The director of the Institute for Behavioral Medicine Research at the Ohio State University College of Medicine in Columbus, Dr. Kiecolt-Glaser has authored more than 250 articles, chapters, and books on subjects related to psychoneuroimmunology, many with her late virologist husband, M. Ronald Glaser, PhD. The pair spent three decades focusing on the link between chronic stress — the kind endured by many family caregivers‚ and poor wound healing, greater infectious illness susceptibility, increased allergy symptoms, and other illnesses and conditions. Then, Dr. Ronald Glaser received his own dire diagnosis. He was told that he had early Alzheimer’s disease, and the illness quickly progressed. Ronald Glaser passed away on April 3, 2019, after spending many months in an Alzheimer’s unit receiving round-the-clock care, while Janice Kiecolt-Glaser continued soloing, with a focus on the effects of stress on the immune system. Her current studies explore the ways in which marital strife, stress, and depression affect the gut microbiome (the microbes that live in your digestive system) and metabolism; topics that hit remarkably close to home. She spoke with Everyday Health about her research, her struggles, and her future. Everyday Health: Many of us know that chronic stress affects our eating habits. But how does stress affect metabolism? Janice Kiecolt-Glaser: In several meal challenge studies we watched what happens metabolically after our subjects consumed a high-fat, fast-food-type meal. We discovered that people dealing with recent stressful events burned fewer calories and had elevated insulin levels after these meals when compared with those reporting little or no stress. We believe that this combination of reduced calorie burn and heightened insulin creates the perfect recipe for weight gain and fat deposition. This was surprising. We didn’t think stress would yield this kind of result. EH: What does this finding mean in terms of the average person’s health?   JK-G: It helps explain why it’s so hard to lose weight. When people are stressed, they seem to burn fewer calories. They also sleep poorly and they may have a dysregulated circadian cycle. These factors may contribute to increased hunger and, worse, cravings for high-calorie snacks. Apparently, humans have drastically changed lifestyles and eating habits too quickly for the body to have evolved accordingly. In the past, every animal faced a similar “eat or be eaten” situation. But today’s chronic stress has nothing to do with being consumed by another creature. We’re consuming ourselves with worry and anxiety. EH: What has your research revealed about the link between the stress of a troubled relationship and the microbiome? JK-G: We’re in the early days of figuring this out. The healthy intestine has a layer of cells that act as gatekeepers putting gut-manufactured nutrients into circulation and keeping harmful bacteria sequestered. The prolonged damage that occurs with chronic stress, especially when combined with the high saturated fat of “comfort foods,” can weaken the gut’s lining, rendering it more permeable. Illnesses and antibiotics can have the same effect. But you can see how it makes sense that stressful marriages can create leakier guts, triggering an inflammatory response that contributes to many inflammation-related diseases and disorders. Those include cardiovascular disease, type 2 diabetes, depression, frailty, and functional decline. EH: And yet we hear that couples enjoy greater longevity than singles, right? JK-G: We know that marriage increases longevity for men in part because women tend to convince male partners to seek care. More broadly, we and others have shown that happy couples enjoy lower levels of the inflammation associated with many chronic diseases of aging. On the other hand, bad marriages are a major source of strain. I’d like to study those relationships for their effect on aging. Researchers are starting to examine the relationship between this stress and biological measures such as telomere length — telomeres being the caps at the end of each DNA strand that protect our chromosomes from becoming damaged. The length of your telomeres is a measure of your biological age, as against your chronological age. EH: Every new finding seems to underline the power of the gut microbiome, or our gut bugs. Just how far does its influence reach? JK-G: To underline the effect of the microbiome on people’s mood and psychology, you need to see the lovely work from John R. Kelly of University College, Cork, Ireland, and his colleagues. They demonstrated that fecal transplants from depressed people induced behavioral and physiological features of depression when they were introduced into microbiota-deficient (germ-free) rats. The rats that received the depressed microbiomes displayed the characteristic lack of interest and motivation, as well as the anxiety, associated with depression. The experiment suggests that depression can be transferred, but also that the “right” bacteria may be capable of having a positive effect on depression when transferred to the right recipient. There’s also some evidence that people who have been together and intimate for years seem to develop similar microbiomes. They’re typically on the same diet, in the same environment, with the same pets and children. This is a particular area of interest of mine. EH: How can we address these chronic-stress-related metabolic problems? JK-G: The ideal solution is to manage stress more efficiently. Certainly, mindful eating is a wonderful way to keep a better handle on what’s going on with weight and metabolism. But obesity is pretty rampant in the United States and across the world. And we are at a very stressful time in our history. You would hope that other kinds of interventions would also be part of someone’s stress-reduction program. We had a 2014 randomized controlled trial that showed that yoga lowered inflammation through its effect on inflammation, mood, and fatigue in breast cancer survivors. And there are several studies from other groups demonstrating how mindfulness meditation can also lower inflammation. In addition, it’s well known that exercise can lower inflammation. All of these contribute to a healthier life. On the other hand, people who are stressed eat poorly, exercise less, drink more, and smoke more; all of which contributes to further chronic stress. Sadly, small periods of being sedentary can erase the gains made through exercise, as one example. EH: How difficult is it to get an accurate read on an individual’s stress level, given how poorly many are sensitized to and understand their own emotions? JK-G: We need to get back in tune with ourselves to understand and pay attention to potential danger signs. We also have to understand that signs of misinterpreted stress vary across people. Some people get headaches, some get stomach problems, some see changes in their behavior, as when they suddenly find themselves foraging for donuts in the morning. And everyone has to watch for when and how we self-isolate. With chronic stress, people tend to distance themselves from others at the very time they need connections. Keep an eye on the social calendar. If we’re not scheduling as much time with friends and family as before, it’s a sign that other things may be going on and going wrong. EH: What about the very particular, and intense, effects that chronic stress might have on caregivers in terms of illness? JK-G: Caregiving is very stressful. My husband and I spent years studying caregivers as a means of examining the health consequences of chronic stress. Alzheimer’s and dementia create some of life’s most difficult and most uncontrollable chronic stressors; situations where you don’t know what’s going to happen next, where you have little influence on or control of symptoms, and where there’s no control over the disease’s progression. There’s also the profound grief that comes with watching someone you love disappear. I was in this situation myself. My husband and I did some of the original work showing that caregivers have poor vaccine responses. Their wounds are slower to heal, and their inflammation is heightened when they are compared with their noncaregiving age mates. EH: What was your husband’s situation? JK-G: In 2014, he was diagnosed with early Alzheimer’s. I hired people to help provide care while I was at work, but two years ago it became too difficult to manage him at home, even with help. I was able to move him to an excellent Alzheimer’s unit. He deteriorated to the point where he’d been under hospice care for 16 months before he passed away on April 3, 2019. We’d had a very good marriage. Near the end, he occasionally recognized me, but I was never sure. The body was there. The man was gone. EH: How do you ensure that you care for yourself? JK-G: When I knew what we’d likely encounter, I worked hard on my friendships. Caregivers can easily lose their social network and they’re often afraid to bring people to the house because they don’t know how their family member will behave. At the same time, it can be very difficult to get out when you’re constantly providing care. I also made sure to exercise and started practicing mindfulness meditation. There’s nothing that can eliminate the sting, but I have friends and my work to turn to. I’m deeply grateful for that. EH: Based on your own experiences, how can we prepare for and anticipate caregiving demands, both as individuals and as a society? JK-G: We can start by ensuring there’s good respite care for caregivers. I remember one of our study subjects, a retired former engineer who took a part-time job at a local hardware store. His salary didn’t even begin to cover his wife’s day-care costs, but he enjoyed the public contact and the sense of helping others. It was worth it for him, as it would be for almost anyone. Without a break, intense and ongoing caregiving is a recipe for depression. As a society, we need to provide broader help. Caregiving is an unrelenting strain for those with no alternative. As individuals, we need to defeat chronic stress by first recognizing it; paying attention to its effects on the body. We have to give more credence to alternative practices — yoga, meditation, body awareness, tai chi, and the like — to cultivate calmness and control. EH: What is your next research challenge? JK-G: The next study, which we are trying to finish now, looks at how chronic stress may have altered metabolism during a two-year breast cancer treatment period. It’s too soon to have a sense of the findings.

Dr  Janice Kiecolt Glaser  Q A on Stress s Link to Metabolism  Marriage  and Caregiving - 35