21-05-2025
Episode 4: Lupus and Lifestyle: What Patients Can Control
This transcript has been edited for clarity. For more episodes, download the Medscape app or subscribe to the podcast on Apple Podcasts, Spotify, or your preferred podcast provider.
Maureen McMahon, MD, MS: Hello, I'm Dr Maureen McMahon. Welcome to the Medscape InDiscussion podcast series on systemic lupus erythematosus. Today, we'll discuss environmental exposure in lupus with our guest, Dr Karen Costenbader. Dr Costenbader is a professor of medicine at Harvard Medical School and holds the Michael E. Weinblatt MD Distinguished Chair in clinical rheumatology at Brigham and Women's Hospital, where she serves as the director of the lupus program.
She specializes in treating systemic lupus erythematosus and related connective tissue diseases.
Karen Costenbader, MD, MPH: Hi, Maureen. It's very nice to be here. Thanks.
McMahon: I'm excited to talk about this with you. Of the questions that I get from my lupus patients, these topics are at the top of the list of things that people want to know about. I'm excited to hear what you can tell us today. I know you've done a lot of research in this area.
Costenbader: I think it's a fascinating topic as well.
McMahon: The top thing that I get asked about, concerning how patients got their lupus in the first place and how they should manage their lupus, is around the topic of diet. I know that you've done some research on different food exposures, and I was wondering if you could talk to us about that.
Costenbader: To back up, I've been looking for why people get lupus and environmental exposures for most of my career. I think it's such a complex disease. There's so much going on in the immune system. We know that people develop lupus because they probably have a genetic predisposition.
But then, along the way, there are environmental factors, including everything you can think of in life that might be environmental, or even behavioral and lifestyle, and all these other things, like diet, that we're exposed to that could increase or decrease our risk of developing lupus.
And then those factors can interact with each other. It may not just be one exposure; it could be multiple things. It's been complicated to study, but I've been lucky to have access to the Nurses' Health Study, which is a very large cohort of women, started back in 1976 here at the Brigham Women's Hospital in Boston.
We've also studied diet and the risk of lupus in the Black Women's health study, which is based at Boston University. We are not the only ones studying diet in the Nurses' Health Study and Black Women's Health Study in other cohorts. A lot of the world's greatest researchers in nutritional epidemiology work in these cohorts and have developed different algorithms for looking at diet and putting all these foods into different patterns.
We've looked at Western and prudent diets and the risk, and a lot of this we've done for rheumatoid arthritis as well, which is more common. In the rheumatoid arthritis analyses, we have a larger sample size and more power. And then we look for lupus, which has a smaller sample size. As you said, everybody is interested in diet.
What are we taking in that might change our immune system, that might increase or decrease the immune stimulation of someone who might be developing lupus or another disease? We looked at Western and prudent diet, and we didn't see anything for the risk of lupus.
We looked at several different dietary patterns that were already put together, including the DASH (Dietary Approaches to Stop Hypertension) diet to reduce hypertension, as well as the Alternative Healthy Eating Index (AHEI), a Mediterranean dietary pattern, and an empirical, pro-inflammatory diet, which was based on biomarkers. At that point, we didn't see much risk related to diet. We saw, maybe, that nuts and legumes were associated with a lower risk; the same is possibly true when reducing carbohydrates. In the Black Women's Health Study, we looked at Western and prudent diets, and then we looked at many different dietary and nutritional components. We saw that high carbohydrate intake was associated with an increased risk of developing lupus later on. The Black Women's Health Study started in 1995 and followed women forward with similar questionnaires.
It was based very closely on the nurses' health study pattern. It's been easy for us to translate our work over there, asking women every couple of years about their dietary intakes over time. And then we have also gotten medical records and validated the new cases. And so, here we saw especially high intake of carbohydrates.
And then most recently, we've been interested in what people are ingesting through their diet for a long time. For example, junk food, ultra-processed food. The categories of ultra-processed food were defined by Professor Carlos Monteiro in Brazil a few years ago. He categorizes foods into these four categories, where ultra-processed is the most processed.
And then we had to adapt them for the nurses' health study. It puts food into categories. The lowest is raw. You eat an apple, that's unprocessed. You know where it came from, what it is, et cetera.
And then there are two intermediate categories of semi-processed and then processed, which is like eating applesauce probably out of a can. It depends on what else is in it. Ultra-processed is something that only vaguely resembles food anymore. It's like a lot of chips and soda. It doesn't have a lot of nutritional components. It has a lot of other stuff in it, including emulsifier and stabilizers, and other stuff that they put in, like dyes and things that are hopefully regulated. We don't know if they're harmful to human health.
And there is a lot of high fructose corn syrup, especially in sodas and things. There, we did see an increase in the risk of developing lupus many years later. When we did this in many ways, in terms of cumulatively updating from the beginning and putting people into tertiles of the highest intake of ultra-processed food, the real junk food, there was a clear signal of an increased risk. And then in many of these analyses, we have done stratified analyses by double-stranded DNA positivity from the medical records at the time of diagnosis. We don't follow the women and the studies after their diagnosis. That's a little too hard.
But at least we get all the medical records at the time of diagnosis. About 50% of patients tested are positive. We saw a stronger signal with double-strand DNA positivity, which is always good to see because, in my opinion, that's real lupus, you know?
We know that that's highly specific for lupus, and it's about a doubling of risk. It was about a 50% increased risk overall in the highest tertile. So that's a real signal. After looking at the data multiple ways over multiple years, I think we now see that it's the bad food. The ultra-processed food may be contributing to the risk rather than these other patterns. And these are all calorie-adjusted. Taking in a lot of this food. We looked at absolute intake as well as relative intake. And it looked like it was the absolute intake in terms of grams per day, or servings per day, rather than the percent of the dietary intake. It's really how much exposure you have.
McMahon: How are you counseling your patients when it comes to diet? They're your patients; they've already developed lupus.
Costenbader: I think we can still recommend a healthy diet, avoidance of ultra-processed food. When we looked at all the different kinds of ultra-processed food, of course, we didn't have the power to look in every single category, but we did anyhow. And we saw that it was soft drinks, soda, both artificially sweetened and sugar sweetened, that had the strongest signal.
So, I think if you're going to change one thing about your diet that really might be pro-inflammatory and has a lot of high fructose corn syrup and probably a lot of excess carbohydrate as well, is to stop the soda. We also know it's bad for kidney disease and a lot of other things. I think that we can counsel our patients about ultra-processed foods for a variety of reasons.
This includes rheumatology patients and all patients in general, because the high intake of ultra-processed foods has been associated with risk of all-cause mortality, cancer, cardiovascular disease, diabetes, hypertension, you name it. And we take in a ton of them.
When I was doing research for this paper, we looked at data from NHANES (National Health and Nutrition Examination Survey), from I think 2011 to 2017, that found that for adults in the US, about 50% or more of the diet in terms of calories comes from ultra-processed food. It's gone up in every category of people. When they did stratified analysis, it's going up even faster, above 60%, almost 70% of the diet comes from ultra-processed food in people with less than a high school education. There's a clear gradient. It's still going up, but it's much lower in people with a college education.
And then the other category that really surprised me is older people. It's very high in older people, and I think maybe they just don't have access to healthy foods and maybe are eating many more processed and prepared foods.
McMahon: That's really helpful to know and helpful to have that conversation with patients, because it is sometimes easy to follow the path of least resistance and get the easily prepared ultra-processed foods. One of the other things that comes up frequently when patients are asking about how they developed their lupus in the first place, is that maybe they had an infection that preceded it, that they're linking to it.
And I was wondering what you know about the data that confirms or denies that.
Costenbader: It's much harder to study infections and whether they trigger the onset of lupus or other diseases; I think there've been a lot of glimmers that they probably do.
Because, as you can imagine, there are a lot of good reasons to think that infections, and maybe it's not just one type of infections, have an effect. We learned during COVID that they trigger cytokine storms, that there's lots of inflammation going on. There have been several studies now using large populations and administrative data that do show that the risk of developing all kinds of autoimmune disease.
McMahon: One of the other things I have to ask you about is the role of vaccinations and what you know about vaccinations triggering or worsening ongoing disease.
Costenbader: So, I'll start off with a disclaimer that I'm a big fan of vaccinations. Some people should not get vaccinated, if they've had bad reactions in the past or if they have Guillain-Barre is something autoimmune that is triggered by vaccinations.
I don't think we have such evidence for lupus. It is hard to study because, in the past few years, we've all been getting a lot of vaccinations for COVID. I think in general those vaccinations have saved so many lives that the risk benefit is heavily in favor of the benefit.
And definitely for people with lupus, I'm a big proponent of getting all the vaccinations because they are immunosuppressed, and vaccinations save lives. It's not been well studied, but there are some signals that some of the COVID vaccinations were associated with pericarditis in younger people especially. I don't think that we have a signal for lupus or other autoimmune diseases that is as strong as having the disease itself. And other vaccinations as well have been a little bit investigated over the years, but I've never seen any strong evidence that having vaccinations was associated with the onset of lupus.
McMahon: Great. Thank you. What about other environmental exposures. things like air pollution or chemical exposures? What do we know about those?
Costenbader: There's more and more data on those, too. Smoking is a risk factor for lupus, as it is for rheumatoid arthritis. And we've seen that smoking increases the risk by about 50%, especially for current smokers. And then the risk dissipates over time, and that also is more strongly [associated] with doublet stranded DNA positivity.
It is probably auto-antibody generation, at least that was my hypothesis, because it does the same thing in generation of anti-CCP (anti-cyclic citrullinated peptide) positivity in rheumatoid arthritis. I think from there we started thinking much more about other inhaled exposures and air pollution. There are several nice studies. We had looked at air pollution many years ago, it was one of my first grants actually. We looked at the risk of lupus and RA in the Nurses' Health Study. We probably didn't have the power at that point. We did see a signal for rheumatoid arthritis, but not for lupus. But there are other studies. I know Sasha Bernatsky in Canada has studied air pollution and risk of systemic autoimmune rheumatic diseases in general, including lupus. There is an increased risk.
More recently, there has been work on fire and air pollution in rheumatoid arthritis. It wouldn't surprise me at all if it's similar in lupus. And then in terms of pesticides, I think some of the nicest work has been done by Christine Parks and the Agricultural Health Study.
She gets into all the different types of chemical fertilizers, pesticide exposures, and insecticides. I can't tell you all the different types, but she does know all the different types and she's looked at mixing the pesticides and applying the pesticides, and being a spouse of the farmers who are as so associated with them. And here there is a risk as well.
We went back in the Roxbury lupus study, which was a case-control study in urban Boston neighborhoods several years ago, and the women had answered questions about pesticide exposure. There it was rodent and roach insecticide applications in the home that people were exposed to.
We saw a risk associated with that as well. I think there are a lot of chemical exposures out there, like organic solvents and pesticides, that people are exposed to that could stimulate the immune system. We don't understand all the mechanisms, if these are similar mechanisms or if they're a different mechanism.
McMahon: What about some of the other lifestyle things? We talked a little bit about smoking, but what about other things like sleep or stress?
Costenbader: We've studied those as well. I think that's the beauty of the Nurses' Health Study too. These are kinds of exposures have been self-reported for many years. We can look back many years before, we saw that sleep deprivation, as you mentioned, was associated with increased risk, a very strong increased risk, about two and a half times higher risk.
In our study, the chronic low sleep deprivation duration category was less than 5 hours a night vs less than or equal to 5 hours a night vs greater than 7-8 hours, which is considered normal. But everybody's different. My boss, for example, only needs 4 hours of sleep at night, and it's very annoying.
Some people can get away with it forever and function very well. Some people will say, I always get 10 hours of sleep, which is very lucky with them as well.
You mentioned stress and psychosocial factors. PTSD has been strongly associated with the risk of lupus and other autoimmune diseases, and trauma exposure, depression, and adverse childhood experiences as well. We've seen the same with RA and with lupus. We've tried to do kind of a mediation analysis as well because it's hard to know what's going on. There are studies that show having PTSD is associated with having more systemic inflammation, so having higher CRP and IL-6 levels, interestingly. But is this through unhealthy lifestyle as well? Is it more smoking and less exercise and more obesity, and is it a lot of other things? Part of the associated risk is mediated by that, but there are also maybe direct impact. We wrote a whole review on how PTSD may be related to lupus, and there are a lot of things beyond other risk factors.
We found the HPA (hypothalamic-pituitary-adrenal) axis being invoked, and vagal tone could be a part of it. People are very interested in the stimulation of the vagus now, which could be good in terms of increased awareness. And the parasympathetic nervous system is good for reducing inflammation and calming. I think that's all fascinating.
McMahon: I think that's a hopeful message. Because I think it is nice for patients out there to think that there are things that they can control. There are so many things that we're out of control in our lives, but controlling your healthy lifestyle and focusing on eating well and exercising, I think that that's a good message for all of us.
Well, thank you so much, Karen, for talking to us today. Today, we talked to Dr Karen Costenbader about environmental exposures in lupus. We've all learned about risk factors, but also how healthy lifestyle habits can hopefully lead to better outcomes and healthier patients all around.
Thank you for joining us, everyone. Please take a moment to download the Medscape app to listen and subscribe to this podcast series on systemic lupus erythematosus. This is Dr Maureen McMahon for the Medscape InDiscussion podcast.
Systemic Lupus Erythematosus (SLE)
Risk Prediction Models for Incident Systemic Lupus Erythematosus Among Women in the Nurses' Health Study Cohorts Using Genetics, Family History, and Lifestyle and Environmental Factors
Association of Macronutrients and Dietary Patterns With Risk of Systemic Lupus Erythematosus in the Black Women's Health Study
Dietary Patterns and Risk of Systemic Lupus Erythematosus in Women
Alternative Dietary Indices Both Strongly Predict Risk of Chronic Disease
Ultra-Processed Foods: What They Are and How to Identify Them
Anti-dsDNA Antibodies in the Classification Criteria of Systemic Lupus Erythematosus
Identifying and Estimating Ultraprocessed Food Intake in the US NHANES According to the Nova Classification System of Food Processing
Development of a Predictive Model for Systemic Lupus Erythematosus Incidence Risk Based on Environmental Exposure Factors
Systemic Autoimmune Rheumatic Diseases and Multiple Industrial Air Pollutant Emissions: A Large General Population Canadian Cohort Analysis
Pesticide Exposure and Risk of Rheumatoid Arthritis Among Licensed Male Pesticide Applicators in the Agricultural Health Study
Pesticide Exposure and Risk of Systemic Lupus Erythematosus in an Urban Population of Predominantly African-American Women
Association of Sleep Deprivation and the Risk of Developing Systemic Lupus Erythematosus Among Women
