Why are certain things “good for us”? Why does lifting weights make us stronger? Why does running a mile on a regular basis improve our aerobic conditioning and allow us to improve our times? Why does skipping a meal every now and then increase insulin sensitivity, lower body fat, improve lipid numbers, and generally make us healthier? Why are plant polyphenols so consistently associated with health benefits?

The answer is hormesis. You see, back when Nietzsche said, “That which does not kill us makes us stronger,” he may not have been talking about the positive and beneficial physiological effects of exposing yourself to various stressors and toxins, but he could have been. All those things – the exercise, the fasting, the plant phytochemicals, plus more – stress our systems and force us to adapt to the imposed stress. Organisms, after all, like to maintain homeostasis, stability, and balance, and hormesis is ultimately about the push to maintain homeostasis in a changing environment. If the environment changes – say, because of a weight lifting session – the body must become stronger, healthier, better in order to maintain homeostasis and handle the situation next time it occurs. Best of all, you don’t just compensate for the stressor. You supercompensate. You get stronger/faster/healthier/more resistant to disease than you were before. Think of hormesis as your body “hedging its bet” and going a little above and beyond just to be safe.

Beginning with the discovery that administering small doses of poison stimulated the growth of yeast, researchers have found the hormetic response to be remarkably preserved across species lines. Fungi (PDF), bacteria, insects, plants and algae, and animals all show adaptive responses to stressors. To date, around 5600 “dose-response relationships satisfying evaluative criteria for hormesis” have been identified. Hormesis, it seems, is a fundamental part of being alive. What this means, of course, is that many things that we assume are good for us are actually “bad.” They are stressors that initially do “bad” things to our health in the short term but induce an adaptive response that improves our health in the long term. Here are some examples:

Exercise – If you were to run labs on a guy who had just lifted heavy things for an hour, doing full body compound movements with excellent form and intensity, and was dripping sweat, the numbers would look awful. Inflammatory markers would be elevated. Oxidative stress would be evident. Cortisol will likely be high. The muscles would be suffering from extensive microtrauma – tiny little tears amounting to physical damage. Subjectively, he’d be in pain, exhausted, sore, and generally unable to do much of anything except rest, sleep, eat, and drink. Provided he rests and eats and sleeps, however, the guy will get stronger and faster and fitter as a buffer against future stressors over the next few days. Those inflammatory markers? They’re ultimately a signal for his muscles to repair themselves and come back stronger than before. A single bout of exercise, then, is oxidatively stressful to the body, while regular exercise lowers the oxidative challenge. In other words, the stressor remains, but our ability to respond to it improves (PDF).

Calorie restriction/IF – Skipping meals, limiting calorie intake, and simply having less food than your body expects is a major stressor, but it’s a stressor that offers many health benefits. The lack of food doesn’t just promote leanness (and in the case of IF, lean mass retention), it also triggers autophagy (both neuronal and systemic) – the process by which cells clean themselves up and recycle all the unnecessary and dysfunctional junk that’s been accumulating within.

Plant phytochemicals – You know all those colorful plant pigments with an impressive track record on promoting good health? Evidence is accumulating that many of the polyphenols, phenolic acids, and other bioactive phytochemicals exert some of their health effects via hormesis. Instead of evolving expressly for the benefit of Whole Foods shoppers, phytochemicals exist to protect plants from oxidative stress and to ward off pests. That’s right: they are natural pesticides, plant toxins meant to keep bugs and other pests away. They won’t kill us, of course, but they will irritate us enough to induce a compensatory adaptive response at the cellular level that results in many of the benefits attributed to fruits and vegetables. If we were eating blueberries the size of Volkswagens we might not survive the anthocyanin overdose, but a handful or two appears to be perfectly safe and even healthful.

Cold water plunges – As I’ve mentioned before (though not using the “hormetic” word), cold water exposure can elicit an adaptive response. For example, although ice bathing was shown to increase oxidative stress markers in swimmers, the markers for endogenous antioxidant production also increased. Anti-tumor immunity also gets a hormetic boost from cold exposure.

Sunlight – Our tendency to tan in response to sunlight is a classic example of a hormetic response. The tan protects our skin from sun damage, reduces skin cancer, looks good, and indicates that we’ve generated vitamin D.

Radiation – Although most scientists assumed that ionizing radiation would adhere to the linear no threshold model (where even the smallest exposures to a toxin result in elevated risk of harm), there is growing evidence that low doses of radiation actually protect against cancer via hormesis.

We don’t know all of the mechanisms behind hormesis, but there is one likely candidate: NRF2.  NRF2 is a transcription factor that, once triggered, expresses a number of genes involved in antioxidant defense, detoxification, and cellular protection. Many of the stressors we’ve just discussed trigger NRF2, including exercise, calorie restriction, polyphenol consumption, radiation, and sunlight.

It should be emphasized that while a low or moderate dose often elicits a favorable response, the opposite is likely true of a high or protracted dose. Intermittent fasting can elicit major health benefits, improve lean mass retention, and boost fat burning; starvation will also cause major weight loss, but not in a good way. Twenty minutes of moderately strong sun gets you a mild tan and plenty of vitamin D; five hours of strong sun gets you a sunburn. During a single stressful life event, adrenaline and cortisol will increase and make you alert and hyperware of your surroundings; a year of chronic stress will wear you down and lead to adrenal fatigue. This is also why I talk about chronic cardio. The occasional acute bout of really tough endurance work is probably helpful to your fitness; it’s the chronic, constant, day-in, day-out endurance training that is not, that will break you down. Even NRF2 has a “dark side”; its over expression will increase the resistance of cancer cells to chemotherapy.

Well, what do you think, folks? Personally, I’ve always found the hormetic response a valuable tool for viewing and assessing the world and all its myriad stressors. We’re bound to run into some of them – maybe all of them, at some point – and it’s nice knowing that there’s a real, quantifiable physiological phenomenon that explains how the hard times we all endure may not be in vain and may in fact actually make us stronger, healthier, faster, fitter, and better. You can’t help but be a glass half-full type of person when you filter many of life’s crazy headaches through the concept of hormesis.

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