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Podcast: Autoimmune Disease and The Paleo Diet: Case Studies

February 27, 2014
Podcast: Autoimmune Disease and The Paleo Diet: Case Studies image

Dr. Loren Cordain: I'm Loren Cordain, founder of the Paleo movement.

Shelley Schlender: I'm Shelley Schlender. This is the Paleo diet Podcast for August 2014.

Trevor Connor, you're a graduate student of Loren Cordain, and one of the projects you've tackled is to talk with many people who have had autoimmune conditions and then went on the Paleo diet. What led you to do this study?

Trevor Connor: It was relly Dr. Cordain's interest in exploring diet and autoimmune disease. He felt strongly that there's something there, and that if we can dig deep enough into it we can find a dietary trend that's affecting autoimmune disease. I'd certainly say so far from what we're seeing, that appears to be the case. But it's very exciting research, because compared to a lot of the other research, very new, very open. So that's one of the things that makes this a really exciting project to be involved in.

Shelley Schlender: How many people have you talked with who had an autoimmune condition and then went on the Paleo diet and either saw a difference or didn't?

Trevor Connor: That was one of the amazing things about this study, because initially we were just going to write a review paper. Then early in the process we said, "Let's try to get a case study or two." Dr. Cordain asked me to get on some of these autoimmune boards and ask people to participate.

Shelley Schlender: Just going to citizen boards on the internet and going to a forum and saying, "Who would like to tell me their story?"

Trevor Connor: Correct. Obviously, when you just have somebody telling you their story, there's a huge personal bias built in. So we said anybody that we have involved, we would like to get medical records from them.

Shelley Schlender: Before and after?

Trevor Connor: Right. So we can trace their whole medical history from before they were on the diet, to when they were on the diet. We did have one person who got off the diet, so obviously the medical records after. But for most of the people, they were still on the diet when they gave us the records.


Shelley Schlender: Now, it still is not exactly a controlled study, because you didn't know whether people who had not been doing this kind of diet would have had equally good results. You don't know whether people who did this kind of diet but didn't have good results didn't weigh in. So you had people who were enthusiastic about it calling you and saying, "I will participate and here are my medical records."

Trevor Connor: We're not trying to claim this is a perfectly controlled study at all. The approach we've been taking to this study is not this is a study to answer the questions. It was more, we're using this study to show there's a question worth asking. Then the hope, and what we're working on right now, is to bring in the funding so that we can do the proper controlled studies. Originally we were hoping for maybe two or three people. We had over 100 people volunteer for this study. We had criteria to at least have some control of the study for the subjects, and by the time we did eliminations for the criteria, we were down to 56 subjects with a variety of autoimmune illnesses. We really didn't have any idea what to expect, but there were some results that were really even surprising to us. One of the most promising was we had eight subjects with Crohn's disease.

Shelley Schlender: What is Crohn's disease?

Trevor Connor: Crohn's disease, and right now it's actually being debated whether it is a pure autoimmune illness, but it's essentially a condition of the gut where it appears that the immune system actually attacks and damages the lining of the gut.

Shelley Schlender: It can kill people too, Crohn's disease.

Trevor Connor: It is certainly not as deadly as many other autoimmune diseases, but it can have a dramatic effect on quality of life. I haven't personally read of any cases where it actually killed a person directly. But what you see is your ability to absorb nutrients decreases so much and has such an effect on quality of life that I think you start seeing other health issues drop up that end up, that can be what can kill the person.


Shelley Schlender: In your study you found eight people who had a dramatic change in their Crohn's disease on a Paleo diet?

Trevor Connor: We had eight volunteers who had Crohn's and went on a Paleo diet, and all eight went into remission on the diet, which was quite surprising to us. Eight went into remission.

Shelley Schlender: That's means it was gone.

Trevor Connor: Well, it's remission. Crohn's is a condition that is intermittent, so it will at times reappear. So when I looked through the ... Well, at times it will go into remission and the person will be able to function fairly normally, and then it will return. But what we were seeing in the medical records with these subjects is this very steady decrease in the symptoms, and when they went into remission you didn't see the normal return of the condition. There was one subject who was quite dramatic. He was diagnosed. He was put on medication. He didn't like it. He decided to try the diet instead. He went off medication. I have this great note from his doctor saying, "The patient has gone off of medication despite my strong reservations, and I don't think the diet is going to manage it in the long term." Then two years later I have another note from the same doctor saying, "Subject has been in remission for two years. Appears to correlate strongly with dietary changes."

Shelley Schlender: The doctor said this.

Trevor Connor: The doctor. This is the doctor's notes.

Shelley Schlender: You're grinning. Both of you are smiling about this. Loren Cordain.

Dr. Loren Cordain: Well, I think that many physicians just look upon this as a fad diet with no real rhyme or reason. Many physicians simply don't have the time to read the logic or the science to realize that this is a fairly well thought out idea, and it's not, well, we're just serendipitously pulling this food and that food group. As Trevor can tell you, we both have read thousands of papers that pointed us in this direction.


So we've taken it to a level that's much deeper than just superficially removing two or three food groups. We actually have explored it mechanistically. That's the beauty of working with Trevor is that he is a real logistician on putting together complex pieces of the puzzle that I myself have not been able to see.

Shelley Schlender: So Trevor Connor, you found that Crohn's disease was one where there seemed to be some success for people who stuck with the Paleo diet. Are there some other conditions that stood out for you as being pretty near how much they responded to a Paleo diet?

Trevor Connor: We ended up sticking with eight conditions, and we saw in most of the conditions a strong trend towards they were improving with the diet.

Shelley Schlender: What were some of those eight conditions?

Trevor Connor: Some of the big ones were type 1 diabetes, Hashimoto's thyroiditis, mixed connective tissue disorder, rheumatoid arthritis, multiple sclerosis. Like I said, always whenever I go through a list, by the time I'm halfway down I forget what I've already said, so I'm trying to think of the ones I've left out. But those were the main ones that we're really focusing on in the study. What was actually very promising to me, because we didn't have the level of control you would like to have, I guess for lack of a better word, the lack of randomness that we saw in the results, meaning there were some conditions like Crohn's where we saw dramatic results. There were other conditions, like mixed connective tissue disorder, where we saw really no improvement with the diet.

Shelley Schlender: I'm afraid I don't know what mixed connective disorder condition is.


Trevor Connor: As I was researching autoimmune diseases, I discovered that within the community they're divided into two classes, and certainly it's a continuum. But there's really what's called organ-specific autoimmune diseases, where one particular tissue gets attacked, so for example, thyroid disease where the thyroid gets attacked, is an organ-specific disease. So is diabetes. On the other end of the spectrum is what's called systemic autoimmune diseases. That's where multiple tissues get attacked. When people think of the archetypical systemic autoimmune disease you think of lupus, and that's why it can manifest many different ways, and there's so many complications related, because so many tissues get attacked. Mixed connective tissue disorder is a systemic autoimmune disease, and it's often related to lupus. That was a case where we really didn't see much improvement. I've actually been spending time, still working on looking at what's the difference. Is a systemic autoimmune disease different from an organ-specific. Is there commonalities in systemic and commonalities in organ specific. Some of the things that are coming out is it does appear that the mixed connective tissue disorders appear to be ... I mean, all of them have a genetic components, but there actually appears to be a genetic defect. If that's the case, if there's a genetic defect causing this, you would expect diet really can't do much about this. The organ-specific diseases, and this gets very complicated, so I hope I'm not doing an injustice with the simplification, they tend to be much more mediated by what's called a TH17 imbalance.

Shelley Schlender: Now TH17, can you say what that means?

Trevor Connor: It stands for T helper cell 17. We have in our immune system what are called T helper cells that really orchestrate the whole immune system. There's different types, and for a long time the two main T helper cells they were looking at were what's called TH1 and TH2, and it was really believed that autoimmune disease was a result of an imbalance towards TH1. Very recently, I think it was 2006 or 2008, they discovered TH17. As they've been studying it further, they're discovering more and more that all these autoimmune diseases are actually mediated by TH17.


There's also evidence coming out now, and again I'm simplifying a lot, but that the role that TH17 is designed for is actually really to help control and keep in balance the microflora of our gut.

Shelley Schlender: Trevor Connor, you say that something with the immune system ties back to how healthy the gut is, and not only how healthy the gut is, but how healthy and balanced are the 100 trillion little tiny microbes that are within our gut.

Trevor Connor: Absolutely, and actually so for the controlled study that we hope to do, one of the things that we're actually going to study is changes in the gut microflora when we put these people on a Paleo diet, because we think that's a big piece of the equation. To give a kind of a teaser, and this is part of what I'm writing about in the paper, but just with a big qualifier, this is really complex, and any immunologist who hears this is going to go, "Wow, you over-simplified that." But the problem is, to explain this in its full detail, we would be here for an hour, and anybody who's not an immunologist would be bored to death. As long as you're okay with me giving a bit of a simplification, here's a really interesting piece to the puzzle of how this relates. There are studies out now, or at least reviews out, hypothesizing that one of the potential roles, like I said, of TH17 is to help control the microflora. The idea is somehow the microflora gets through, or somehow the content of the gut gets through. It causes this inflammation and TH17 is this highly inflammatory, very powerful helper cell that comes it, but it's dealing with a bit of an extreme situation and tries to get it back under control.


Shelley Schlender: If the gut leaks, that word that scientists used to say was ridiculous, but now that kind of terminology is even appearing in science. Leaky gut is being acknowledged, and that there's ways to measure, that there are metabolites coming through that show that there was undigested proteins or weird fragments that came into the circulatory system that just freaked out the immune system.

Trevor Connor: Well, let's take it one step further. Here's something that a lot of the people listening to this might not have heard of, and again, a bit of a simplification. But we have macrophages that line our gut.

Shelley Schlender: Those are Spongebob Squarepants, that they kind of go and soak up things that they think are too much there.

Trevor Connor: Pretty much. There's a particular type, which is called a CD14 negative microphage, that sits right on the inside of your digestive tract. Basically, it's job, because you are always getting a bit of a load from your gut, you're always having a little bit of inflammation right at that surface level, their job is actually to down-regulate the immune system, to prevent the immune system from overreacting to what's happening right at the border of your gut. That's a role of the CD14 negative macrophages. When they become CD14 positive, they do the exact opposite. Instead of down-regulating the immune system, they activate it. One of the things they do is push a balance towards the TH17 cells. One of the things that's very fascinating with this, as I was researching this I found five or six studies now showing that wheat consumption, for some reason, causes a conversion of CD14 negative macrophages towards CD14 positive.

Shelley Schlender: Let's see. CD negative is the good guy.

Trevor Connor: They're both good guys, but the idea is the CD14 positive is, they've become CD14 positive when they say, okay, we've got this load from the gut. We need to respond to it. Let's push our T helper cells towards this TH17 balance, and have them come in and solve this issue.


Shelley Schlender: I guess another way to put it is that there is a growing realization or talk about how many people on a modern diet tend to have more inflammation in their bodies. Their bodies are just always a little bit chronically inflamed, and that leads to a lot of problems for our heart and our digestion and or joints, all kinds of places. You're saying that wheat takes this T helper that can be good or bad, well it can either be inflaming or cooling things off, and it tells it to heat things up.

Trevor Connor: I'm trying not to get too much into the complexity, but that's kind of it. When I was talking about what's important in autoimmune disease, and they used to look at the TH1-TH2 balance, probably what's more important is looking at the TH17, what's called T regulatory cell balance.

Shelley Schlender: So there's a new thing to look at, because we all are so wanting to have something we could measure, to tell. For instance, how do you measure whether somebody actually is eating a Paleo diet. Because people can say they are and then go off to their favorite bagel place or Great Harvest bread place and eat a wonderful, tasty whole wheat muffin now and then, and say they're still doing Paleo.

Trevor Connor: Well, that's one of the issues, and that's why for this study, because we don't have the control of their diet, we weren't actually studying the Paleo diet. There's just too many factors there. What we really focused on was people who went on a wheat-free diet. We were looking at really the effects of wheat on the immune system and potentially in autoimmune disease. That's a place where it's easier for people to report, "Yes, I have been eating wheat," or "No, I haven't been eating wheat," as opposed to "Yes, I've been on a Paleo diet."

Shelley Schlender: And it sounds like, Trevor Connor, that in a more formal study you could actually take blood samples from someone to see whether or not they have indications of undigested proteins of wheat somewhere in their circulatory system, so that even if they say they never touch it, you can say, "Well, actually you do."


Trevor Connor: Exactly. You can do that. But our hope with a controlled study is that we will actually provide them with their food. So we'll go, "Here's your Paleo diet. We've made it for you. Eat this." And we'll give them the guidelines.

Shelley Schlender: What if they sneak off and still go and have something that's non-Paleo.

Trevor Connor: Well, that is the unfortunate nature of the beast whenever you're doing a nutrition study. You try to control diet, and you can always generally expect a little bit of breaking of the diet. Whether they are honest with you about that or not I think is actually the bigger issue.

Shelley Schlender: But you're planning this study where you would measure things like TH17.

Trevor Connor: The hope is we would measure their T cell balance. We would measure changes in their microflora. We would also look for markers of inflammation. So really look at all components of this potential equation, and see what sort of changes we see with the diet.

Shelley Schlender: Do you have some ideas for people to fund this or to do the test analysis for you?

Trevor Connor: We certainly have put together the resources we need to do this study. So really the issue is bringing in the money, and that has been, especially in this ... Right now when there isn't a ton of funding out there, it has been a huge challenge.

Shelley Schlender: How much money would it take?

Trevor Connor: Well, this is where, and Dr. Cordain could talk much more about this than I can, but this is where I'm certainly learning as a student. Initially they asked me to design the study. I designed the ideal study. They looked at it and went, "This is $2 million dollars. That's not going to happen. So now let's figure out what we can actually do." What I am learning is, you take more of an approach of, we're probably going to do multiple studies. The initial study is not going to be anywhere close to the ultimate study we want to do, but will be much cheaper, and hopefully we can get enough results out of that that then we can go to bodies like the NIH and say, "Now we have some evidence. We have some numbers for you. Can we get the funding for a bigger study?" That's the process that we're hoping to go down.


Shelley Schlender: In the last few years there have been some studies funded initially by Kickstarter campaigns, where they have been able to get for a research study, $100,000, $200,000 through Kickstarter.

Trevor Connor: We are doing similar things. There are other bodies out there that they give these fundings for what they would call less traditional, or riskier initial studies to look at, basically much more modest studies, like what we would hope to do initially, to see if there's something to this, and then use that to go for larger funding. So we've been pursuing those.

Shelley Schlender: I guess what we're all looking for is something where we could go, "I think I have these aches and pains. Am I somebody who's susceptible because of something I could measure? If I change something, will that measurement change?" To just help you know whether or not to try it or not.

Trevor Connor: Oh boy, that is the big question. If we come out of all of this with something that's relatively easy to measure, that's not cost prohibitive, that could help people and allow us to tell them what potentially to do with their diet, that would be amazing. I think that's the hope of a lot of people in nutrition research. But I think that's a very, very ambitious goal that we're probably not going to see in the next few years.

Dr. Loren Cordain: That's all for this edition of the Paleo Diet Podcast. Visit my website,, past episodes, and for hot links, the experts and studies that we talked about today.

Shelley Schlender: Our theme music is by Chapman Stick Soloist, Bob Culbertson.

Dr. Loren Cordain: If you want to send me questions or comments, the place to go is

Shelley Schlender: For the Paleo Diet Podcast, I'm Shelley Schlender.

Dr. Loren Cordain: And I'm Loren Cordain.


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