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    MIND Diet, Lifestyle, and MS

    This transcript has been edited for clarity.

    Anne Cross, MD: Hello. I am Dr Anne Cross and welcome to Medscape’s InDiscussion series on multiple sclerosis (MS). Diet and lifestyle factors appear to be involved in risk of developing MS, and studies indicate that risk of MS is increased by genetic susceptibility and by environmental factors, of which diet and lifestyle may play large roles. Notably, MS is more frequent in first-world countries, where the typical diet is high in saturated fats and sugars, and in calories compared to the diet of people in “third-world” countries, where MS is less common. Many people with MS are very interested in dietary and lifestyle changes that might improve their symptoms or prognosis. A survey a few years ago found that 91% of respondents were interested in diets that might help manage their MS. I’d like to introduce Dr Ilana Katz Sand, who is an associate professor of neurology at the Icahn School of Medicine at Mount Sinai Hospital in Manhattan. In addition, she is associate director of the Corinne Goldsmith Dickinson Center for MS and co-director of the C. Olsten Patient Wellness Program at Mount Sinai Hospital. One of Dr Katz Sand’s main research interests is the role of specific diets and dietary components in relationship to MS outcomes, and that’s going to be the topic of most of our discussion today. But first, Dr Katz Sand, please tell us a bit about yourself. Why did you choose medicine and the field of neurology to study and what led you to MS as a particular field of neurology?

    Ilana Katz Sand, MD: Thank you so much for having me. It’s exciting to be here today. In terms of my background and how I got here, thinking about career options way back when, I wanted to do something that I felt was important and where I was motivated to come to work every day and be able to make a difference. My father happens to be a neurologist, and so I had the wonderful opportunity to hang out with him when I was a kid, before there were all the rules and regulations we have now. I used to just go with him into the hospital on weekends to see patients. I loved that intersection between science and having the opportunity to make a difference in people’s lives. That was how I got into medicine. Of course, I had that background in neurology, and so I was always interested in it from hanging out with my dad. But I think more broadly, the brain controls everything, right? I found neurology fascinating for that reason. I was one of those people who went through medical school and loved almost every specialty that I rotated through and thought each time, Oh, this maybe this is it … I love this! I had a really hard time deciding, but at the end of the day, I just kept coming back to neurology. I think it’s such a fascinating field. And then as I went through my residency, again, I thought all the subspecialties were interesting, and I think I probably would have been happy doing any one of them. But I just was drawn to MS because a lot of the patients are women and I looked around me and saw you, Dr Cross, as the exception … most of the people I was looking at when I was training were men. I thought, I relate well to this patient population, and I think I can be useful here in terms of shared experiences. And I loved the idea of getting to have long-term relationships with people. And so that was something I was really interested in. And then I really loved how the field was changing so much. It was important to me to be able to feel like I was able to do something for people. It was a wonderful time, right when I was coming into my fellowship in 2011, when the field was really changing a lot and we were making great progress in terms of treatments and what we can do for people. It seemed like an exciting place to be from a clinical standpoint, but also from a research standpoint. It was a field that there’s still so much more to do and where I felt like I could be useful, and I’d be able to contribute going forward.

    Cross: That’s great. I, for one, am very happy that you chose neurology and MS, and I’m sure your patients are happy too. Dr Katz Sand has recently completed and published a two-center study of diets in MS; it’s an observational study, and I’m wondering if you could tell us a little bit about that study. It had some intriguing results that you might want to share with us, and I believe you have had a second publication on that come out today that you can share with us as well.

    Katz Sand: I’ll tell you a little bit about some of the work that we’ve done. When I was a fellow, one of the things that really struck me was how little evidence we had about diet. I immediately noticed, as all of us clinicians do, that this is something that so many of our patients ask about during the clinical visits. But when I asked my mentors about it and looked in the literature, I found that there really wasn’t a lot to guide us. At the same time, I observed my patients who seemed to be really committed to good overall health, and they seemed to be doing better from a disability standpoint. I just thought there must be something here. What I wanted to do at the beginning was just go for it and start running interventional studies. But of course, that was jumping the gun, and people quickly told me. I got very deserved feedback saying “You don’t have preliminary data for this on efficacy from a feasibility standpoint. If this is even going to work, how are you going to be able to run these kinds of clinical trials?” And so I said, okay, we have to do this in a stepwise fashion and figure out a more measured approach. So that was how we decided to run our first small pilot study. In that study, which we published in 2019, we randomly assigned 36 women with MS either to follow or not follow a modified Mediterranean dietary intervention. The study went great. What we were looking at there was clinical trial feasibility — we weren’t sure that we’d be able to recruit our target, which was to get 30 patients in a single center in 1 year. We were able to get to 36 within 9 months, so we stopped recruiting. We were really excited about that. The other things we were looking at were adherence. We were looking for a target of about 80% self-reported adherence and we actually hit about 94%. Things went really well from that standpoint. Almost everyone in the study completed it, except for one person who kind of went missing and one who unfortunately moved in the middle of the study. Otherwise, people were excited about it. They were able to follow the program for 6 months. And so we thought, okay, we can do this. So then we wanted to look at how can we get some data again with the goal of eventually getting toward big clinical trials. How can we get data about diet as a disease modifier? We have to do observational studies. And so that’s where the RADIEMS paper comes in. That was the first piece of work that we did. The RADIEMS cohort — RADIEMS stands for Reserve Against Disability in Early MS — is a really wonderful cohort that is run by my colleague Dr Jim Sumowski, who is an MS neuropsychologist. We’ve been so fortunate to have him here at our center for a number of years now. It’s an NIH-funded cohort. We enrolled 185 people in 2016 and 2017 into the study. They were all within 5 years of MS diagnosis. These are young people — average age in the study at enrollment was 34 years and the average time for diagnosis was about 2 years. The median Expanded Disability Status Scale (EDSS) was zero. It’s when people were early on so we couldn’t really look at clinical outcomes in that group at baseline. But what we could do was look at imaging. And so, what we did was have everyone complete a food frequency questionnaire when they entered the study at baseline. That was a really extensive dietary inventory from which we can calculate where people fall out on different patterns. And so we applied a score, which is called a MIND score; MIND is Mediterranean DASH Intervention for Neurodegenerative Delay. The idea was for it to be a Mediterranean pattern, but with specific callouts for items that they think are of particular importance for people who have neurodegenerative diseases based on preclinical literature … so purely observational data and their MRIs. And what I think is the most interesting finding from that paper was that we found a link between the MIND score and thalamic volume. Of course, we don’t expect to see widespread atrophy and overall decreased volumes. That’s something that comes later when you think about people who are in their thirties who don’t have MS, right? It’s very different. This is something that we think is a pathologic finding. And so, the fact that we were able to see that association in people so early in the disease was interesting to us. Getting to the paper that we’re really excited about published today in MSJ (Multiple Sclerosis Journal) that’s now online, there we wanted to look clinically at outcomes, which we couldn’t do in RADIEMS. What we did was look at our comprehensive annual assessment cohort. We’re very fortunate here, because beginning in late 2018, we started a program through our neuropsychology clinic, which Dr Sumowski directs, and we now run this comprehensive annual assessment. We have the patients fill out a bunch of different patient-reported outcomes … questionnaires. They fill out a dietary screener, which is the MEDAS, the Mediterranean Diet Adherence Screener; it’s 14 questions and people get assigned a score, and they also fill out questionnaires about fatigue and mood, all kinds of things. And then they come in person and do an assessment where we do a nine-hole peg test, an SDMT [Symbol Digit Modalities Test], and a timed 25-foot walk test, and a bunch of other assessments that we do through that clinic. It’s a great resource for patients and we will be using this cohort longitudinally for research, too. But here, we just looked at the baseline data, and the primary outcome was to see whether there was a link between their MEDAS score, the Mediterranean scale, and the Multiple Sclerosis Functional Composite (MSFC) score. And the wonderful thing about this cohort is that they are our patients and we asked them a lot of questions. And so, unlike in a lot of other dietary studies, we were able to control nicely for a lot of confounders. That’s a big problem with observational studies of diet — these behaviors are all linked. And so here we were actually able to rigorously control for demographic factors. We put together a very nice socioeconomic status index that looked not only at IQ (essentially, literacy) but also at parental education levels. That’s folded in there. And then we looked at a broad range of health-related factors, too. We looked at diabetes, hypertension, high cholesterol, BMI; we even looked at sleep. After really rigorously controlling for all of the exercise, all of those factors, we were still able to see a pretty robust association between how people score on that dietary scale and their MSFC. So, we were excited about that, and we also found associations with a whole bunch of patient-reported outcomes that we reported in the paper. That brings us up to date to now.

    Cross: I will just reiterate that this paper came out on October 13, 2022, in Multiple Sclerosis Journal if our listeners want to look it up. Was there any specific component of the MS functional composite, the MSFC, that was associated with higher MEDAS scores or…?

    Katz Sand: Yes, all three components. More so with the nine-hole peg test and the SDMT, but also the timed 25-foot walk test. The association there was smaller, but yes, the individual components all had those associations.

    Cross: And would you mind elaborating a little bit on the modified Mediterranean diet that you mentioned versus the MIND diet? Are there differences between those two?

    Katz Sand: Yeah, it’s a good question. Not really … we called it a modified Mediterranean diet because when people hear “Mediterranean diet,” Mediterranean can mean so many things to different people. We call it modified in that we made our own adjustments and rules for it. What we did there was emphasize the components that you get points for when you do a MIND score. Because we were running a pilot study, we decided to make it a little cleaner. We decided that rather than de-emphasizing certain components, we were going to eliminate them because it was a pilot study and it’s easier to do things that way, and then consider adding pieces back later. We eliminated meat in that study, and we also eliminated dairy from that study. When we ran the pilot, those two things were out, and that helped us really emphasize things that are emphasized in the MIND score. Things like fresh fruits and vegetables. We told people, if you’re going to eat grains, they need to be whole grains. We emphasized fish, nuts …, really, most of the things that you get high scores for in MIND. You lose points in MIND for things like baked goods and butter, which are out when you eliminate dairy.

    Cross: And when you say you eliminated meat, do you mean all meat, like chicken and turkey also, or just red meat?

    Katz Sand: We did for that study because we thought it was going to be too difficult. There were still questions that came up, such as: “Well, is meat okay if it’s grass fed or is it okay if it’s chicken and it’s without antibiotics?” And we said, you know what, this is too nuanced. For the pilot, we’re just going to make it as clean and as easy as possible. We’re taking it all out. And we really want to get people to up their intake of these other foods, and that will help us accomplish that. We took it out entirely. I think for future trials, we’re going to focus more on the overall score and less on these individual components. I think it’ll be less about eliminating one thing or another entirely and more about the overall pattern, which is what we encouraged in the pilot, too.

    Cross: And so a big question … you may not know the answer to this, but I suspect you are working on it. What is the mechanism of action that might be going on here?

    Katz Sand: Definitely working on it. So, for the RADIEMS study, for example, we collected samples from everyone at year 3 and we’re processing those now. We actually got data back recently on metabolomics, which our collaborator, Dr Kate Fitzgerald at Hopkins, is working on as we speak. We collected stool samples from people. We have a collaborator here at Sinai, Dr Jose Clemente, who’s helping us do those analyses. We’re looking at all of this. We have a new project that Dr Sumowski and I just put in with Dr Jen Graves at UCSD, where we’re really interested in thinking about biological aging as a potential mediator of some of these effects that we’re seeing. But I would say overall, broadly speaking, you can think about direct effects of dietary metabolites and then you can think about indirect effects that are mediated through gut microbiota, for example. In terms of direct effects, everything we eat has a chemical structure, just like our pharmaceuticals. And these different dietary metabolites can have direct effects on cells in the gut. They also diffuse widely through the peripheral circulation. They bind to receptors on metabolic organs and immune cells and foods that give you points on a MIND score. They’re going to be high in fiber. They’re going to be high in antioxidants. We already know that Mediterranean patterns have been shown to have beneficial effects, not specifically in MS populations, but in the general population. This has been studied in terms of the gut microbiota, and the composition and function of the microbiota are heavily influenced by diet. So which bacteria are present and which metabolites they produce — which in turn is going to have effects on the local immune system in the gut and then in a lot of distant effects — are really determined in large part by the diet. We think there are probably multiple contributory mechanisms, and we’re going to study them all.

    Cross: Thank you. Another topic I was hoping we could touch upon is lifestyle and lifestyle factors. Have you studied this?

    Katz Sand: Yes. Especially from a clinical standpoint, we’re really interested in comprehensive care in MS. And we think that it should include not only all of the work that we all do talking to people about their disease-modifying therapies [DMT] and watching their MRIs and watching their labs, but actually looking at our patients as whole people and being thoughtful about lifestyle. I think there are a lot of factors that can make a big difference for people. We know that if we have two different patients who start in the same place and we put them on the same DMT, one of them may do great and the other might not. And so, we really must be thinking about what the modifiable factors are and where we can intervene and have an important influence on prognosis in our patients. Here at our center, we’ve been fortunate to be able to start a patient wellness program, which we launched about 2 years ago, right at the beginning of the pandemic. We’ve been working hard on this program over the last 2 years and will continue to do so. When people come into our wellness program, they meet with our nurse practitioner, with the dietitian, with the physical therapist, and with the social worker to really try to get a holistic view and recommendations coming at things from multiple spheres. You know, we just have so much work to do in this area. But of course, I think the only way forward with all of these things is to really rigorously demonstrate that through proper clinical trials, because that’s the way things actually move, right? That’s the way we get clinicians to change the way they practice. It’s the way we can motivate our patients to do the things that we think are good for them, when we can prove it. And it’s the way that we get insurance reimbursement for these kinds of services, which right now are poorly reimbursed, if at all. I think that’s what we need to do.

    Cross: Thank you. This is fantastic work. It’s very important work and it certainly will impact how practitioners and patients function in the future. I want to thank Dr Ilana Katz Sand for joining us today and enlightening us on her studies on diet and her future plans and studies on lifestyle and wish her the best of luck in the future. And congratulations on your brand new paper in Multiple Sclerosis Journal. This is Dr Anne Cross for InDiscussion.

    Katz Sand: Thank you.


    Multiple Sclerosis

    Randomized-Controlled Trial of a Modified Mediterranean Dietary Program for Multiple Sclerosis: A Pilot Study

    Mediterranean Diet Is Linked to Less Objective Disability in Multiple Sclerosis

    Dietary Factors and MRI Metrics in Early Multiple Sclerosis

    Multiple Sclerosis Functional Composite (MSFC)

    Kurtzke Expanded Disability Status Scale

    How to Incorporate Diet Into Multiple Sclerosis Care

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