BY SHARON HORESH BERGQUIST, MD

One evening in late 2011, I found myself sitting alone in my office after a long day of seeing patients, sifting through dozens of charts and labs—at a crossroads. Despite how quickly I could move from room to room or how many patients I could see, I didn’t feel I was making a real impact on their health.

At the time, I hadn’t yet discovered the concept of hormetic stress—the idea that certain challenges can actually strengthen the body. Instead, I was caught in the cycle of treating symptoms rather than addressing the root cause.

We were having the same conversations every six months or so about the same problems, just escalating their medications. Their numbers were improving, and we were reducing risk of complications, but I knew that the underlying process of their disease would progress.

Like most doctors, I had the skills to confidently diagnose and treat a wide range of diseases, but my help was intervening far downstream from the mouth of the problem. I spent my time trying my best to slow the flow of symptoms when the real need was to fix the dam.

At the time, I had been practicing internal medicine for over a decade and had dedicated myself fully to becoming the best physician I could be. I was drawing on the skills I had developed during my residency at Harvard’s Brigham and Women’s Hospital, as well as the invaluable training I received from exceptional mentors at Harvard Medical School. Year after year, I received awards for excellence in patient care based on being in the top percentile in national rankings.

My peers consecutively voted me as one of the top doctors in Atlanta. However, I was so busy working long days and weekends that I didn’t have time to think about how we were measuring and defining “excellence.” That evening, all these thoughts overwhelmed me with frustration and helplessness.

From that day forward I set out to learn everything about health and longevity. I got up early most mornings before seeing patients and spent weekends diving into all the data I could get my hands on—research on topics of nutrition, stress management, and all matters of wellness. As my research went deeper, I stumbled upon something unexpected—something both cutting-edge and deeply ancient: paradoxical science showing that our bodies need stress to thrive.

Though grounded in millions of years of evolutionary biology, this concept of good stress is only now gaining recognition in modern medicine as a foundational principle of long-term health and vitality.

Hormetic Stress

When we think of stress, we usually associate it with unrelenting pressures—work deadlines, family demands, financial strain. This form of chronic stress is all too familiar, and when left unmanaged, it undermines both physical and mental health.

But through my deep dive into the science of resilience and repair, I came to a surprising realization: not all stress is harmful—some forms, when applied in the right dose—are essential to building health. This is the principle behind hormetic stress, derived from the Greek word meaning “to excite.”

Hormetic stress involves brief, low-dose exposures to challenge—like intermittent fasting, high-intensity exercise, or controlled heat and cold. These short, intentional stressors activate the body’s innate repair systems— triggering cellular adaptation and regeneration that strengthen our ability to withstand the more damaging effects of chronic stress.

Our need for stress is rooted in evolutionary biology. For millions of years, our ancestors endured harsh conditions—food scarcity, climate extremes, plant toxins, and constant threats. To survive, they evolved adaptive responses that turned environmental hardship into a signal to strengthen, heal, and protect. These survival mechanisms remain encoded in our DNA—triggered only when the body is sufficiently challenged.

But modern life has removed many of these beneficial challenges. Our temperature-controlled environments, sedentary lifestyles, and abundance of food have muted the very signals our bodies rely on to stay strong.

So, to thrive in today’s world, we must intentionally reintroduce these ancient stressors in safe, measured ways. Hormetic stress, when applied episodically and followed by recovery, acts as a training signal for your biology—improving resilience, enhancing adaptation, and slowing the aging process. Here’s a look at two effective hormetins—health-promoting stressors that trigger adaptive cellular responses—that you can readily incorporate into your everyday life.

Hormetin-Food “Toxins” as Medicine

You already know that eating your veggies—or an apple a day—is good for you. Fruits, vegetables, and other plant-based foods are rich in vitamins, minerals, and fiber, all of which help prevent disease, promote longevity, and support overall health.

But what you might not know is that the real secret weapon of plant foods lies in their natural chemicals, known as phytochemicals. To date, over 5,000 phytochemicals have been identified in fruits, vegetables, legumes, grains, nuts, seeds, and spices—and many more are only beginning to be studied in depth.

Phytochemicals are non-nutritive, meaning they don’t provide nutrition like protein, fats, or carbs. Instead, they function as molecular signals—activating pathways in our bodies that reduce inflammation, protect DNA, and support cellular repair. Think of them as tiny bites of medicine.

These compounds are most concentrated in the outer layers of plants, contributing to their vivid colors, distinctive flavors, and unique aromas. The deep pigment in blueberries, the vibrant orange of carrots, and the sweetness of a ripe strawberry all reflect high levels of phytochemicals. In fact, the stronger the taste and scent, the more phytochemicals a plant likely contains.

For many years, scientists believed the primary benefit of phytochemicals came from their antioxidant activity—neutralizing harmful free radicals. However, emerging research over the past two decades has revealed a deeper, more powerful mechanism: phytochemicals act as mild, controlled hormetic stressors that activate hormetic pathways— triggering adaptive responses that promote cellular repair and switch on genes linked to healthspan and longevity. In this way, phytochemicals deliver a hormetic boost that strengthens our biology over time.

So, we need phytochemicals—not so much to supplement something our bodies lack—but more because they activate different survival pathways and help us thrive in the face of stress.

And there’s a good reason for that. Phytochemicals evolved to help plants survive their own environmental challenges—extreme temperatures, nutrient scarcity, microbial threats, and hungry predators. Their survival depended on stress, too. In much the same way these phytochemicals strengthen plants’ defenses, they also enhance our own.

In essence, the stress that strengthens plants also strengthens us. Their ability to adapt to environmental adversity becomes our ability to adapt to modern life. While new hormetic phytochemicals are continually being discovered, many of the most powerful are already in our kitchens. I make it a point to include them in my diet—not just for their nutritional value, but because they help my body repair, adapt, and thrive.

Let’s review some of the most well-researched phytochemicals—and the everyday foods that deliver them.

Resveratrol. The connection between phytochemicals and hormesis first gained attention in the late 1990s with the discovery of resveratrol. At the time, researchers were investigating the so-called French Paradox—the observation that people in southern France had significantly lower rates of coronary artery disease despite diets relatively high in saturated fat.

This unexpected outcome was initially mis-attributed to their daily consumption of red wine, sparking widespread interest in resveratrol—a prominent compound found in the wine’s grape skins. However, like many phytochemicals, resveratrol is rapidly absorbed and metabolized in the body, leaving only trace amounts in circulation—far too low to function effectively as a direct antioxidant, as originally believed.

Over time, researchers discovered that resveratrol benefits health not by neutralizing free radicals, but by activating hormetic stress responses. In plants, resveratrol serves as a natural defense compound—a fungicide and antibiotic produced in response to threats like pathogens or environmental stress. The more stressed a plant is, the more resveratrol it produces.

The best part is, you can mildly stress your cells with this natural pesticide and build your resilience through many delicious options. You can get resveratrol from eating berries (eg, blueberries and cranberries), nuts (eg, pistachios and peanuts), and dark chocolate.

Resveratrol is the prototypic plant toxin that builds our healing and housekeeping systems through hormesis. It was the impetus behind discovering the other hormetic plant toxins on this list.

Sulforaphane. This phytochemical is found exclusively in cruciferous vegetables, such as broccoli, cabbage, cauliflower, brussels sprouts, kale, and arugula. These vegetables have evolved a clever defense mechanism involving an enzyme called myrosinase.

This enzyme converts sulfurcontaining compounds into protective phytochemicals when the plant is threatened. So, when the plant is damaged—say, by a chewing insect or a hungry human—the myrosinase is released, catalyzing a reaction that produces potent compounds such as sulforaphane.

Here’s a practical tip: Chop or blend cruciferous vegetables before cooking, as heat destroys the myrosinase enzyme. This mechanical preparation allows the enzyme to activate sulforaphane-producing reactions before it’s exposed to heat. The enzyme is also deactivated in frozen cruciferous vegetables, so you have to mix them with a small amount of fresh chopped or blended cruciferous vegetables to restore the enzyme and boost sulforaphane availability.

So, what happens when this toxin is released in our body? It activates Nrf2 (nuclear factor erythroid 2-related factor 2)—a master switch for our antioxidant and detoxification systems. Nrf2 controls the expression of our vita-genes—the highly conserved circuit of survival genes, which promote health and longevity by building cellular stress tolerance.

This is a perfect example of how a plant’s sophisticated defense works as our defense. Many plant “toxins” activate the master regulator Nrf2, which makes it a common mechanism by which phytochemicals stress our body just enough to help prevent the onset and progression of numerous chronic diseases.

Allicin. Found in garlic, onions, shallots, and leeks, allicin is a sulfur-containing compound that exerts its hormetic effects by temporarily increasing calcium influx into cells. It does this by opening pores in the cell membrane, allowing calcium to enter. T his rise in intracellular calcium activates signaling proteins that switch on genes responsible for producing growth factors—natural compounds that help the body remodel and regenerate in response to stress.

Both plants and humans have evolved systems to tightly regulate cellular calcium levels. In excess, calcium is toxic to cells, but in small, controlled amounts, it acts as a beneficial stressor—triggering adaptation and repair mechanisms that support long-term resilience.

Capsaicin. If you have ever put an entire chili pepper in your mouth at once, you have experienced firsthand how effective capsaicin is at deterring us from consuming this plant! Capsaicin is the chemical that sets your mouth on f ire when you eat spicy peppers, such as serrano or cayenne.

This toxin mainly builds cellular defenses by activating the anti-inflammatory stress response pathway. Capsaicin can also open pores in cell membranes to allow calcium in, which turns on genes that produce growth factors and enhance regeneration.

Despite all we know about phytochemicals, only about one in ten Americans consumes the recommended daily amount of fruits and vegetables. While much attention is placed on getting enough protein and essential vitamins, the most overlooked dietary deficiency may be in phytochemicals.

In fact, one of the largest epidemiological studies to date—spanning twenty-seven years and 195 countries—identified a lack of phytochemical-rich plant foods as the leading dietary risk factor for mortality worldwide, contributing to one in five deaths.

Of course, as with all stressors, dose matters. Even beneficial phytochemicals can become harmful if consumed in excess. Take green tea, for example: the compound EGCG (epigallocatechin gallate) provides powerful hormetic benefits at one to two cups per day. But at six cups daily over several months, EGCG can lead to liver toxicity.

In other words, phytochemicals are technically plant toxins—but in the low doses naturally present in a varied, plant-rich diet, they are not toxic. Instead, they act as biological signals, honoring the way our ancient physiology has been wired to use these molecular stressors to adapt, repair, and thrive in the face of modern challenges.

Hormetin–Cold & Heat

Exposing ourselves to extreme cold or heat isn’t something most people do willingly. It can feel uncomfortable—and in excess, it can be dangerous. But when done safely and in moderation, brief, controlled exposure to thermal stress can activate powerful biological responses that make us healthier, more resilient, and even mentally sharper.

Cold exposure builds resilience by activating a rapid and robust stress response. When skin receptors detect a sudden drop in temperature, they send a burst of signals to the brain, prompting a sharp spike in noradrenaline (also known as norepinephrine)—sometimes reaching levels up to five times higher than normal.

This sudden surge has immediate effects: increased energy, sharper focus, and elevated alertness. But the benefits go even further. Cold exposure—also called cold therapy or cryotherapy— also rapidly increases the “feel good” neurotransmitter dopamine levels by up to 250 percent!

Better yet, brief cold exposure triggers a stress response that activates your neurochemistry differently from the classic fight-or-flight reaction. In fightor-flight, the brain detects a threat and f loods the body with adrenaline and noradrenaline. This alarm state is then sustained by cortisol—keeping the body on high alert for longer periods.

However, during controlled cold stress, the neurochemical profile is different. While cold exposure does cause a spike in noradrenaline, the other major stress hormones that surge during fight-or-flight—adrenaline and cortisol—remain unchanged.

In fact, brief exposures a few times per week can actually lead to lower baseline cortisol levels in as little as four weeks.

Clearly, not all stress responses are created equal. Good hormetic stressors create a different biochemical profile in our body that benefits rather than harms— and thermal stress is one of the most accessible, powerful ways to harness this principle.

Another Advantage of Thermal Therapy-Activating Brown Fat

Ever wonder how kids can dash around in the dead of winter wearing just a T-shirt, insisting they’re not cold?

It’s not just stubbornness—they have an abundance of “brown fat,” a special type of fat that acts like the body’s built-in space heater, keeping them warm in chilly temperatures.

For a long time, scientists believed that brown fat was only the province of children and that it disappeared as we age. However, researchers at Harvard Medical School made a fascinating discovery: Using a technology called positron emission tomography (PET scans), they found that adults have brown fat, too!

While white fat is designed to store energy (calories), brown fat is designed to use it: brown fat rapidly burns energy to maintain body temperature. The discovery that adults have brown fat was hugely exciting because it opened the possibility of activating it to burn stored energy and speed metabolism.

Research now shows that the more brown fat you have, the healthier you’ll be. More brown fat is associated with lower body mass index, and vice versa. Brown fat is also associated with reduced visceral fat—the dangerous belly fat that releases pro-inflammatory chemicals that increase the risk of diabetes, metabolic syndrome, and heart disease.

We are just at the cusp of understanding this special type of fat, but it is clear that activating brown fat—and getting more of it—can improve metabolic and cardiovascular health by regulating blood sugar and lowering cholesterol.

Much like anything, if you don’t use brown fat, you lose it, and as you get older or develop conditions like obesity and diabetes, you have less of it. However, brown fat has incredible plasticity and adapts quickly. You can grow and activate brown fat regardless of your current health. By doing so, you can utilize your body’s ability to do all the amazing things I described and more: lower cholesterol, improve insulin sensitivity, and reduce the risk of diabetes and heart disease.

I cannot emphasize that enough.

So, how do you activate brown fat? All you need to do is expose yourself to cold temperatures. You don’t even have to take a freezing shower. Simply lowering your indoor thermostat can be effective. In one study, people who spent six hours per day in a 60-degree Fahrenheit room while wearing shorts and a T-shirt saw a thirty-seven percent increase in their brown fat volume after just ten days!

Clearly, when we nurture our evolutionary stress response, we build our resilience and make it possible to live with less pain, disability, and suffering. No matter where you are starting from, remember that your body is remarkably adaptable.

Nearly two millennia ago, Hippocrates, hailed as the father of medicine, observed, “The natural healing force within each one of us is the greatest force in getting well.”

____________________________________________

Sharon Horesh Bergquist, MD, is an award-winning physician, innovative healthcare leader, and visionary researcher renowned for spearheading a science-based approach to applying lifestyle as medicine. She has helped lead numerous clinical trials, including the Emory Healthy Brain Study.

Dr. Bergquist is widely published in peer-reviewed journals and has contributed to more than two hundred news segments in media outlets such as Good Morning America, CNN, ABC News, the Wall Street Journal, and NPR. She hosts The Whole Health Cure podcast and her popular TED-Ed video on how stress affects the body has been viewed more than six million times. She received her degree from Yale College and Harvard Medical School.

The above excerpt is adapted from The Stress Paradox: Why You Need Stress to Live Longer, Healthier, and Happier by Sharon Horesh Bergquist, MD. Copyright © 2025 by Sharon Horesh Bergquist. From Harvest Books, an imprint of HarperCollins Publishers. Reprinted by permission.