The Science of Good Stress

By 2011, Sharon Horesh Bergquist, MD ’97, was frustrated.

After more than a decade as a physician, she found herself having the same conversations over and over again with her patients with chronic diseases. Her frustration was not with her patients but with her feeling that she wasn’t addressing the underlying causes of their health problems.

“I had all this knowledge about physiology and the pathways in our body that lead to disease, but I wasn’t applying that knowledge to prevent disease,” she writes in her new book, The Stress Paradox. “I spent my time trying to slow the flow of symptoms when what they really needed was for me to fix the dam.”

Her frustration sparked an interest in learning as much as she could about how to prevent chronic diseases from taking hold in the first place. In 2018, she founded the Emory Lifestyle Medicine and Wellness Program, and she developed a teaching kitchen to help people learn to cook healthy meals. All the while, she continued to study the literature on chronic disease prevention and conducted her own clinical studies as well.

Her research led her to an unexpected conclusion: one problem many of her patients faced was a lack of exposure to certain types of stress. Bergquist had stumbled upon the science of hormesis, which she defines as the process by which “certain stressors — the right kind, at the right intensity, and for the right duration — activate built-in defenses that protect, repair, and regenerate our bodies.” For Bergquist, who says she had been a “poster child” for the message that all stress is harmful, the long history of research on hormetic stress came as a surprise. “Lack of good stress is a new risk factor that threatens our health,” she writes. “This hardwired process is vital to how we, and all living beings, survive and thrive.”

In The Stress Paradox, Bergquist dives into five types of hormetic stress: exposure to phytotoxins by eating plants; exercise; exposure to cold and heat; brief, intermittent periods of fasting; and emotional or mental stress. She says that each of these has, to some extent, been engineered out of many people’s lives, and each has the potential to provide health benefits if reintroduced thoughtfully. In addition to providing detailed explanations of the science of hormesis, she offers suggestions on how to take advantage of hormesis using simple interventions. At the same time, she expresses discomfort with the way some of the topics she covers are discussed and marketed by the wellness industry.

Bergquist, now the Pam R. Rollins Professor of Medicine at Emory University School of Medicine, talked with Harvard Medicine editor Amos Esty about her research into hormesis and how it has changed the way she practices medicine. The interview has been edited for length and clarity.

Why did you start digging into this?

I’m fascinated by the body’s innate ability to heal and our natural defenses against disease. As a primary care internal medicine physician, so much of what I manage day to day is chronic disease. I realized that instead of just helping people treat these diseases, I could be of greater service if I could help people manage and even reverse their diseases — and better yet prevent them in the first place through lifestyle.

This research around hormesis is about more than just using stress to build resilience. The same pathways that are activated that help us build resilience are the ones that help us counter the processes and pathways that lead to disease and aging. So, for me, this became the most powerful tool that we can add to our lifestyle to be healthier in a world where being healthy is more challenging than it should be.

The five hormetic stressors you write about that you say are known to affect health are exposure to phytotoxins by eating plants, exercise, exposure to extreme hot and cold, periods of food scarcity, and psychological challenges. Are there other possible hormetic stressors or are those very well defined as the ones that are known to affect health?

These are some of the best studied, but there are others. For example, hypoxia can create enough stress to stimulate some cellular resilience. And there may be others. But the threat of starvation and the ability to expend energy in search of food were such dominant forces in shaping our gene expression. I think that plant-based foods, the timing of our meals, and our need for exercise are just so hardwired in our genes that those are going to be the biggest drivers. I focused on these because I wanted to think of lifestyle interventions that have the maximum impact in the least amount of time.

You connect hormesis to the way that discomfort has been sort of engineered out of our lives. Can you talk about that connection?

We often think about the mismatch between the radical changes introduced to our lifestyles since the industrial revolution and our genome. For example, the introduction of screens and how that has affected the amount of sedentary time we have and the way we think.

But there’s an even greater mismatch with what we have removed from our lives. For example, we have introduced food preservation technology and refrigeration, so we no longer have the need to go long periods without food. We have introduced indoor heating and air conditioning, which have removed exposure to extremes of heat and cold. We have introduced artificial light, which has removed us from the natural daylight and darkness that set our circadian rhythm. We have introduced technology that has removed the need for intense physical labor. With the introduction of these changes, we have removed physical, mental, and emotional stressors that activate our body’s natural ability to thrive and grow stronger.

It seems like there’s a bit of a tension in the book between the science you discuss and some popular wellness movements. For example, you write that you sometimes cringe when you come across “detox” regimens but that you’ve created “literally a detox program.” You also say you’re less interested in biohacking than in hormetic stress. Where’s the line between taking advantage of hormetic stressors and biohacking or a fad diet, for example?

A lot of these modalities — intermittent fasting, cold plunge, sauna — have entered the wellness world as either trends or as biohacks to increase longevity. What I hope to communicate first and foremost is that this isn’t just for people who want life extension or ultra health; these are for everybody. We now call them interventions, but these were once part of normal life.

This is really a call for a return to what is normal. The common thread is that we grow more resilient through these stressors and that is how we ultimately mitigate a lot of the harm that’s happening to us through our modern lifestyle. Our bodies are currently out of balance because we incur the harm, but we are not activating our innate ability to mitigate that damage — to repair, renew, and regenerate ourselves to stay in the homeostatic balance that our bodies need to maintain health and longevity.

The solutions you’re suggesting are pretty simple in some ways. When I think of fasting, I think of something extreme, whereas what you’re talking about with intermittent fasting is just limiting eating to a certain window in the day.

That’s such an important distinction. Hormesis is by definition a mild to moderate amount of stress for a brief duration followed by recovery. That is the pattern by which our bodies thrive from stress. Any one of these good stressors taken to an extreme can have an adverse effect. With exercise, we know that there’s a downside to overtraining. If a person is exposed to brief intervals of cold — like thirty seconds to five minutes of very cold exposure — that is a brief duration that activates our cellular stress responses. But chronic cold exposure can lead to hypothermia. If a person does time-restricted eating — eating in a window of 12 hours or less and having most of those calories earlier in the day — that is a normal pattern of eating. But if a person goes days without eating, that can lead to muscle breakdown.

For the purposes of hormesis, what is key is a mild to moderate amount. We know that there’s a limit to how much the body can improve its resilience from exposure to any one of these hormetic interventions.

How has your research in this area changed your day-to-day practice with patients?

I really encourage my patients to make just small incremental changes. One of the little things that I mention in the book is to add a few more plants to your diet. Only one out of ten Americans eats the recommended five fruits and vegetables a day. And we know that just doing that can reduce the risk of cancer by 50 percent. I encourage people to do short spurts of high intensity exercise — something as simple as running up a flight of stairs. It’s encouraging these little things that can make a difference — the 30 seconds of cold at the end of the shower, ending eating two to three hours before bedtime, stimulating yourself with some type of challenge that pushes you out of your comfort zone but is not overwhelming.

Because they seem so simple, sometimes it’s easy to discount how much they can add up. But in primary care, you have the fortune of watching your patients longitudinally over time. I’ve been in the same clinical practice for 25 years now, so I have watched my patients go through decades of their lifespan and seen the impact both short term as well as long term in their health when they incorporate some of these changes.

Are your patients receptive to this approach? How do you try to convince them of the potential benefits?

It’s not a tough sell if you explain what happens in the body if you do not change the current path. For example, 93 percent of people in this country have some level of metabolic disease. We know that metabolic disease starts with insulin resistance, and that train has several stops, including fatty liver, prediabetes, diabetes, cardiometabolic disease, neurodegenerative disease, and cancer. I can tell them the train they’re on, and most people don’t want to be on that train. But most physicians don’t tell people that this is the natural history if you either don’t make changes or if you rely on medications, which cannot get at the crux of reversing insulin resistance. When I explain to people that this is their future and if they want to be at a different point when they are grandparents, when they have finally retired, most people decide that that is not the path they want to be on.

So most of my patients are receptive. It’s more about explaining what they need to do. It’s challenging because there’s such limited time. But over numerous visits, I incorporate a little each visit. Over time, we change patterns and habits. I’ve created resources to help people. I’ve created courses that are at no cost just to help people get on a path that I hope gets them to a better endpoint. I give people ways to self-assess where they are.

I think it’s different from telling people to diet and exercise, which I think has been said so much and can mean so many different things that it’s lost its meaning. But when you introduce specific, evidence-based things you can do to change that path, it is really remarkable seeing how people respond to and appreciate that type of information.

Does the practice of medicine need to change in any way to incorporate this approach?

I think, wholeheartedly, yes. And I’ve spent a lot of time trying to find a pathway within the practice and scope of medicine where it’s accessible to everybody. There are numerous challenges, one being the allotted time in an office visit. Most of the time goes toward stamping out the fires, treating the problems that have arisen, and there’s very little time to really focus on the preventive piece. The second limitation is that everything I know about prevention, I’ve learned on my own. I think how we educate doctors doesn’t have enough focus on prevention.

I will say that our health system is miraculous in terms of treatment, and I in no way want to take away from all the incredible work that’s happening across the country at our institution and many others. But at the end of the day, we’re in an unsustainable trend toward development of chronic disease. It is just cost-prohibitive. We need to have some creativity and reinvention so that we can bend the cost curve — not by denying treatment and access, but by making people healthier where cost-reduction is a byproduct and not the primary outcome. That’s my vision. There’s still a lot of work to do.

Lifestyle medicine seems to be growing pretty quickly. Do you see more acceptance of these concepts among colleagues in medicine, even those who are not working in lifestyle medicine?

I think there is. When I introduced the idea of lifestyle medicine in our center about fifteen years ago, it was not well understood or received. The comment that was frequently made was, “She prescribes broccoli.” As the understanding of how powerful lifestyle is and that 80 percent of chronic disease can be prevented with lifestyle — and how gratifying it is for practitioners to help people become healthier, potentially reducing burnout in health care — all these factors have driven interest in lifestyle medicine. I’m a member of the American College of Lifestyle Medicine, which is now a subspecialty in which one can be board-certified. So I think there is more interest and attention, and I hope that it gets to a tipping point where this is the language that we speak and more people feel comfortable prescribing broccoli.

Do you think part of the problem with acceptance is that there’s this association with the wellness industry, with influencers, that might make people who are scientifically minded a little skeptical?

Yes, I think that’s a good point. There’s widespread disease and widespread confusion, so it’s an interesting era. If you only prescribe broccoli, I do think it’s very hard to differentiate from wellness trends. And now everyone is an expert. Having academic credentials is almost a liability.

So I understand some of the skepticism, but I also feel like academic centers should be leaders. We should be leading an evidence-based lifestyle. If we don’t step up, we’ve created this gap that’s getting filled by influencers. I think that is a gap that we have to bridge. We have to lead this movement. Otherwise, patients resort to questionable information and an entire industry of unproven supplements and gadgets that are just not adequately tested. I just really hope that we have an evidence-based middle ground here of lifestyle as medicine that helps redirect a lot of the wellness trends.

It’s important to acknowledge that I value so much of the innovation in the health system. The advances in cancer therapeutics, for example, are incredible. I have such respect and appreciation for every person in the system who is offering these procedures and treatments. But I also feel like we just have to balance it with an emphasis on prevention. The knowledge is there; we just haven’t implemented it. This is medicine hidden in plain sight.