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RHR: New Treatment for SIBO and IBS-C—with Dr. Kenneth Brown

revolution health radio

In this episode we cover:

  • 04:26 The problems with current treatments
  • 08:03 The underlying issues with IBS-C
  • 11:12 The connection between SIBO and rosacea
  • 12:25 The drawbacks to Xifaxan/rifaximin
  • 15:48 How Atrantil works
  • 21:08 Studies published on Atrantil
  • 25:36 Clinical pearls for treating with Atrantil
[smart_track_player url=”http://traffic.libsyn.com/thehealthyskeptic/RHR_-_New_Treatment_for_SIBO_and_IBS-Cwith_Dr._Kenneth_Brown.mp3″ title=”RHR: New Treatment for SIBO and IBS-C with Dr. Kenneth Brown” artist=”Chris Kresser” social=”true” social_twitter=”true” social_facebook=”true” social_gplus=”true” ]

Chris Kresser: Hey, everybody, it’s Chris Kresser. Welcome to another episode of Revolution Health Radio. This week, I’m going to be talking with Dr. Kenneth Brown. He received his medical degree from the University of Nebraska Medical School and completed his fellowship in gastroenterology in San Antonio, Texas. He’s a board-certified gastroenterologist and has been in practice for the past 15 years with the clinical focus on inflammatory bowel disease and irritable bowel syndrome, or IBS. For the past 10 years, he’s been doing clinical research for various pharmacologic companies. It was during these years that he saw the unmet need for something natural that could help his IBS patients. He had been working on a development of Atrantil for the past six years and officially launched Atrantil one year ago. He developed this product with the intent of helping those suffering from the symptoms of IBS, which we now know are caused by bacterial overgrowth.

So, I reached out to Dr. Brown because we started to use Atrantil in our practice, at California Center for Functional Medicine, and had some good results with it, and there definitely is a lack of treatments that are effective and safe to use over the long term for SIBO in general, but particularly for methane-predominant SIBO and also for constipation-predominant IBS. And when I learned about Atrantil and Dr. Brown’s work here and the research he has done on it so far, I wanted have him on the show to talk about it further. So without further ado, let’s dive in.

Chris Kresser: Dr. Brown, thanks so much for joining us. It’s a pleasure to have you here.

Dr. Kenneth Brown: Oh, Chris, thank you so much for having me on your show.

Chris Kresser: So I thought we could just start up with a little bit about your background and what led you into research on SIBO and IBS, particularly constipation-predominant IBS.

Dr. Brown: Yeah, so I’m actually a practicing gastroenterologist in the Dallas, Texas, area, and I’ve been doing clinical research for the last 10 years as well. This all kind of started when we were doing research for Salix at the time, on Xifaxan, and I think you’ve had, Dr. Pimentel was a guest on your show, and that’s when he and I came in contact and we were trying to help fill their study, and that’s when he noted that SIBO would be a really big problem, and it’s a very exciting time to be involved with it. He demonstrated with rat models at that time the difficulty it would be to get rid of bloating and constipation in all those people that actually have nothing, and the way that they were going really was not going to work with just the Xifaxan. So it was literally 10 years ago where I was like, “Wow!” So if we could figure out the methane aspect of this, we would really be onto something really cool and that’s initially where all the ideas kind of started.

The problems with current treatments

Chris Kresser: Great. So, I’m going to step back just for my listeners who aren’t as familiar with all the terms we’re throwing around here, but many of you have been listening to the show for a while and know about SIBO, small intestinal bacterial overgrowth. You know that the small intestine normally shouldn’t have much bacteria, but occasionally it will become overgrown with bacteria, and that bacteria can produce hydrogen or some of the species of organisms which can produce methane. So, when you have SIBO, you can have a SIBO that’s hydrogen predominant, meaning you have mostly bacteria that are producing hydrogen, or you can have SIBO that is methane predominant, where you have mostly organisms that are producing methane gas, or you can have both, and they tend to present with different symptoms and they require different treatments. And so, part of the challenge here has been that the most effective treatment has been rifaximin [brand name Xifaxan], which is a drug that’s used to treat primarily hydrogen-predominant SIBO, and I think, if I remember off the top of my head, the efficacy of rifaximin for treating methane-predominant SIBO is only about 40 to 45 percent used, when it’s used alone. Does that match with your recollection, Dr. Brown?

Dr. Brown: Well, I think it’s a little bit less than that, actually. In their target studies that they just got published, they are 41 percent for the diarrhea predominant, which is how they got their FDA approval, and so we know that it’s a little bit less or significantly less when used alone for methane.

Chris Kresser: Wow. Yeah, that’s not very effective at all.

Dr. Brown: Yeah, so that’s actually why I’m treating all these people and they’re so frustrated.  As a gastroenterologist, I’m frustrated. As a patient, they’re frustrated, and that’s why we really started doing some of the research on this.

A promising treatment for SIBO and IBS-C

Chris Kresser: So, let’s talk a little bit about some of the other treatments for IBS-C and why they are lacking and why they haven’t been effective, because people are typically—a conventional gastroenterologist isn’t even necessarily prescribing rifaximin, they’re using other medications as a first line for this, right?

Dr. Brown: Correct. So, I see a lot of people that tend to fail other things, and one of the biggest issues is that almost everything out there is some form of laxative. Everybody’s focusing on colon, and you’re way ahead of the curve that already realizing that there’s a lot going on in the small bowel but needs to be addressed. But a lot of times, people say, “Oh, you’re bloated and constipated. Here, take this …” And so there’s lubiprostone, which is Amitiza. We’ve got Linzess out there. There’s a new one called Plecanatide, which is coming out. These all can help people go to the restroom, but they still feel very bloated and distended and have an “uncomfortableness,” so they get very frustrated with that.

Chris Kresser: And they’re not really addressing the underlying cause of the problem, which is perhaps the biggest issue.

Dr. Brown:  Correct. That’s the biggest thing. It’s that it’s just putting a Band-Aid on it and that’s why they get so frustrated and really start looking for alternative treatments.

Chris Kresser: I think there are even drugs for IBS-C in the past that had to be pulled because of severe side effect. I’m thinking, was Zelnorm one of those or—

Dr. Brown: Zelnorm was, and it was a good drug. We liked it. When it worked, it worked really well. And in fact, not to get off topic, that was when Pimentel first looked at Xifaxan. He was treating people with Xifaxan during the day and Zelnorm at night. That was his regimen because it worked as a phase III contractant. So yes, drugs have been pulled off because of that. When Zelnorm was there, it worked only 10 percent better than placebo, but when it did, it worked well.

Chris Kresser: Hmm-mm.

Dr. Brown: And that’s also one of the drawbacks that these products that are out there are really only slightly better than placebo and some of them can cause a ton of money.

The underlying issues of IBS-C

Chris Kresser: Right, right. Okay. So, we have a situation where the currently available treatments have been inadequate because they’re not addressing the cause or when they’re attempting to address the cause with rifaximin, they’re just not very effective at doing that when the cause is methane and the symptom is constipation rather than hydrogen and diarrhea, as is the case with IBS-D. So, let’s step back a little bit more and talk about the underlying causes of IBS-C. So if someone has IBS, they have constipation, the conventional paradigm, they’re labeled with this diagnosis, which basically just describes their symptoms, but there’s rarely any investigation into what’s actually happening under the hood, so to speak.

So you mentioned SIBO, but what about disruptive gut microbiome in general? Have you found that that’s an issue for these patients?

Dr. Brown: I think there’s so much overlap with this and what happens is, is that if somebody comes in and they go see a doctor and they end up maybe seeing even a specialist, like a gastroenterologist like myself, they get an endoscopy, colonoscopy, blood work. It’s normal and unfortunately, a lot of people get sort of patted on the head and said, “Oh well, you have IBS,” and the problem is, is that’s kind of a trashcan diagnosis. Really, anybody that has abdominal pain, if they got a change in bowel habits, then you qualify as having IBS. And once you get labeled, I think a lot of times doctors stop thinking about what else could be going on, and that’s where some of the functional approaches come in. What I tell my patients is that I do see a lot of people that actually improve when we do treat them with Atrantil, and what I tell them is, is that it’s possible that either you had an infection, took antibiotics, even went through a stressful situation and something shocks your small intestine. When that happens, bacteria can start to grow in that area. Then, every time you eat, specifically, starchy foods, then the bacteria will break down the food before you can and then that results in all the bloating and discomfort.

Now, the interesting thing is, I’m starting to see this very close link to where you’re going right here, which is the disruption of the microbiome. We now know that even a lot of research is showing that we’re having an overall inflammatory process that happens in the body. You can call it “leaky gut” if you want, you can call it “intestinal permeability.” Whatever you want to label it, we do know that people feel miserable beyond their intestines and that’s where—once you address that, and I said, “Look, it’s not in your head. We don’t just pat you on the head and say this. I really think that this could be going on and this could be leading to these symptoms, not only in your intestines but throughout your whole body.

Chris Kresser: Yeah. And that’s why there’s such high comorbidity with IBS and depression, anxiety, all kinds of other health conditions. It’s not because it’s just in their head, it’s that low-grade inflammation that’s happening in the gut that’s affecting it as you would expect it to every part of the body.

The connection between SIBO and rosacea

Dr. Brown: Exactly. I mean, we’re seeing people—and you’ve probably had the same results in the practice of functional medicine, people that have skin issues, once you treat them, certainly if you treat them from their intestines, their skin gets better. People that have restless leg, pelvic floor syndrome, all these other what we’re calling “trashcan diagnoses,” I’m seeing a lot of my patient gets better after we treat them.

Chris Kresser: Yeah. It’s really fascinating. I don’t know if you saw this, a recent follow-up from an original study that was done showing 100 percent correlation between acne rosacea and SIBO patients, and then they follow them for several years and found that 100 percent of people who successfully eliminated SIBO had a significant improvement in their rosacea. So, it wasn’t just an association, they actually were able to prove causality there, which is pretty amazing.

Dr. Brown: Yeah. I’ve had patients who have been to multiple dermatologists, and I had one patient that was so sweet. She drove in from Austin, which is four hours away just to let me know that she’d suffered from rosacea for about eight years, and after treating her SIBO with Atrantil, that went away and she drove in to tell me so that I could let other dermatologists know. I thought that was fascinating.

The drawbacks to Xifaxan/rifaximin

Chris Kresser: Yeah. So let’s talk a little bit more about rifaximin, which is the drug of choice for SIBO typically at this point, and one of the issues that we’ve already covered is that it’s not very effective for methane-predominant SIBO. But there are some issues too, like costs and insurance coverage and recurrence. Can you talk about those a little bit?

Dr. Brown: Sure. So, let’s look at the target studies. We just got Xifaxan approved by the FDA to treat IBS-D. In those studies, really, it was 41 percent effectiveness versus overall versus 31 percent. So we get a 10 percent than placebo. In defense of that in my practice, when I use it on the right person, my results are a little bit better in the IBS-D population. There is still almost 60 percent recurrence rate with these people, so they’re going to come back in and then you did mention that it is very expensive. If you don’t have insurance, it’s essentially cost prohibitive. If you do have insurance, it still can be extremely expensive with copays and such. So the problem is that … okay, let’s back up and talk a little bit, you had mentioned at the very, very beginning you’re telling your listeners about methane production. The issue and the problem that makes it hard to treat SIBO in the first thing is the location of it. It happens to be in the small bowel, but it happens to be intraluminal or inside the intestines, so a lot of the medications we’ve used in the past, metronidazole, sulfa drugs, things like that, those get absorbed so you have this system effect and little effect in the intestines. So Xifaxan, at least, is poorly absorbed, so it does seem to work in the right area, so the first problem is that. Now, the problem that Xifaxan runs into, is that the type of organism that’s actually producing the methane is called an archaebacteria. These are known as methanogens, and they’re actually really cool in the sense that they’re very old organisms. They’re in their own kingdom. They sort of constitute a domain in a kingdom of microorganisms where they don’t even have any cell nucleus or other membrane-bound things like other bacteria.

Chris Kresser: Right. They’re not bacteria, they’re not yeast (just to fill people in here) and they’re in their own place here taxonomically.

Dr. Brown: Yeah, so it’s interesting in that our modern-day antibiotics work in a way that does not affect archaebacteria. So let’s look at Xifaxan, for instance. Xifaxan actually works by binding to the bacterial RNA polymerase so that it doesn’t let the bacteria produce protein. So I think there was a paper that came out not too long ago where they talked about increased efficacy using guar gum plus Xifaxan.

Chris Kresser: Yeah, yes.

Dr. Brown: And that’s kind of interesting in the sense that the bacteria, the more active they were, the more they were absorbing both the guar gum and the Xifaxan because the Xifaxan had to be gobbled up.

Chris Kresser: Right. Dr. Pimentel put it, “You gotta feed ’em to kill ’em.”

Dr. Brown: Yeah. So that’s one of the things about archaebacteria is that it’s not going to do that. And so the exciting thing and one of the reasons why we developed this is that we don’t need the archaebacteria to be eating a whole lot because the way that the quebracho works and the conker tree is that it actually disrupts the methane production of it and it weakens the wall of the archaebacteria.

How Atrantil works

Chris Kresser: Cool. I mean, this is a good segue, let’s talk about Atrantil, and I’m glad that you pronounced it because now I know I was pronouncing it completely incorrectly in the intro.

Dr. Brown: Don’t worry. Even my patients that love it mispronounce it, I keep telling them, it’s like, “Ah, my belly feels better.”

Chris Kresser: Right. Okay. Great. So yeah, tell us a little more about how this fills the gap. You already mentioned two of the ingredients, but let’s start it with what’s in this and then what it does that other treatments are not doing right now.

Dr. Brown: So, what we developed is very specifically for this, and so the key to Atrantil is that the molecules work together and they stay intraluminal, meaning, they don’t really get absorbed or they’re very poorly absorbed. So the first ingredient is M. balsamea, which is actually peppermint leaf, so a very, very small amount of it. But we wanted to use the actual leaf instead of the oil because it has polyphenols in it, and the polyphenols are those molecules that are good for you that we find in the Mediterranean diet and such. That calms the area down and then it allows the other two ingredients to do their job. The second ingredient is something you probably never heard of and it’s called quebracho colorado, and what that is, is that it’s a very large flavonoid, which also is a polyphenol, and that comes through the intestine, and what it does is it actually soaks up the hydrogen and absorbs gas, and what’s that going to do is that’s going to starve the archaebacteria. And then it happens to be from the bark of a very old tree that actually has natural defense against fungus and archaeal species, which is why we chose that particular molecule, and so what it does is, as it comes with contact with archaeal species, it weakens the wall. Then the third ingredient, the conker tree, which is known as a saponin, does two things. It actually kills—it’s bactericidal, meaning it kills bacteria—but it very specifically can shut off the enzymatic production of methane from the archaeal species. So to sum it up, we got one ingredient that calms the area, the second one starves the achaebacteria, and the third one shuts off the methane production.

Chris Kresser: Makes sense given the pathology of SIBO and IBS, and you’ve done, I think, two papers on this. There it is, Atrantil. If only we have video, people could see that. You published a couple of research on this, with the second one very recently published—which I read, thanks for sending that. One thing, before we dive into the specifics of that, it stuck out in the second paper was that some researchers have suggested that people