Why a Little Stress May Be Exactly What We Need
We have spent much of the modern era succeeding in making ourselves comfortable. We heat the house when we’re cold, cool it when we’re hot, eat when we’re hungry, sit when we’re tired, and take the elevator when confronted with the indignity of stairs. We surround ourselves with climate control, calories, chairs and conveniences until life begins to resemble a very pleasant waiting room.
Our cells, unfortunately, did not get the memo.
Human biology was forged in a world of intermittent difficulty. Food disappeared. Temperatures changed. Muscles worked. Hearts raced. Occasionally something with large teeth expressed an interest in us. We survived not because stress was absent, but because our bodies became remarkably good at responding to it.
This phenomenon is called hormesis.
What Doesn’t Kill You
Hormesis describes a biological response in which a small or moderate stress stimulates adaptation, while a larger dose of the same stress causes damage. Exercise is probably the most familiar example. Lift a heavy weight and you temporarily disrupt muscle fibers. Run hard and you deplete glycogen, disturb cellular energy balance and increase production of reactive oxygen species. None of this sounds particularly healthy.
And yet the body responds by repairing the damage and preparing itself for the next encounter. Muscle becomes stronger. Mitochondria become more capable. Insulin sensitivity improves. Antioxidant defenses increase. The cardiovascular system adapts.
The sequence is beautifully simple: Stress → signal → repair → adaptation → greater resilience
Exercise doesn’t make us healthier because it is comfortable. It makes us healthier because we recover from it. That last part matters enormously, because hormesis is not the proposition that stress is good. It is the proposition that recoverable stress can be good.
Your Mitochondria Need Something to Do
Nowhere is hormesis more fascinating than inside the mitochondria, the tiny power plants within our cells that convert energy from food into ATP, the chemical currency that powers much of human biology.
During this process, mitochondria also generate reactive oxygen species, or ROS. For decades, ROS were cast almost exclusively as molecular villains. They can damage proteins, lipids and DNA and contribute to aging and disease, so the logical conclusion seemed obvious – eliminate them whenever possible. Thus began our long love affair with antioxidants.
If oxidation was bad, antioxidants must be good. More antioxidants must therefore be better. Biology, as usual, declined to be that simple.
We now understand that small, transient increases in ROS also function as signals. They tell the cell that something challenging is happening and that it had better prepare itself. This produces a particularly elegant form of hormesis called mitohormesis.
A temporary mitochondrial challenge can activate cellular pathways involving AMPK, sirtuins, NRF2 and PGC-1α. These signals increase our own antioxidant defenses, improve cellular repair, stimulate mitochondrial biogenesis and help identify and remove damaged mitochondria through mitophagy. In other words, a little oxidative stress can make the cell better at handling oxidative stress.
Ozone therapy is a wonderful example of mitochondrial hormesis. Major Autohemotherapy, or MAH, is one of the most widely used forms of medical ozone therapy. The procedure itself is surprisingly simple. A small amount of blood is withdrawn into a sterile bottle, exposed to a carefully measured mixture of oxygen and ozone, and then returned to the body through an IV. The ozone immediately reacts with fats, proteins, and antioxidants already present in the blood, producing a cascade of signaling molecules called ozonides. These molecules then communicate with cells throughout the body, nudging various physiologic systems toward adaptation and resilience. Hormesis.
Exercise Is Hormesis in Sneakers
If you want a practical hormetic intervention with an enormous body of evidence behind it, start with exercise. Exercise briefly creates exactly the conditions our comfortable cells would rather avoid: increased energy demand, mechanical stress, heat, ROS production and temporary metabolic disruption.
The body responds by preparing for the possibility that we might be foolish enough to do it again tomorrow. Resistance training builds muscle and bone. Aerobic exercise improves mitochondrial density and oxidative capacity. High-intensity intervals challenge the cardiovascular and metabolic systems. Even walking creates physiological signals that sitting does not.
The trick is dosage. A twenty-minute walk may be a useful challenge for one person while a marathon may be an appropriate challenge for another. Reverse those prescriptions and things become considerably less clever.
Hormesis follows a curve. Too little stress produces little adaptation, an appropriate amount produces resilience, and excessive stress produces injury. More is not always better.
Hunger Is Also a Signal
Our ancestors did not have protein bars in the glove compartment. They lived in a “feast or famine” world. Periods without food were unavoidable, and our metabolism evolved accordingly.
During periods of reduced nutrient availability, insulin signaling falls and cellular energy sensors such as AMPK become more active. Pathways associated with growth and nutrient abundance, including mTOR, become less dominant, while cellular housekeeping and recycling pathways such as autophagy may become more active. The body temporarily shifts its emphasis from grow and store toward maintain, recycle and repair.
This helps explain some of the interest in intermittent fasting and time-restricted eating. But hormesis argues against fanaticism just as strongly as it argues against perpetual comfort. If a modest fasting interval creates a useful metabolic signal, it does not follow that starving yourself for thirty days is thirty times healthier.
Hormesis rarely rewards enthusiasm without judgment.
Hot, Cold and Otherwise Uncomfortable
Temperature provides another fascinating example. Heat exposure, particularly sauna, temporarily raises body temperature and activates heat-shock proteins, molecular chaperones that help protect, stabilize and repair cellular proteins. Cold exposure creates a different collection of responses involving sympathetic signaling, catecholamines, vascular adaptation and thermogenesis.
Neither requires turning yourself into a boiled lobster or joining a polar-bear club. The larger biological lesson is variation. Our physiology evolved expecting temperatures to change.
The modern environment offers something historically unusual: seventy-two degrees, twenty-four hours a day, twelve months a year. Comfortable? Absolutely. Evolutionarily normal? Not remotely.
Broccoli Is Trying to Kill You
Plants provide perhaps the most entertaining example of hormesis. Plants cannot run away, so when attacked they manufacture chemical defenses. Interestingly, many of the plant compounds we celebrate as “antioxidants” may benefit us not simply by neutralizing oxidants themselves, but by creating a mild cellular challenge that activates our own defense systems.
Sulforaphane from cruciferous vegetables is a classic example. It activates NRF2, which in turn increases the expression of numerous cellular antioxidant and detoxification enzymes. The sulforaphane doesn’t simply wander around the bloodstream heroically extinguishing free radicals. It rings the alarm, and our cells provide the fire department.
This concept, sometimes discussed under the broader umbrella of xenohormesis, may help explain why diets rich in colorful vegetables, herbs, spices, coffee, tea, cocoa and other phytochemical-rich foods are repeatedly associated with health benefits.
We may not merely be consuming antioxidants. We are consuming information.
The Antioxidant Paradox
Hormesis also helps explain why indiscriminately suppressing oxidative stress isn’t necessarily desirable. Exercise produces ROS, and those ROS participate in the signaling that produces adaptations to exercise. It therefore follows that flooding the system with large doses of antioxidants around every workout could potentially dampen some of the very signals we are trying to create.
That doesn’t mean vitamin C or vitamin E is bad. Both are essential nutrients. It means that nutritional sufficiency and pharmacologically flooding the system with antioxidants are not the same thing.
Our endogenous antioxidant systems, including glutathione, superoxide dismutase, catalase and others, are astonishingly sophisticated. Sometimes the best way to strengthen those systems isn’t to protect them from every challenge. It is to give them something reasonable to respond to.
Stress Plus Recovery
There is an important warning buried inside all of this: chronic stress is not hormesis.
Sleeping five hours every night is not hormesis. Overtraining is not hormesis. Chronic starvation is not hormesis. Living in a sauna while fasting after an ultramarathon is not longevity medicine. It is a cry for help.
Hormesis requires recovery. Exercise followed by rest. Heat followed by cooling. Fasting followed by nourishment. Stress followed by restoration. Without recovery, an adaptive stimulus simply becomes another source of physiological damage.
This also explains why the hormetic dose is different for everyone. The same stress that strengthens a healthy 25-year-old may overwhelm someone who is older, ill, malnourished, sleep-deprived or already physiologically stressed. The dose makes the medicine, and sometimes the dose makes the poison.
A Little Less Comfortable
The larger lesson of hormesis has nothing to do with mitochondria. We have engineered inconvenience out of our lives with extraordinary efficiency. We don’t have to walk. We don’t have to lift. We don’t have to tolerate hunger. We rarely have to experience heat or cold. Food arrives through a car window. Packages arrive on the porch. Machines carry us upstairs.
Civilization has been spectacularly successful at removing physical hardship. Our biology may be paying a price for that success.
The answer isn’t to abandon civilization and chase elk barefoot through the Rockies. It is simply to put a little purposeful difficulty back into life. Lift something heavy. Walk somewhere you could have driven. Get your heart beating hard occasionally. Eat vegetables that taste faintly suspicious. Miss a meal once in a while if it is appropriate for you. Get hot. Maybe get a little cold.
Then eat well, sleep deeply and recover.
Author
Scott Rollins, MD, is Board Certified with the American Board of Family Practice and the American Board of Anti-Aging and Regenerative Medicine. He specializes in bioidentical hormone replacement for men and women, thyroid and adrenal disorders, fibromyalgia and other complex medical conditions. He is founder and medical director of the Integrative Medicine Center of Western Colorado (www.imcwc.com) and Bellezza Laser Aesthetics (www.bellezzalaser.com). Call (970) 245-6911 for an appointment or more information.
