COMMENTARY

Can Diet Alter Brain Function in MS?

Stephen Krieger, MD; Ilana Katz Sand, MD

Disclosures

November 05, 2018

Stephen Krieger, MD: Hi. I'm Dr Stephen Krieger and I'm here with Dr Ilana Katz Sand. We're both from Mount Sinai in New York, but we're here at the ECTRIMS [European Committee for Treatment and Research in Multiple Sclerosis] conference in Berlin, Germany, talking about multiple sclerosis (MS). In particular, you've done a lot of work in diet and MS, looking at how we can influence MS through behavioral and lifestyle changes. What have you seen at ECTRIMS on that topic?

Ilana Katz Sand, MD: I think it's a really exciting topic. It's one that patients are really interested in and where we have so much work to do. We're starting to see that work being done, so it's really exciting. I'll tell you a little bit about some of the observational studies that we've seen reported here and then about some interventions, including ours with diet.

In terms of observational studies, there was a nice poster by the Hopkins group (Kate Fitzgerald, Ellen Mowry) looking at the application of something called the Healthy Eating Index, which is an index that looks at diet quality.[1] They administered a food frequency questionnaire to about 280 patients with MS. With that food frequency questionnaire, they're able to look at many different dietary elements and they can classify people based on this Healthy Eating Index in terms of their diet quality.

They found that diet quality is associated with disability level in MS, which was really interesting. In addition, they found that people who were in the highest quintile of diet quality had faster processing speed, slightly faster walking speed, and slightly better manual dexterity.

Krieger: So, a couple of different neurofunctional outcomes driven by diet quality.

Katz Sand: Exactly.

Krieger: Were they able to tease out any cause-and-effect relationships or is this a set-up for an interventional project?

Katz Sand: That's exactly what it is. Really, it's a set-up for at least a longitudinal project. Many studies, including ours, are looking at cross-sectional data because that's what we have available and that's really the way to start. After that, you move into something that's longitudinal and then you really can move into interventions.

Krieger: But that's, of course, what every MS patient asks us: What kind of diet should I be on? And trying to answer that requires some of these steps.

Katz Sand: These things just have to be done. I'll tell you a little bit about our poster, where we used our colleague Dr Sumowski's cohort.[2] We looked at the baseline data in our group of patients with early MS who volunteered to be in the study; we had really nice, detailed neuroimaging and clinical data captured. They also completed a food frequency questionnaire.

Krieger: This is people with MS for less than 5 years? So, as we said, early MS?

Katz Sand: Yes. Early MS, young patients. In particular, we were interested in fatty acid intake because that's something that has been reported in the basic science literature. There are some small pieces of work that are epidemiologic in nature, associative, looking at fish intake and things like that. We were very interested in fatty acid intake.

We looked at the intake of monounsaturated fats, polyunsaturated fats, and saturated fat. We were surprised because we didn't find an association in terms of polyunsaturated fats or saturated fats. We did find an association between the intake of monounsaturated fats and measures of brain matter atrophy.

Namely, the primary measure we were looking at was cortical thickness. We chose to focus our study. All of the studies that we're looking at in diet are really focusing in on these measures because we think that some of these things may be neuroprotective. Brain matter atrophy, as you know, is the measure most closely associated with disability.

Krieger: And in particular, like you said, with things like cognition and fatigue. Measures of brain function.

Katz Sand: Exactly. So we found a really interesting relationship. We divided our group into tertiles of intake, and we found a clear relationship in terms of intake of monounsaturated fats and cortical thickness. I think the most interesting point is that we know that there's a relationship between T2 lesion volume and cortical thickness, so the more T2 lesions you have, the worse your cortical thickness is going to be. What was really interesting is that among the patients who had a high intake of monounsaturated fats, that relationship actually is really attenuated and becomes almost flat. From a theoretical standpoint, perhaps this really is a neuroprotective phenomenon that we're observing.

Krieger: That's a great point. A modulator of the effect of disease on cortical integrity.

Katz Sand: Exactly. A lot of times we think about the neurodegenerative process in MS and we think about parallels to aging. We wonder if some of these observations are just things that you would notice in healthy people. That particular observation shows that there is actually a disease-specific relationship here, which we thought was really interesting.

Krieger: That is quite right. Anything else that you're working on in diet that we should include here? Forward-looking things?

Katz Sand: I'll tell you a little bit about two interventions that I think are pretty interesting. One is ours. But first I'll tell you about another great poster that I saw, which was by Dr Brenton and Dr Goldman at University of Virginia.[3] They looked at a modified ketogenic diet, which is a hard thing for anyone to do. I think it's great that they did it because ketogenic diets have, at least in basic science literature, all kinds of potential benefits in terms of inflammation and neuroprotection.

They wanted to do a feasibility study because, as we're saying, it's a hard thing to do, and who knows if you'll be able to get people to commit to doing it or to actually do it. They recruited 20 patients who then followed the ketogenic diet for 6 months. They saw improvements in fatigue and depression, as well as improvement in measures of insulin sensitivity and a decrease in leptin levels. Really interesting and, I think, really nicely laying groundwork for future studies in that area.

Krieger: Sure. And a good rationale to pursue it, again, with it being a difficult diet. Again, this sort of aligns with some of the other data around these sorts of dietary effects.

Katz Sand: Exactly. I'll tell you a little bit about our poster on our pilot study, which was a randomized trial but a small trial of a modified Mediterranean diet in women with MS.[4] The main goals of our study really were about the clinical trial feasibility, because this work just hasn't really been done.

One of the things we want to know is whether it is going to be possible to recruit patients. Everyone says they're interested, but when it's actually time to sit down, sign up, and commit to making a major lifestyle change, but also to being randomized and having the possibility of either being in this group and having to make this major change or to being told that you're not in the group and you're kind of going to hang out here for 6 months—I think it's a difficult thing.

We were really excited that we had so much interest and we were able to recruit this in a single center in a fairly short period of time. Our target was 30 (15 and 15), but within our timeframe of about 9 or 10 months that we had to recruit, we were able to randomize 36. So we have 18 and 18, which was great.

The second thing we wanted to look at was whether everyone would finish the study, which was a concern in both groups. It's a concern in the intervention group because the diet, which I'll tell you about in a moment, is difficult. The concern in the non-intervention group is how to keep them engaged and how to get them to follow up. We were very pleased that 18 out of 18 people in the intervention group completed all 6 months of the study.

Krieger: That is remarkable.

Katz Sand: And 16 out of 18 in the non-intervention group. Unfortunately, one patient unexpectedly moved to England and the other was just impossible to get in for follow-up. But we were happy to not see a huge dropout rate.

[We call the diet] a modified Mediterranean diet, but it's more restrictive. I think people have all kinds of definitions of this, but we followed Mediterranean diet principles, including encouragement of fish, nuts, avocados—foods that are high in mono- and polyunsaturated fatty acids—fruits, and vegetables; and if you're going to have grains, they had to be whole grains. We completely eliminated meat, dairy, and most processed foods. It's a big change for most people.

Krieger: Especially for American eaters.

Katz Sand: Yes. Again, we were very pleased that people were so excited about it, willing to do it, and that they completed the study. We have a lot of different adherence measures that we're going to be looking at. We just finished the study last month, so it'll take us a little while to go through everything and do all of the analyses. Based on our participants' self-reported adherence—we had them come in every month for check-in and to fill out some questionnaires and things—the average adherence at the 6-month time point was about 90%, which was great.

We tried to really encourage people to be as honest as possible. [We told them that] this is a pilot study, we really want to learn about feasibility, it's completely anonymous, don't try to please us, we really want to know. We had them fill out [questionnaires] about what parts were hard, what parts were easier than expected. There were a lot of challenges.

We really learned a lot from running the study. The most interesting part is that although the primary aims were really about clinical trial feasibility, we also wanted to look in an exploratory fashion—figuring that we're going to be underpowered for almost everything—at some patient-reported outcomes. We had a statistically significant reduction in fatigue over the 6-month period. In 6 months, we were able to show that people had a reduction in fatigue. That was without us [requiring the presence of] fatigue as an entry point into the study.

Krieger: It's so prevalent and so top-of-mind that it's a very useful outcome measure.

Katz Sand: Exactly. In addition, we had improvement in the MSIS-29 (Multiple Sclerosis Impact Scale). People felt better. Many of the patients were so grateful to be included and really felt like their lives were better and they were healthier. [We do not know] whether these improvements are due to the fact that they lost a few pounds. The diet was designed to be weight-neutral, so we did not advise them on weight loss and we did not have them count calories. Obviously, when you change from eating things in one group to the other, people lost a little bit of weight.

On average, people in the diet group lost about 6 pounds, so about a pound a month. We have to look at whether those improvements in fatigue and MSIS were related to the weight loss. It's going to be hard to separate that out, of course. I think that if people feel better, this is what we're all about—helping people lead their best lives. If they feel better, I think that's a worthwhile goal.

Krieger: I think so, too.

Katz Sand: Ultimately, we're interested in diet as a disease modifier. I would love to work on how to scale this up and to look at whether the signal we saw in terms of the monounsaturated fats is something that's going to pan out. I would like to look at this longitudinally in an intervention with this type of diet and see what happens in terms of atrophy and these things. For now, I think we're just really pleased with the way the study went.

Krieger: It's a great first step. Credit to you for doing a randomized controlled diet study.

Katz Sand: Thank you.

Krieger: I think that's a great summary of what we're thinking about in diet as a marker of disease and as a possibility for intervention. Reporting to you on diet and MS from ECTRIMS in Berlin, Germany. Dr Katz Sand, thank you.

Katz Sand: Thank you.

Krieger: I'm Stephen Krieger, for Medscape.

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