dirty: exposure to a wide variety of mildly stressful bacteria and germs is actually one of the best things you can do to develop a strong immune system. Ditto getting vaccinated.

Sometimes a little stress or the right challenge is exactly what we need to grow and improve. Whether that means feeding your body with hormetic plant compounds, or stimulating the body to grow stronger from exercise, upregulating cellular cleansing pathways through fasting, or using heat stress to improve your fitness and brain health, hormesis is the underlying principle that explains why just the right amount of stress can optimize your health.

The human body is an incredibly dynamic, complex organism, and intuitively it makes sense that for it to function at peak capacity it needs to be conditioned and given the opportunities to adapt to stress so that it can become better, stronger, and more resilient to more stress.

Questions? Comments? Post them in the comments below and let us know your favorite way to leverage the hormetic response.