Are you dealing with SIBO? If so, you’ve probably tried a low-FODMAP diet and noticed significant improvements in your symptoms. Once you’ve noticed such an improvement, it’s easy to think that this must be the answer—a low-FODMAP (or low-carb) diet has cured you! Unfortunately, this is not the case. A low-FODMAP (or low-carbohydrate) diet will keep symptoms under control simply by starving the bacteria in your small intestine. When these bacteria don’t have food to eat, they aren’t able to metabolize that food and produce gas as a result. This gas is what causes the common symptoms of SIBO—bloating, abdominal pain, diarrhea (in the case of hydrogen gas), and constipation (in the case of methane gas) (1).   But starving the bacteria over the short term does not eradicate the bacteria, which is what we’re trying to accomplish, as the small intestine is not supposed to contain much bacteria. If you continue this restriction for a long period of time in an effort to kill the bacteria, you’re also starving the bacteria in your large intestine that should be there and that play a vital role in your health. Simply put, a low-FODMAP or low-carb diet does not eradicate an overgrowth in the small intestine in a short period of time, and continuing on a long-term low-FODMAP/carbohydrate diet in an effort to starve the bacteria to death has potential detrimental effects on the bacteria in the large intestine. I have had clients who have been on long-term low-FODMAP diets prior to working with me who still have positive breath tests for SIBO despite their restricted diet. There is a difference between controlling symptoms and actually clearing the bacteria. We want to do the latter, which has the added benefit of improving symptoms as well.

The Negative Impact of a Long-Term Low-FODMAP Diet

There have been limited studies on the long-term impact of low-FODMAP diets on microbial balance in the large intestine. The studies we have showing the impact of short-term FODMAP restriction on the microbiome, however, do not bode well for the long-term implications. FODMAPs are fermentable carbohydrates that help to feed the beneficial bacteria in the large intestine. When you begin to think about them this way, it becomes a lot easier to understand why adhering to a diet low in the substrates that our healthy gut bacteria thrive on may not be a great idea.

Is your SIBO diet controlling your symptoms or actually clearing the bacteria? #sibo

Indeed, the studies to date on the effects of FODMAP restriction show exactly what we would imagine would happen when restricting these beneficial substrates: the overall amount of bacteria was decreased (by 47% in this study), along with a decline in bacteria that produce butyrate (a beneficial substance made when probiotics feed on fermentable fibers) (2). While this particular study did not show a decrease in the probiotic strain bifidobacteria, another study has (3). In my clinical experience, it is very common to see low levels of both the bifidobacteria and lactobacillus strains in my client’s stool tests if they’ve been on long-term low-FODMAP diets. While these bacteria would likely thrive once again with the addition of prebiotic substances, staying in a chronically diet-induced altered microbiological state is likely not a healthy choice when you start to think about the importance of our microbiome and its effect on our health. Clearly, more research needs to be done in this area if patients are going to be on long-term low-FODMAP diets. However, after reading this article, it is my hope that you won’t need to be on a long-term low-FODMAP diet to keep your symptoms under control.

Treating SIBO

So if you’re not treating your SIBO with diet, what is used to treat it? Rifaximin is the most commonly used antibiotic for treatment of SIBO and has been shown to be safe and well-tolerated (4). Figures vary on its efficacy (with rates as high as 87% in one study), but on average it is about 50% effective (5). However, this may not take into account the necessary difference in treatment for those with methane-positive SIBO. A study on those with methane-positive SIBO shows that when rifaximin is combined with another antibiotic, neomycin, it is about 85% effective (6). If you’re getting tested for SIBO, make sure you’re getting tested for both methane and hydrogen. These tests will guide your practitioner in treating you more effectively. Herbal antimicrobials have been shown to be at least as effective as rifaximin, and about 57% of those who fail on rifaximin will succeed on herbal antimicrobials (7). I have personally seen this the other way around as well; those who fail on herbal antimicrobials usually do well with rifaximin. Others may need to do multiple rounds of either herbal or pharmaceutical antibiotics to clear the overgrowth. Whether you choose herbal or pharmaceutical antibiotics, the important thing is that you are using something that will eradicate the bacteria instead of covering up the symptoms with diet change. You’re getting to the root cause of your symptoms!

Diet during SIBO treatment

Now that you’re being treated with herbal or pharmaceutical antibiotics, what should you eat? If you listened to Chris’ recent podcast with Dr. Pimentel, you’ll know that having happy and fed bacteria is a good thing when treating SIBO—this is not the time to be starving them, as they will “hide” and become more difficult to eradicate. Eating FODMAPs and carbohydrates is exactly what you want to be doing! In my own practice, I recommend that clients undergoing treatment eat as many FODMAP foods as they can tolerate and that they do not go on a low-carb diet. (I like to see a minimum of 100 grams of carbohydrates daily, and more, if tolerated.) I also will typically add some kind of prebiotic if the client can tolerate it. A study that compared rifaximin alone versus rifaximin treatment plus partially hydrolyzed guar gum supplementation showed that providing fermentable carbohydrate along with the antibiotic improved success rates from about 62% (rifaximin alone) to 87% (rifaximin plus guar gum) (8). Of course, I don’t want my clients to be miserable with digestive symptoms during this time, so treatment is always personalized to each client. Some may have no problems whatsoever eating FODMAPs or high-carbohydrate foods, while others may be very sensitive. I encourage clients to eat the maximum amount that they are comfortable with and remind them that in the end, feeding these bacteria is a good thing. They may experience some uncomfortable symptoms like bloating or gas during this time, but as long as it is not interrupting their life or causing pain, the more FODMAPs or carbohydrates they can eat, the better.

Diet After SIBO Treatment

As many SIBO sufferers know, SIBO has a high rate of recurrence, which begs the question: what should you be eating after treatment to prevent another overgrowth? In my eyes, that’s the million dollar question right now, and it’s a question we don’t have the answer to quite yet. For now, I have my clients eat whatever they can tolerate on a healthy, real-food, ancestral diet. If they need to restrict FODMAPs slightly or eat rapidly digested carbohydrates to keep symptoms under control, that’s okay. (However, if you can’t tolerate FODMAPs or complex carbohydrates after your treatment, you’ll definitely want to retest to make sure that you’ve completely eradicated the overgrowth in the first place.) We’ll also investigate any potential underlying causes of their SIBO, such as low stomach acid, pancreatic enzyme insufficiency, intestinal motility disorders, and so on. I know from speaking with Chris that he has come to believe that SIBO—and especially recurring SIBO—is often a symptom of a deeper problem. The solution in that case isn’t just to keep treating the SIBO, but to address that root cause. There’s a lot we still don’t know about SIBO. As we learn more, some of these protocols may change, but I hope this article has given you a better idea of what you should be doing to heal from SIBO with the knowledge we have now. Now I want to hear from you: What has been your experience with SIBO? This is a guest post written by Kelsey Marksteiner, RD. Kelsey is a Registered Dietitian with a Bachelors degree in Nutrition from NYU and a Master’s in Human Nutrition and Functional Medicine. She works in private practice and recommends individualized dietary therapy focusing on biologically appropriate diet principles to aid her clients in losing weight, gaining energy, and pursuing continued health. She is a firm believer that everyone is different, and she tailors her plan for each and every individual. Through her work, she aims to meld the dietary wisdom of traditional cultures with the latest science in integrative and functional medicine to create plans for her clients that work in the modern world. You can learn more about Kelsey on her staff bio page, or by visiting her private practice website. Join her newsletter here!

A central principle of functional medicine is addressing the underlying cause of a disease, as opposed to just treating symptoms. In a previous article on the blog, I discussed the connection between overall gut health and the thyroid. In this article, we’ll focus on the microbes themselves and the many ways in which they are connected to thyroid function.

The importance of microbes and their metabolites in endocrine health

In recent years, the microbiota has been implicated in numerous chronic diseases, from obesity to inflammatory bowel disease to multiple sclerosis (1). It really should be no surprise that it also has a profound impact on endocrine organs like the thyroid. Disruption of the intestinal flora and subsequent impaired thyroid function was first hypothesized back in the early 1900s, long before the terms “microbiota” and “microbiome” were even coined (2).   Today, microbial sequencing of human fecal samples allows us to measure compositional differences in the microbiota. A 2014 study found that individuals with hyperthyroidism had significantly lower numbers of Bifidobacteria and Lactobacilli and significant higher levels of Enterococcus species compared to healthy controls (3). No equivalent study has yet been done in individuals with hypothyroidism, but given that 90 percent of hypothyroid cases are autoimmune in nature (4) and the fact that an altered microbiota has been implicated in countless other autoimmune diseases, it’s quite likely that dysbiosis plays a significant role (5).

Will healing your gut improve your thyroid function?

Microbes recognize a number of different host endocrine molecules, including adrenaline, noradrenaline, sex hormones, and thyroid hormones, and can even change aspects of their metabolism and virulence in response to these signals (6). Moreover, germ-free rats, which are raised in sterile conditions and lack gut bacteria altogether, have smaller thyroid glands than conventionally raised rats, suggesting a crucial role for these microbes in thyroid health (7).

Gut bacteria influence nutrient availability

The epithelial cells that form the lining of the gut have fingerlike projections called villi, which increase the surface area for transporting nutrients into the body. When the gut is inflamed, as is often the case with microbial dysbiosis, these villi can become truncated, resulting in impaired nutrient absorption. This includes nutrients like iodine and selenium, which are vital for thyroid health. While the microbiota provides many benefits to the host, it also competes with the host for nutrients. The nutrients that are essential for our cells to function properly are also important nutrients for our microbes! The composition of the microbiota may therefore influence a person’s requirement for various nutrients. In fact, a 2009 study in mice suggested that the microbiota competes with the host for selenium when selenium is scarce, impairing synthesis of selenoproteins, which are necessary for proper thyroid function (8). In another study, rats fed kanamycin, a broad-spectrum antibiotic, had significantly lower iodine uptake by the thyroid (7).

Gut bacteria and LPS

Lipopolysaccharide, or LPS, is a component of bacterial cell walls. When intestinal permeability is increased, often as a result of gut dysbiosis, LPS can “leak” into the bloodstream. This can wreak havoc on the thyroid in a number of ways. Thyroid-stimulating hormone (TSH) induces the thyroid to produce T4. T4 is the inactive form of thyroid hormone and must first be converted to T3, the active form.  Our bodies produce an enzyme called iodothyronine deiodinase that is responsible for making this conversion. LPS has been shown to inhibit this enzyme, decreasing the amount of active T3 in circulation (9). Not only do you need active thyroid hormone, but you also need receptors for thyroid hormone on cells throughout the body. Even someone whose thyroid hormone panel looks perfect could suffer from symptoms of hypothyroidism if their body does not produce enough receptors to receive signals from the thyroid. LPS has been shown to decrease expression of thyroid receptors, specifically in the liver (10). LPS also induces expression of the sodium-iodine symporter (NIS) in thyroid cells, increasing iodine uptake in the thyroid (11). Since iodine is important for thyroid health, this might sound like a good thing, but excess iodine (especially with concurrent selenium deficiency) has been found to contribute to the development of Hashimoto’s, the autoimmune form of hypothyroidism (12).

Gut bacteria influence conversion of T4 to T3

Remember in the last section how we said that inactive T4 must be converted to active T3? Well, about 20 percent of this conversion takes place in the GI tract! Commensal gut microbes can convert inactive T4 into T3 sulfate, which can then be recovered as active T3 by an enzyme called intestinal sulfatase (13). Bile acids present another interesting connection between gut bacteria and thyroid function. Primary bile acids are produced in the gallbladder and secreted into the small intestine following the consumption of fats. Metabolism of primary bile acids by the gut bacteria results in the formation of secondary bile acids. These secondary bile acids increase activity of iodothyronine deiodinase (the main enzyme that converts T4 into T3) (14). We’ll see one more way that gut bacterial metabolites influence thyroid health later when we talk about prebiotics.

SIBO and the thyroid

Thyroid function is also closely related to small intestinal bacterial overgrowth (SIBO). In a healthy individual, the majority of microbes are concentrated in the large intestine. In SIBO, certain bacteria and archaea are able to colonize the small intestine and proliferate, causing bloating, gas, and distention, among other unpleasant symptoms.   The connection between SIBO and the thyroid is underappreciated. A 2007 study found that among people with a history of autoimmune hypothyroidism, 54 percent had a positive breath test for SIBO compared to 5 percent of controls (15). It is currently unknown whether the relationship is causal. Since thyroid hormones help stimulate gut motility, it is also possible that low motility and constipation provide an environment in the small intestine that is conducive to bacterial overgrowth. This may be one of many examples of bidirectional interaction between the host and its resident microbes.

Conclusion: heal your gut to improve thyroid function

So how can we apply this information? Here are four ways that you can improve your thyroid function:

1. Eat plenty of fermentable fiber Bacterial metabolites are potent endocrine modulators. When you consume fermentable fibers like cassava, sweet potato, or plantains (prebiotics), your gut bacteria ferment these fibers and produce short-chain fatty acids (SCFAs). SCFAs have been shown to inhibit enzymes closely involved in epigenetic regulation. In other words, they help determine whether a gene is expressed or not. Among many other things, SCFA-mediated inhibition of these enzymes increases expression of thyroid receptors (16).
2. Take probiotics or eat fermented foods Despite the long-hypothesized link between gut microbes and thyroid function, there are few controlled studies in humans that have tried manipulating the gut microbiota to improve thyroid health. However, supplementation in broiler chickens with lactic acid bacteria has been shown to increase blood plasma thyroid hormones (17), and Lactobacillus reuteri supplementation specifically improved thyroid function in mice (18). Lactic acid bacteria are commonly found in fermented vegetables such as sauerkraut and kimchi and fermented dairy products like yogurt and kefir.
3. Get tested/treated for SIBO or intestinal pathogens While the jury is still out on whether thyroid problems cause SIBO or SIBO causes thyroid problems, it certainly doesn’t hurt to get tested, especially if you are experiencing bloating, abdominal discomfort, or other symptoms characteristic of an overgrowth or infection.
4. Take other steps to heal your gut Remove inflammatory foods, manage stress, and eat a nutrient-dense diet that includes plenty of gut-healing foods like bone broth. For some people, healing the gut may be sufficient to ameliorate thyroid symptoms.

Now I’d like to hear from you. Did you know about the connection between the microbiota and the thyroid? Have you noticed any improvement in your thyroid symptoms by eating a gut-healing diet? Share your experience in the comments section!

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 with IBS have a quality of life that is lower than people with type 2 diabetes and even end-stage kidney failure. I found that actually easy to believe having a lot of experience with IBS patients myself. It didn’t surprise me and yet it’s pretty remarkable when it’s phrased that way. Dr. Brown: I try and reassure my patients. A lot of them come in and they feel embarrassed of the fact that they were told they have a functional disease yet they're still miserable. And when we compare it to these other disease processes that sound very bad—CHF, congestive heart failure, arthritis, things like that, you can modify your life to adapt to that disease. The problem is, your intestines, once they're in control, you can't will it to not have diarrhea or to not bloat, to not pain. So it tends to own you, and that lack of control really wears on you and it’s almost like having chronic pain, and so I really empathize with my patients that have this as I know it’s very real and it’s linked to depression, it’s linked to all of those things. Chris Kresser: I think it’s the number two cause of missing work too, behind the common cold, so this is definitely a serious problem that really wreaks havoc on people’s lives, and I've seen that. I've seen patients with just a “simple IBS diagnosis” that have pain 9/10 and have taken several trips to the hospital because they thought they were having appendicitis, when it just turned out to be gas pain or something related to IBS. So it’s definitely ... it can be a serious problem. Dr. Brown: Oh, for sure, not just for the patient but on the overall cost to our healthcare dollars. They’ve estimated that over 30 billion dollars a year are actually attributed to irritable bowel syndrome. This includes the patient going to the emergency room, getting CAT scan after CAT scan, which we know isn’t good getting, other tests done, doctor shopping, having some frustration. You know, we’re seeing this a lot. I think that we have shown that now you can have this post-infectious IBS, which essentially is SIBO. We have a lot of our veterans coming back, 20 percent of those veterans who get sick in a foreign land come back and then they sort of get shuffled around, and we’re now showing that it’s probably bacterial overgrowth and they get very frustrated and that’s a huge cost on the overall healthcare system, and so there’s a lot more than just calling this as a functional disease. This affects people’s lives, it affects people’s work, and everything—their relationships, all of it.

Studies published on Atrantil

Chris Kresser: So tell us a little bit more about these papers. I think the first one was a clinical trial and the second one was a retrospective analysis. Dr. Brown: Yes. So we have this brief ... little bit of background on how we actually came up with these three ingredients. It’s always something that my patients want to know and it has kind of an interesting story. When we were looking at this, when we were doing research, I was writing on a dry erase board that ultimately methane was the answer and my research manager, Brandy Scott, she actually is a very bright woman. She was an attorney and then got her masters in political science, I said, “Look, Brandy, if we can figure out how to do to this, we could help a lot of these people with severe bloating.” She had been a policy writer for a senator in Iowa, and she went, “Holy cow, wait a minute. Back when I was doing some policy writing, they were trying to mandate how to decrease methane production in cattle.” She’s like, “I got a bunch papers on this on how to do it through food products” and that’s how it all started. So, that’s how we figured out that putting these ingredients would be the best combination on how to decrease methane. So that led to our first trial, which was a randomized trial. We’re just trying to have proof of concept on that, and we did a randomized trial, and that was published in the Journal of Gastroenterology and Hepatology in September 2015, and it was pretty remarkable. We ended up having bloating scores improving almost to 91 percent, constipation improved up to 77 percent, and we didn’t have a whole lot of side effects. So, we knew that we were really onto something really big, and that’s when I decided to put it to the test. As a clinical gastroenterologist, that’s pretty cool that it worked in a randomized trial, but we all know that randomized trials have their pros and cons. I just want to be able to treat these people who are frustrated coming in, so we did a retrospective study—right sort of people, 26 people that had failed everything else available. I mean, the worst of the worst, they had to have failed Amitiza, Linzess, GlycoLax, probiotics, and I'm a big Xifaxan writer, they had to have failed Xifaxan plus neomycin. So we took people that really were at their wits’ end, and shockingly, I gave you that paper there—or not shockingly I should say, that as we expected—they did equally as well. We had almost an 88 percent quality of life improvement. Bloating improved threefold. We had a threefold improvement ... I'm sorry, bloating improved fivefold, pain improved threefold, constipation improved three-fold. So, super-exciting in the sense that we felt like, “Wow! Now we finally have something that we can actually help some of these people!” Chris Kresser: Yeah, that is really exciting, and we’ve been using it in our practice and I've seen some good results so far. It’s pretty early in the game for us, so we don’t have as much experience yet, but we have definitely seen some improvement and I like the idea, as a functional medicine guy and someone who’s originally trained as an herbalist, before anything else, I'm definitely interested in botanical medicine, and I've seen the trial. There was one trial that compared the botanical protocol for SIBO with rifaximin, where the botanical protocol came out as performed as well or better than rifaximin with fewer side effects. And so, we have these amazing plant medicines available to us; we often forget about them. Dr. Brown: Exactly, and I think that was the one out of Pittsburgh there. Yeah, I saw that. The only problem with that one was there was no real regimen for which antibiotics combination to use, I mean, herbal antibiotic combination to use. But I love seeing that an academic center is at least trying it and that’s awesome because a lot of times—and I'm just now really kind of getting involved with my functional medicine society down here, I gave a lecture—I really believe that there is some sort of Venn diagram where we can put this all together. Think of IBS and SIBO in one circle, think of leaky gut in the other, and then think of diet in the third, right there in the middle is the sweet spot. And I had so much fun being in a room full of functional medicine doctors where I gave a 45-minute lecture and we ended up with a two-hour Q&A where half of it was me asking them questions and their experience and what they have success with. I really think that we’re heading in the right direction as far as gut health, bringing a lot of gastroenterologists and MDs, speaking with naturopaths, speaking with dieticians because everybody just wants people to get better. That’s the bottom line.

Clinical pearls for treating with Atrantil

Chris Kresser: Yeah, absolutely. So, a lot of, about 25 percent of my audience actually, are healthcare practitioners of some sort. So for their benefit and for the patients, I'm curious just to know some clinical pearls that you’ve discovered over the last year or longer. I'm not sure how long you were using it before it came available, but what would you tell patients or clinicians who are treating patients some things to be aware of in terms of Atrantil. Like, did the people typically get better right away, or is there a Herxheimer type reaction in a lot of patients where they get a little bit worse initially and have what some colloquially refer to as a “die-off” reaction? What should patients and clinicians expect in terms of using this treatment? Dr. Brown: Absolutely great question. I really kind of put these ... I put each patient into two different categories. There are the ones that have mild disease or intermittent disease and they're going to respond a little bit different, and then those are the ones that come to see me. And you probably get this a lot also, patients come to see you that you may be a second opinion person. Chris Kresser: Yeah. Dr. Brown: So by the time they come to see me, I'm really dealing with difficult people. So I'm going to start with that group first. What I have found is that depending on the bacterial load, really, we need to hit them hard and strong, just like we did in the original studies with Xifaxan, and that’s how I explain it to them. I said, I want you to do a course of this. I want you to take two capsules three times a day until you start feeling better, and clinically, I can say that now that we’ve been out for a full year, we’ve treated more than 40,000 people with this countrywide. We’re very open about having people contact us, give their experience. So we’ve sold 40,000 units in a little bit more than a year. We know that those people that have very, very tough-to-treat disease are really going to take 10 to 20 days to really start feeling better. So, 80 percent of those people are really going to start noticing that. Of those, I would say, and I warn all my patients about it, so I tell them that if they start feeling bad or start experiencing a die-off, that’s not necessarily a bad thing. I don’t want you stop. I want you to stick through it. I add a little bit of baby aspirin, which tends to help and they can get through it, and so they get very excited when they start to have that because they kind of feel like something’s happening. In my own practice, I never really saw that very much whenever I would treat people with Xifaxan if they have constipation, so that kind of explains why we’re not having that kind of success with that. So, of these people that do that, what I do is I have them take that course, they get through it and then we’re learning something that most of my patients, they taught me this, they just feel better if they sort of take it as a daily supplement. And the reason is, is that these are just polyphenol molecules. They are the molecules that our body really wants and they almost work like prebiotics then. Then, they go into your colon where the colon breaks them down and makes you feel better. So most of my patients do a course and then they just stay on it, and then as needed, go back up. So that’s really tough to treat. Now, the extreme to treat, it always makes it a tough day when I show up to clinic and somebody’s already holding my product and I'm like, “Oh no, that’s all I had.” Then, we sit down and talk and then we really start going through some different things. And that’s where I have a … I have a great nutritionist that I work with here and she helps me look at it, okay, maybe there’s some food products and things like that, so we do leak testing and things. And as we’re going through it, very surprisingly, I have had some of these patients come back to me and say, “Hey doc, you know what, I increased it to three three times a day and now I'm better.” So we know that there’s the dosing thing. This is a moving target. We’re new, we’re breaking ground, and so just because it doesn’t work, maybe we need to add something else, and I'm talking about the bell curve here way to the right, people that just are struggling with everything. I have treated people with both Xifaxan and Atrantil, I've tried putting people on erythromycin at night, and you know, I can maybe get another 10 percent out of it. And so as the type of doctor I am, I tend to just focus on those ones that don’t do well and I almost forget about this whole left of the bell curve that does absolutely awesome on an as-needed basis. So from a clinical standpoint, I actually have severe gluten intolerance, and when I take Atrantil with any type of bread products or gluten products, I have zero issues. Chris Kresser: Interesting. Dr. Brown: It’s really interesting, and so that is an angle why I have all these patients taking it as needed. The mechanism of action, I don’t know. I don’t know if we’re binding zonulin. I don’t know if it’s the hydrogen sink that works that way, but I actually have celiac patients that swear that they can, and I'm not telling anybody that has celiac to go out and try this, but they're the ones that actually say, “Yeah, there’s something else going on here,” and so that’s where we kind of where we start thinking of what else is going on, what’s the future of this. But for the clinicians in the audience, it’s two separate groups, main groups: the ones that need to take it periodically and then sort of take it as an overall digestive health; the ones that need a good round of treatment, 10 to 20 days, sometimes a little bit longer, and then that little subset that I'm going to ... well, basically, people like you and myself are trying to figure out, right? Those people that keep getting second opinions and that’s what I really like, when I get feedback from people and they say, “Hey, I took it with barberry and I had a better response.” “Oh, that’s awesome.” We’re trying to figure those stuff out. Chris Kresser: Yeah. Makes sense. Are there any typical symptoms in terms of a die-off reaction that, is there anything that’s typical, like, worsening of constipation or even diarrhea or gas or bloating, or does it just kind of run the gamut? Dr. Brown: I think it runs the gamut, but they will typically have whatever symptoms I tell them the die-off will cause. Chris Kresser: That’s the nocebo effect. Dr. Brown: Yeah. Chris Kresser: Very well documented, real deal. Dr. Brown: Yeah. I just want to go as, “If you do have this, it’s a die-off, you may notice some headaches, fever-like, and maybe increased bloating and constipation,” and then for sure it happens. So it’s kind of all over. Chris Kresser: Yeah. Dr. Brown: And very interesting, when we first launched one of my patients who was actually on a SIBO form and she said, “Hey, I took this and I got better,” so we jumped right into the most difficult group, great feedback from them. We have 100 percent money back guarantee, I just want to know why. How did you feel? What happened? Because we learn, it’s a learning process. And that particular group that was already on the forum had already failed everything. They kind of whittled themselves down to being really tough people. Those people gave us great feedback on the die-off reaction and what worked and what didn’t. And some of them tried Saccharomyces and that seemed to help a little bit, and some of them took the aspirin, so I love when my patients in the internet community give us feedback. We’re just trying to help people, is the bottom line. Chris Kresser: Absolutely. So what’s next? Do you have any other research projects going on or things you're thinking about for the future or just continuing that, kind of, learn more about Atrantil in this approach? Dr. Brown: Well, I think there are a couple of things. I’ve got my interests, and then of course, we do have still pay the lights to keep manufacturing Atrantil, so we’re actually working with some great doctors at Texas Tech right now and they are putting together a large multicenter study that we’re almost ready to start rolling in and we’re doing that just like it would be for any large pharmacological agent because as we start to bridge this gap between the natural products and pharmacologic products, I want to hold this up to the same standards. So that’s going to be third party. It’ll be done out of Texas Tech, they got some great guys over there. And when we start enrolling, we would love to have you enroll people and everything. Let’s do a large multicenter trial. The reason why it hasn’t been done before—people, whenever I talk, they’re like, “I’d like to see a larger trial.” I'm like, I would like to also except that much of this is just being funded by me and my colleagues—actually, everything is only funded by me and colleagues. You know, everything takes money and that’s why—it’s one of the reasons why we don’t have good studies on probiotics, for instance. Somebody has to foot the bill, and if you want to foot the bill and then risk having your particular probiotic combination not look good, well, you're out several hundred thousand dollars, you know, so— Chris Kresser: Yeah. It’s one thing for a pharmaceutical company to shove it in the file drawer, as they say, the file drawer phenomenon. It’s another— Dr. Brown: Exactly. Chris Kresser: Because you're a small company. So, thanks so much for taking the time to be with us, Dr. Brown. I'm really grateful that you took a risk and decided to make this product because I've had a similar experience to you where IBS-D and hydrogen-predominant SIBO are a lot easier, more straightforward to treat than methane-predominant SIBO, and so it’s really great to have another tool and arsenal not only for us at the California Center for Functional Medicine but all the clinicians on training in the ADAPT framework program and the future clinicians that I hope to train. So, I appreciate your work in this area. Dr. Brown: I do want to say one thing, and I appreciate what you’ve done also, the doctor’s tend to try and treat themselves, so I finally went as a patient to a colleague friend who is a functional medicine doctor and he recommended your book. Chris Kresser: Oh, cool. Dr. Brown: And this is actually before any of this took place, so I had to laugh, I'm like, okay, so I think that the future of autoimmune disease lies in diet and polyphenols and things like that. And looking over that, I need to order your book, and I'm going to do that and figure out what type of Paleo diet I need to be on. Chris Kresser: That’s right, cool. Well, thanks again, Dr. Brown. I look forward to more collaboration in the future. Definitely let us know about the new study because we have an enormous number of patients that we have treated and are treating for SIBO, so we would be definitely interested in participating. Dr. Brown: Absolutely. Thank you so much for your time. Chris Kresser: All right. Take care. Dr. Brown: Bye, Chris. Okay everyone, I hope you enjoyed that interview with Dr. Brown. If you’d like to try Atrantil, you can get it in my online store. As I've said, we’ve been using it at the California Center for Functional Medicine and had some really good results with some patients, so I definitely think it’s worth a try, and if it does work well for you, I agree with Dr. Brown that taking a lower maintenance dose over a long period of time or indefinitely, it may not be a bad idea especially because of the really high recurrence rates for SIBO. And studies have shown that it can recur anywhere between 40 and 60 percent and up of patients, depending on their particular presentation, and it’s a real challenge clinically to treat these patients because even when we’re successful in getting rid of SIBO, it’ll often come back. So I think having an option that’s just a simple combination of botanicals that patients can take over a long term rather than multiple courses of very expensive drugs that have potential side effects is a much better option in my opinion. So again, thanks for listening, I’ll see you next time. If you’d like to leave a question for me to answer in a future episode, you can do that at chriskresser.com/podcastquestion. You can also leave a suggestion for someone you’d like me to interview there. If you're in social media, you can follow me at twitter.com/chriskresser or facebook.com/chriskresserlac. I post a lot of articles and research that I do throughout the week there that never make it to the blogger podcast, so it’s a great way to stay abreast of the latest developments. Thanks so much for listening. I’ll talk to you next time.

In this episode we will discuss:

• Is lactulose breath testing an accurate way to diagnose SIBO?
• Is SIBO always pathological?
• Are our treatments effective?
• Is SIBO always the underlying cause?
• Should probiotics and prebiotics be avoided during treatment?
• Does a long-term low-FODMAP diet help prevent recurrence?

[smart_track_player url="http://traffic.libsyn.com/thehealthyskeptic/RHR_-_Unanswered_Questions_About_SIBO.mp3" title="RHR: Unanswered Questions About SIBO" artist="Chris Kresser" ] Hey, everybody, it’s Chris Kresser. Welcome to another episode of Revolution Health Radio. This week we're going to do something a little bit different. Rather than answer one specific question that was sent in, I'm going to answer a bunch of different questions that I get all the time regarding a very popular topic, which is SIBO. As a matter of fact, I have many questions about SIBO myself, and that's actually how I want to frame this podcast. I get more questions about SIBO than probably any other health topic. I've been treating it now for many years, and I've learned a lot about it in that time, and yet it seems like the more I learn, the more questions I have. Certainly, if you look on internet forums and blog comments, you look at summits and podcasts in our entire field, you can see that there's still a lot of questions about SIBO and misunderstanding and things that we really need to figure out in order to be able to appropriately diagnose and treat this condition. I think the best way to dive into this is just to say that I've started to doubt many of the standard assumptions or beliefs around SIBO that many of you are probably already aware of. I just want to go through five or six of these assumptions and tell you what my current thinking about them is, and this might be a little bit of a frustrating podcast to listen to because I'm not necessarily going to give you answers. I'm just going to tell you what the questions are, where my doubts are, and what further research or exploration or investigation I think we need to do.

Question #1: Is lactulose breath testing an accurate way to diagnose SIBO?

Let's start with assumption number one, which is that lactulose breath testing is an accurate way of diagnosing SIBO. As many of you know, the standard way of diagnosing SIBO in an outpatient setting is using lactulose breath testing. There is another way, which is an endoscopy, where they put a tube down your throat and take a sample of bacteria from your small intestine, but that's never used in outpatient settings because it's invasive and expensive. It's just not done. There are actually a lot of problems with that method as well, which leads us to probably the biggest issue of all from a 30,000-foot-view perspective with SIBO, is that in order for a test to be accurate, it needs to be validated against something that's a gold standard, and we have no gold standard way of diagnosing SIBO. The endoscopy, which I just mentioned, has been used as the gold standard test against which breath testing is validated. But what if the gold standard test itself is not accurate? That obviously creates some pretty big problems in terms of developing another test like breath testing and then validating it against a test that itself is not very valid. That's the biggest issue.

The problems with SIBO diagnosis and treatment

I'm not going to go into all the nitty-gritty details on why breath testing isn't necessarily as accurate as some people may believe. But in this context, I'll just say that—and this is a guess, I haven't done any rigorous study—but I would estimate that over 90 percent of the patients we test for SIBO test positive. Now this is using the former criteria and I'll come back to this in a second, but if you just use the machine-generated criteria that are printed on any of the SIBO breath testing labs, I would say over 90 percent of our patients test positive. Now, that alone should be a red flag. When more than 90 percent of your patients test positive for a condition, that should raise some eyebrows. Certainly SIBO is common, but do we really expect that 90 percent of patients, even people who are sick and dealing with chronic health issues have SIBO? I've never seen any research suggesting that over 90 percent of people with any particular conditions also have SIBO. The exception might be acne rosacea. I think I saw one study of 42 patients where 100 percent of patients with acne rosacea had SIBO [Correction: study I was referring to found that SIBO was 17 times more prevalent in patients with rosacea than in controls.] This doesn't mean for sure that the test is inaccurate, but it definitely raises my eyebrows. It makes me wonder whether we're over-diagnosing SIBO. Changes in criteria Now I mentioned the criteria, so up until pretty recently the idea was that if you see an increase in 20 parts per million or more of hydrogen in the first 120 minutes of the test, that would indicate a positive result, and the criteria were an increase in 12 parts per million for methane, but those criteria recently changed; there was a consensus statement issued in the spring. A bunch of SIBO experts got together and talked about how to update the breath-testing criteria to make it more accurate and ensure that the criteria were modified to, on the one hand with hydrogen, the changes would lead to fewer diagnoses, less overdiagnosis of hydrogen-predominant SIBO. But in the case of methane, they're going to lead to a greater number of diagnoses because those criteria, instead of becoming more strict, became more liberal. The new hydrogen criteria are increasing 20 parts per million within the first 90 minutes, and then with methane, it's any value over 10 parts per million at any point during the test, including during the third hour. That’s a pretty big difference, and that's going to lead to a lot more positive results for methane. It’s also worth pointing out that there are a lot of different studies that are critical of lactulose breath testing that suggest that there is a very high potential for false positives, especially using lactulose instead of glucose. With glucose breath testing, the opposite problem is true. There's a high potential for false negatives. If there is a positive, it should be positive. But if there's a negative, you can't rule out that SIBO might be present. Again, I'm not going to go into great detail here, but let's just say that there is a lot of uncertainty about breath testing as a way of diagnosing SIBO.

Question #2: Is SIBO always pathological?

The second assumption is that SIBO is always pathological. The idea is that if SIBO is present, it's always causing the patient's problems, whatever they are, but that's not sound thinking, of course, because we know that correlation is not causation. It's possible that SIBO could be present, but it's not actually driving whatever the patient's symptoms are. We know that early studies suggested that up to 20 to 30 percent of healthy controls have SIBO but don't have symptoms. Of course, I have to offer a side note here, which is, I don't know where these studies are finding these so-called “very healthy controls with no symptoms.” I haven't met that many of those people, but let's assume that that's true. That could mean that 20 to 30 percent of the population has SIBO, but it's not causing any problems for them. In many cases, we treat SIBO, and the numbers improve, so the patient goes from being breath-test positive to breath-test negative, but their symptoms don't necessarily improve. That would suggest that maybe SIBO was present, but it wasn't causing their symptoms. It's possible that the testing is accurate as far as what it's measuring, but what we call SIBO as a condition is not always pathological. It's also possible that SIBO might be present in a patient and might be causing some issues, maybe a mild nutrient deficiency or something like that, but it's not causing the main complaints. The reason I bring this up is that I see some patients just getting hyperfocused, almost obsessed about SIBO, at the expense of everything else. And clinicians—there is that saying, “If you've got a hammer, everything looks like a nail”—I see both clinicians and patients becoming over-focused, I think, on SIBO, and the risk there is that you actually miss other pathologies or underlying mechanisms that are really actually driving the condition in those cases if we're just myopically focused on SIBO.

Question #3: Are our treatments effective?

The third assumption is that our current treatments are effective and optimal. The typical treatments for SIBO are antimicrobials. Initially, there were prescription medications. Rifaximin is the most commonly used, especially for hydrogen-predominant SIBO, and neomycin is also added at times when methane is present. Metronidazole is another medication, or Flagyl is used in some cases for treating SIBO, as well as other antibiotics, but rifaximin certainly has become the drug of choice. But then there have been some studies recently that have found that botanicals, herbs, are as effective as rifaximin treatment or even more effective and cause fewer side effects. In general, the approach is if SIBO is there, then you use antimicrobials to reduce the growth of bacteria in the small intestine. The problem with this approach is that the efficacy is often quite low. I've seen some studies that we use rifaximin individually that show as low as 40 percent efficacy. Of course, there are other studies that show higher efficacy, and then if you combine other agents in the treatment, you can make it more effective. There was one treatment where the researchers speculated that using partially hydrolyzed guar gum would improve the efficacy of rifaximin, and in fact it did. It increased it significantly. In our clinic we use a combination protocol that uses a bunch of different things together, all of which are designed to maximize the efficacy. It also depends whether it's just hydrogen alone that's high, or methane alone that's high, or both hydrogen and methane, and each of those scenarios requires a different approach. But the problem remains that efficacy is much lower than I certainly would like to see it. Not only that, in some cases, not only do patients not get better, they actually get worse after treatment. They might get worse right away or they might improve initially, but then the symptoms return and when they come back, they come back even worse. I've seen this actually happen in multiple cycles, meaning with each treatment and each return of symptoms, the symptoms get worse after each cycle, which is obviously problematic. Then there's the very high rates of recurrence for SIBO, which is related to what I just said. One study, I think, found a recurrence rate of 45 percent in patients who had been treated by rifaximin. In our practice, despite using all of the evidence-based methods and combining several different methods, we still see recurrence rates a lot higher than optimal, than I think is acceptable. That's one of the main things that has led me to question many of these beliefs and assumptions because when the treatments are not that effective and the recurrence rates are very high, then I think that something is definitely wrong.

Question #4: Is SIBO always the underlying cause?

The fourth assumption is that SIBO was always the underlying cause of a particular condition. This is somewhat related to what I mentioned earlier, but a little bit different. In functional medicine, we're always trying to get to the root of the problem, but sometimes that's easier said than done, and it can be like peeling layers of an onion back to keep going deeper to find the deepest underlying issue. If a patient has SIBO, for example, and we treat their SIBO and it doesn't go away, or maybe it does go away and it comes back, and we do that two or three times, then of course I start wondering, “All right. Well, is there some other deeper condition that is causing the SIBO?” In this case SIBO is not necessarily a cause itself, but almost a symptom of a deeper underlying problem. In my experience, those problems can be things like:

• mold or chronic inflammatory response syndrome
• chronic infections like tick-borne illnesses
• viral reactivation
• other gut infections that have escaped detection
• heavy metal toxicity
• other types of toxicity
• mitochondrial deficiency

And a range of other problems. But the point being that in those cases, those problems are the real thing that's driving SIBO and then whatever symptoms the SIBO is causing. It’s like layers, and so you have to keep going deeper in order to identify and address those conditions, otherwise that patient is never going to get over SIBO. We’ll just keep treating it, it might improve a little bit or not, and then it just keeps coming back. Even though rifaximin and the botanicals are relatively safe compared to other antimicrobials, they're still antimicrobials, and we still want to minimize our use of them.

Question #5: Should probiotics and prebiotics be avoided during treatment?

Assumption number five is that probiotics and prebiotics should always be avoided when a patient has SIBO and shouldn't be included in treatment. I think I've discussed this before and I'm not totally sure where this belief or assumption came from. It's pretty prevalent within the mainstream SIBO community, if you want to call it that. But all of the studies that I've seen, I think, without exception, have found that when you use probiotics, either along with antibiotics or as separate distinct treatment for SIBO, they are effective. They're either effective as solo treatment, or they increase the efficacy of SIBO [treatment protocols]. Even the studies that have used probiotics have shown positive results, which might be a little counterintuitive because you would expect probiotics to feed the bacteria that are present in the small intestine. I think there are still quite a few questions here. Certainly, I have seen probiotics, and probiotics make patients with SIBO worse, but in other cases, I've seen them make patients with SIBO significantly better. We do include very specific types of probiotics and even prebiotics in our SIBO treatment protocol. We've done that for many years because of the research I've seen on this, and I do think it is effective in most cases. This sort of points to another question or concept, which historically a lot of SIBO authorities have claimed that SIBO is just really kind of a small intestine, it's not really related to the health of the large intestine or the overall gut microbiome. That doesn't make sense to me. There is a sphincter that separates the small and large intestine, but one of the prevailing theories about how SIBO got started in the first place is it’s an inappropriate transfer of bacteria from the large intestine to the small intestine. It's entirely possible, and even likely, in my opinion, that one of the predisposing factors that can lead to that translocation of bacteria from the large intestine to the small intestine is an unhealthy large intestine. It may be that that’s one of the reasons that prebiotics and probiotics work in terms of treating and even preventing recurrence of SIBO is that they help to improve the gut microbiome. That, in turn, has a sort of upstream effect on the small intestine. Really, still a lot of unanswered questions here related to probiotics and probiotics, but I've seen enough now to convince me that the dominant idea that they should always be avoided is not true.

Question #6: Does a long-term low-FODMAP diet help prevent recurrence?

Then finally, the last assumption, number six, is that a long-term low-FODMAP diet is always a good idea in order to prevent recurrence. I have discussed this and written about this before, so I'm just going to mention it briefly. But studies have shown that a long-term low-FODMAP diet can reduce the diversity and quality of beneficial bacteria in the large intestine, and for the reasons that I just mentioned, I think that that can be problematic. Even though the low-FODMAP diet can reduce symptoms, it may be setting patients up for recurrence if it's leading to undesirable changes in the beneficial bacteria in the colon. Also, there was a recent study that just came out that found that patients with IBS are often able to reintroduce certain FODMAPs without any adverse effects. This study didn't consider SIBO, but as you probably know, many patients with IBS do have SIBO. My guess is that they would have found a similar effect if they had done the study in patients that only had SIBO. It seems that even in patients who do have SIBO or IBS that reintroducing some FODMAPs not only could be potentially beneficial, but doesn't actually lead to a return of symptoms. That's what I've always encouraged my patients to do is reintroduce as many FODMAPs as they can without significant discomfort. I think that's a wise approach because we want to keep our diet as diverse as possible, and especially when it comes to fermentable fiber, it can support our beneficial gut bacteria. Okay. I'm going to stop there. As you can see again, this is a little frustrating maybe to listen to. I'll tell you that it's super frustrating for me as a clinician. This is again something I've been paying very close attention to for a long period of time, and I feel quite frustrated with the lack of answers around many of these questions. Certainly, not for lack of looking, experimenting, and exploring, but my commitment to you is that I will continue to do that. I think it's a very important starting place to just admit when we don't know the answers to these questions at least, and to lay those questions out so we can start exploring what the answers might be, and of course that is the process of science. It's not that we always have the answers and we always know what and we stop looking. Once we think we know the answers, we always question our assumptions and we continually re-evaluate them, especially in the face of evidence that contradicts our previous assumptions or beliefs. That's the true application of the scientific method in the case of healthcare. I hope that was helpful in some way. If you're a patient out there and you're frustrated with your lack of progress with SIBO, you're definitely not alone. If you're a clinician out there and you're frustrated with your lack of progress with SIBO in terms of treating patients, you're definitely not alone. I think we should ... we need to get these questions out there more so that we can all work together to answer them. Okay, that's it for now. Please continue to send your questions in at chriskresser.com/podcastquestion, and I'll talk to you next time. Take care, everybody.

Fibromyalgia is a disorder that causes muscle pain and fatigue. People with fibromyalgia often experience tenderness at certain points on their body when pressure is applied. Fibromyalgia sufferers also experience other symptoms, including:

• Insomnia or difficulty sleeping
• Morning stiffness
• Headaches
• Numbness or tingling in the hands and feet
• Menstrual irregularities and pain
• Difficulty concentrating (i.e. “brain fog”)

According to the most recent statistics, about five million Americans (roughly 1 in 50) suffer from fibromyalgia. It’s the second most common musculoskeletal ailment behind arthritis, and it affects females far more often than males (it is seven times more common in women). As anyone with fibromyalgia will tell you, it’s a debilitating condition that affects every aspect of life. For example:

• People with fibromyalgia are three to four times more likely to suffer from depression.
• 50% of fibromyalgia sufferers have difficulty performing daily activities.
• 30–40% of people with fibromyalgia have to quit work or change jobs.
• People with fibromyalgia are hospitalized once every three years on average.
• The average fibromyalgia patient uses three or four drugs daily to control symptoms.

What is the conventional approach to fibromyalgia?

There is no laboratory test to diagnose fibromyalgia. Instead, patients are diagnosed based on their symptoms and history, and after excluding other diseases that may present with similar symptoms, such as rheumatoid arthritis, major depressive disorder, multiple sclerosis, and other autoimmune diseases. There is no consensus in the medical community on what causes fibromyalgia. However, the current theory is that it may involve a variety of factors, including:

• Genetics. Fibromyalgia runs in families, so there may be genetic mutations that make people more susceptible to it.
• Infections. Some viral or bacterial infections appear to trigger or aggravate fibromyalgia.
• Physical or emotional trauma. Post-traumatic stress disorder has been linked to fibromyalgia.

Because the cause of fibromyalgia is unknown, conventional treatment is focused on managing symptoms. Common medications prescribed include analgesics (OTC pain relievers like ibuprofen, or prescription drugs like tramadol), antidepressants, and anti-seizure drugs (which are sometimes helpful in reducing certain types of pain).

An alternative theory on what causes fibromyalgia

For many years I’ve suspected that fibromyalgia is caused by gut dysfunction. I noticed that the vast majority of my patients with fibromyalgia also had digestive problems, and when I started to run tests on them, I discovered that many of them had gut infections, dysbiosis, small intestinal bacterial overgrowth (SIBO), and leaky gut.

Could an unhealthy gut be the cause of fibromyalgia?

Then I decided to look into whether this connection had been explored in the scientific literature. Sure enough, there were several studies connecting fibromyalgia with problems in the gut. For example:

• 73% of patients with fibromyalgia reported GI symptoms, compared with 37% of those with osteoarthritis. (1)
• Irritable Bowel Syndrome (IBS) is present in 30–70% of fibromyalgia patients. (2)
• 33% of IBS patients meet the diagnostic criteria for fibromyalgia, compared to just 4% of control subjects. (3)
• Up to 50% of patients with fibromyalgia have functional dyspepsia, which is a fancy term for “indigestion” with no known cause. (4)

While I was intrigued by these correlations, they are just that—correlations. What’s more, like fibromyalgia, IBS and functional dyspepsia are simply diagnoses based on symptoms, so these papers didn’t shed much light on what actually might be causing both the fibromyalgia and the IBS/indigestion. In functional medicine, we’re always concerned with finding the underlying mechanism or cause, because addressing that is what will lead to the most effective and long-lasting treatment. So I kept digging through the research, and I hit the jackpot. I found several papers associating fibromyalgia with specific mechanisms of gut dysfunction. For example:

• A study in 2008 found a relationship between alterations of the intestinal microbiota (i.e. “gut flora”) and fibromyalgia. (5)
• Researchers at Cedars-Sinai Medical Center in Los Angeles found that 100% (42/42) of fibromyalgia patients they studied had small intestinal bacterial overgrowth (SIBO). This is astounding. (6)
• A study of 40 patients with fibromyalgia, 28 (70%) had intestinal permeability (i.e. leaky gut). Importantly, 12 of the 28 patients with leaky gut had no gut symptoms. I believe this is one reason the gut is often overlooked as a potential underlying cause of fibromyalgia. (7)

Are gut problems the cause—or effect—of fibromyalgia?

Of course, one might ask “Are these gut problems causing fibromyalgia, or is it the other way around?” At least one study has directly addressed this question. A group of patients with fibromyalgia that were positive for SIBO were split into two groups. One group received antibiotics to treat the SIBO, and the other group received a placebo. Significant improvement of fibromyalgia symptoms was observed in the patients that achieved eradication of SIBO with antibiotics, whereas no improvement was seen in patients who took placebo or who still tested positive for SIBO after the antibiotics. (8) This suggests that SIBO plays a causal role in fibromyalgia for at least some patients.

A new approach to treating fibromyalgia

If GI problems such as SIBO, dysbiosis, infections, and leaky gut are the underlying cause of fibromyalgia, it follows that healing the gut is the key to long-term improvement for fibromyalgia sufferers. I’ve written extensively about how to do that elsewhere on my blog (this free eBook on gut health is a great place to start), but here’s a brief summary of the most important steps:

• Avoid foods, medications (e.g. antibiotics), and chemicals (e.g. BPA) that irritate the gut.
• Eat plenty of fermentable fibers (starches like sweet potato, yam, yucca, etc.).
• Eat fermented foods like kefir, yogurt, sauerkraut, kim chi, etc..
• Consume bone broth and glycine-rich foods (e.g. tougher cuts of meat like beef shanks, oxtail, brisket, and chuck roast).
• Consider taking a probiotic (I prefer soil-based organisms like Prescript Assist) and/or a prebiotic supplement (like PreBiogen).
• Treat any intestinal pathogens (such as parasites) that may be present.
• Manage your stress (with mediation, mindfulness practice, biofeedback, etc.).
• Get at least 7–8 hours of sleep each night.

Now I’d like to hear from you. Have you been diagnosed with fibromyalgia? If so, do you also have digestive problems? Have you noticed any improvement in your fibromyalgia symptoms after taking steps to heal your gut? Please share your experience in the comments section.

A lot of people might not be familiar with the term methanogen, but it is something that people should be aware of, especially if you have SIBO or suspect you may have SIBO.  We’ve talked about SIBO a lot.  For people new to the show or new to this work, this stands for small intestinal bacterial overgrowth.  It’s defined as a pathological increase in bacteria in the small bowel.  As a reminder, we have a lot of bacteria in our gut.  In fact, the bacteria and other organisms in our gut outnumber human cells by 10 to 1, but the location of that bacteria is really important.  In this episode, we cover: 1:29 What Chris had for breakfast 4:44 The role archaea play in gut health 7:50 What's the big deal about methane? 14:38 How to address SIBO in methane-producing patients 23:56 Gut healthy treatment recommendations [powerpress] Jordan Reasoner:  Hi.  Welcome to another episode of the Revolution Health Radio show.  The show is brought to you by ChrisKresser.com.  Steve is off today on a meditation retreat.  I’m your guest host Jordan Reasoner, from SCDlifestyle.com.  With me is integrative medical practitioner, healthy skeptic, and New York Times bestselling author, Chris Kresser.  Chris, welcome. Chris Kresser:  Jordan, I’m happy you’re here.  And I’m happy Steve’s off walking the talk.  It will be interesting to hear about his experience when he gets back. Jordan Reasoner:  I’m excited.  He’ll be back tomorrow, so I’m looking forward to it. Chris Kresser:  This was his first 10-day Vipassana, is that right? Jordan Reasoner:  Yeah, it’s his first one. Chris Kresser:  It should be really interesting to hear about. Jordan Reasoner:  All of our friends are just coming back from Burning Man, and Steve’s coming back from a meditation retreat. Chris Kresser:  Yeah, other side of the spectrum.  Hopefully, you haven’t been getting any text messages from him in the last 10 days. Jordan Reasoner:  No.  It’s been radio silence. Chris Kresser:  Good, good. Jordan Reasoner:  So he’s been a good boy. Chris Kresser:  All right.  Cool. Jordan Reasoner:  Before we dive in, let’s talk about your breakfast, because I know we always get a lot of flak from the listeners if you don’t tell us about your breakfast, right?

What Chris ate for breakfast

Chris Kresser:  Okay.  So let’s see, I had some chorizo. We buy half a pig from a local rancher a couple of times a year, and then a butcher in Santa Rosa, Willowside Meats, butchers it and gives us a whole bunch of different cuts.  One of the things they do is make this really amazing chorizo.  So we had some of that, some scrambled eggs, some sauerkraut, beet kvass, and some plantains fried in expeller-pressed coconut oil.  That’s pretty standard breakfast around here.  It’s a good one.  Sylvie loves it.  We all like it.  It’s pretty easy to make. Jordan Reasoner:  I love your breakfast because it always has like five to seven parts to it. Chris Kresser:  It’s all about the diversity, right? Jordan Reasoner:  Yeah, exactly. Chris Kresser:  Feed those gut bugs. Jordan Reasoner:  You grew up on Lucky Charms.  It’s a nice transition, right? Chris Kresser:  Thankfully, I didn’t grow up on Lucky Charms.  As I get older, I have more and more appreciation for my parents, and the way that my mom fed us when we were young.  I mean, certainly, she wasn’t feeding us Paleo.  That wasn’t really part of the understanding at that point.  But she fed us, really, a pretty healthy diet overall, so I’m happy about that.  We have a good question today from Simas I think it is.  I’m not sure how to pronounce it, but I think that’s the right way.  Let’s give it a listen. Simas:  Hi, Chris.  I just wanted to ask, what would be the best way to deal with methanogens in people with SIBO?  I know Dr. Siebecker says that it’s best to use allicin, but it seems that I have a negative response, extreme fatigue and things like that, after taking it.  Thanks. Chris Kresser:  All right.  So let’s jump in here.  That’s a great question.  A lot of people might not be familiar with the term methanogen, but it is something that people should be aware of, especially if you have SIBO or suspect you may have SIBO.  We’ve talked about SIBO a lot.  For people new to the show or new to this work, this stands for small intestinal bacterial overgrowth.  It’s defined as a pathological increase in bacteria in the small bowel.  As a reminder, we have a lot of bacteria in our gut.  In fact, the bacteria and other organisms in our gut outnumber human cells by 10 to 1, but the location of that bacteria is really important.  They should mostly be in the colon, the large intestine.  We do have small amounts of bacteria all the way through the digestive tract, from the mouth to the anus, but the majority of the bacteria should be in the colon.  Very little should be in the small intestine, because the small intestine is where we digest and absorb food.  If you have a lot of bacteria growing in the small intestine, that’s going to interfere with the assimilation of nutrients from food, which is one of the major adverse effects of SIBO.

The role archaea play in gut health

So most of the research that you’ve probably heard about has focused on the role of bacteria in the gut, but recent evidence suggests that archaea also play a role.  That’s A-R-C-H-A-E-A.  Archaea are actually a completely different class of organism than bacteria.  They’re pretty ancient, single-celled organisms with no cell nucleus and no membrane-bound organelles.  They were originally classified as bacteria, but they’re now classified as prokaryotes, which again are a completely different class.  They’re considered totally unique from the other two major domains of life, which are bacteria and eukaryotes.  Some of the archaea that you might have heard of in the news, in the mainstream media are halophiles and thermophiles.  So these are archaea that live in extreme environments like salt lakes or hot springs.  But we now know that archaea are present in pretty much every habitat where you see biodegradation of organic compounds occurring, and that includes animal guts and human guts. When you go to get a breath test for SIBO—which is one of the major ways of testing for SIBO that we talked about—they’re going to measure the presence of, and the production of, methane and hydrogen gases at baseline.  Then they’re also going to measure the increase in hydrogen and methane production that occurs after you drink a sugary solution that they give you as part of the test procedure.  So typically, if you have a significant increase in hydrogen or methane after drinking the sugary solution, it means you have an overgrowth of bacteria in your gut.  To be more specific, when you have an increase in methane after drinking this solution, or if you just have high levels of methane at baseline, that indicates an overgrowth not of bacteria, but of these methane-producing archaea.  Unlike bacteria, which primarily produce hydrogen, the archaea are what produce this methane, and they do this actually not by fermenting carbohydrates.  So bacteria produce hydrogen and the way they do that is by fermenting fibers.  The methane production works differently.  The archaea consume the hydrogen that’s produced by the hydrogen-producing bacteria, and then they produce methane as a by-product of that process.  So this is actually one of the ways that excess hydrogen in the gut gets metabolized, is by these methanogenic archaea converting that hydrogen into methane.  And another way that hydrogen gets dealt with is by bacteria that convert hydrogen into sulfites.  That’s probably a little more detail than you needed, but it’s kind of interesting to see how this all works.

What's the big deal about methane?

Methane production begins at about three years of age.  You don’t see any methane production in infants, for example.  This suggests that methane production has everything to do with how the gut is colonized initially, because there are no archaea initially in the gut.  And it peaks at about 10 years of age, when adult levels are reached.  So by the time a child is 10, they’re typically producing the adult amounts of methane that they would produce for their whole life.  But here’s the thing—not everybody produces methane.  Depending on the studies that you look at, the numbers I’ve seen range from 30 percent to 50 percent of adults being methane producers.  So anywhere from a third to half of people have significant amounts of archaea that produce detectible amounts of methane.  That’s something important to understand—this is not an issue that affects everybody. So what’s the big deal about methane?  Simas’s question, “Is the presence of methane different?  Does it require a different approach?”  I think the answer is yes.  For what we see in the research and then what I’ve seen in my clinical experience working with patients.  Methane is a colorless, odorless, inert gas.  For a long time, it was thought that it didn’t really have any impact on human health, except for maybe causing a little bit of bloating and distention, if you had high levels of it.  But more recent evidence actually has linked methane production to various disease states.  And it’s still somewhat unclear whether that’s because of the level of methane itself, or whether it’s because of the removal of hydrogen from the bowel that happens when that hydrogen is converted to methane by archaea.  But we do know from studies that methane-producing archaea are present in 45 percent of people with SIBO.  In other words, a substantial percentage of people with SIBO have methane-producing archaea.  And the amount of methane that’s produced is significantly higher in patients with SIBO, compared with patients with fructose and lactose malabsorption, which are other gut issues.  So if you’re looking at a breath test, the presence of methane, to consider yourself a methane producer, you would have baseline methane levels of over 3 parts per million.  And I can tell you, from running a lot of these tests, that that’s quite common.  It’s more than 50 percent, I would say, in my patient population.  Then again, I’m testing people that mostly have SIBO and other gut issues, so it’s not necessarily a representative sample. Jordan Reasoner:  Now Chris, if I’m a patient and I’m experiencing problems, I think it’s SIBO and I’m not looking at a test, are there symptoms that are different in somebody who is predominantly going to have methane-producing bacteria versus non-methane-producing? Chris Kresser:  Yeah.  That’s a good question.  And it takes us right into the next section, which is, the answer to that is constipation.  Constipation, of course, can be caused by many things.  So it’s not to say that methane-producing archaea are the only cause of constipation.  But methanogenic flora, or archaea that produce methane, are significantly associated with chronic constipation in the scientific literature.  The amount of methane produced is correlated with colonic transit time.  So the more methane you have, the slower your transit time is.  In one study, if a breath test was positive for methane, they saw a 100 percent association with constipation-predominant IBS. Jordan Reasoner: Wow. Chris Kresser:  So yeah, it’s pretty strong in terms of association.  In other words, to put it in plain language, everyone who is positive for methane had constipation-predominant IBS in that study.  In contrast, the prevalence of methane was very low among patients with inflammatory bowel diseases like Crohn’s and ulcerative colitis, which typically present with diarrhea.  So you see that it’s much more common in people with constipation than it is in people with diarrhea.  I’ve also seen this correlation in my work with patients, people who have the really chronic, intractable constipation that doesn’t tend to respond well to a lot of different interventions.  I will often see really high baseline levels of methane and/or an increase in methane production after the challenge test.  A few other things you’ll see clinically are methane producers can have a higher prevalence of rectal hypersensitivity compared to non-methane-producing patients.  So sometimes, pain in that area or just a feeling of urgency can signal methane production.  This is not something that patients will be aware of, but if you’re looking at test results in constipated patients, the average pH of the colon will be significantly lower in patients with methane-producing flora.  So if you see a low pH on a stool test, it might be one potential sign of methane production.  Also, I think the other thing that’s important to know is that methane production seems to be much more common in women than it is in men.  That’s the only real demographic characteristic I’ve been able to find.  It seems there’s no age-specific distribution, other than the fact that you don’t get methane production until three years of age, as I mentioned before, and it will be lower in kids up to 10 years of age typically.  But other than that, the only significant association I found is that it’s more common in women than it is in men. Jordan Reasoner:  In your research, have you seen any associations between being breastfed or vaginal birth versus C-section?  Have you seen any associations around that? Chris Kresser:  No, I haven’t.  I don’t think that that means there aren’t any, but there are only a handful of studies on this topic.  Most of them are pretty recent; most of them were done by Dr. Mark Pimentel’s group.  He, as many people know, has been a pioneer in research on SIBO and has a research clinic at Cedars-Sinai down in LA.  It does a lot of great work.  So I think there’s still a lot to be learned about this.  My guess is there is possibly an association, Jordan, but we don’t really know for sure about that.

How to address SIBO in methane-producing patients

Jordan Reasoner:  Chris, before we move on, what do I do about this in general?  If I’m somebody who, I find with a practitioner that I have more of these methane gases in my body, and I’m that type of a person with small intestinal bacterial overgrowth, how does that change your approach as a practitioner?  And how does that change what I do, as somebody who’s trying to recover from this? Chris Kresser:  So it could change the medications that you take for SIBO, if you are going to take medications, and may change the way you treat it overall.  The first thing, taking even a step back before we get into that, is to determine—so far, we’ve been talking about associations between methane and constipation, but that doesn’t necessarily tell us that methane is causing the constipation.  It could be that constipation is causing the high methane levels.  There is actually some research that suggests that might be true.  There are studies showing that treatment with laxatives and bowel cleansing, like a colonic, can reduce or eliminate methane production in some patients.  So that would suggest that constipation, at least to some extent, may increase—methanogens may favor a slow transit type of environment, and when you’re constipated, you might get an increase in methane-producing species. However, there are also a lot of other studies that suggests that methane directly causes the constipation in the first place.  For example, in animal models, they directly infuse methane into the small intestine.  You’ll see a reduction in transit time of 60 percent, compared to just infusing normal room air.  They suspect, right now, that this effect may be mediated by serotonin, which is a neurotransmitter—as I’m sure most people know—that is present in the gut in about 400-fold higher concentrations than is present in the brain.  So serotonin really, more than anything else, is a gut neurotransmitter, and it’s thought to affect intestinal motility.  Studies have found that methane producers have lower post-meal serotonin levels than people who produce primarily hydrogen.  So I think it is pretty reasonable to assume that methane does play a causative role in constipation.  Then there are also studies that show that the elimination of methane in treatment correlates very closely with symptom improvement.  That’s where your question comes in, Jordan.  So if you treat SIBO and you don’t address the methane production, even if you get rid of the hydrogen, the patient is probably not going to improve to the extent that they should, because you’re not getting rid of the methane. So here’s the tricky thing—rifaximin, which is the drug that is typically used to treat SIBO, is not very effective against methane-producing species on its own.  For example, in a study with patients who all had baseline levels of methane above 3 parts per million—which established them as methane producers—10 days of rifaximin alone led to a clinical response about 56 percent of the time, so roughly half the time.  But it only led to a negative result on the breath test 28 percent of the time.  So about 70 perecent of the time, rifaximin was not clearing the methane from the breath test, and about half the time, it wasn’t leading to any clinical improvement at all.  Now, 10 days of another drug that’s often used to treat SIBO on its own, called neomycin, led to a clinical improvement in 63 percent of cases, which is a little bit better than rifaximin on its own.  And it led to a negative breath test result 33 percent of the time, which is again, a little bit better than 28 percent for rifaximin.  But it’s not great, right?  We’re still talking about two-thirds of the time that it’s not working.  But if you combine rifaximin with neomycin together and take them for 10 days, that led to a clinical improvement 85 percent of the time, and a negative breath test result 87 percent of the time.  So now we’re talking about some real treatment efficacy numbers here.  Actually, they don’t really understand why the combo of rifaximin and neomycin works better than either of these two drugs alone, but there are other examples where this happens.  For example, the H. pylori treatment, right?  That requires two different antibiotics, and if you use one alone, or the other alone, you don’t get the same efficacy than if you use the two antibiotics together.  So there is a precedent for this kind of thing happening. The other thing to be aware of is that outside of rifaximin and neomycin, most methanogenic archaea are resistant to the majority of the antibiotics that are typically used against gram-positive and gram-negative bacteria.  So your ciprofloxacins and Flagyls and things like that that a lot of practitioners would use to clear out bacterial infection are probably not going to work for these types of archaea.  And in my mind, this is another reason why botanical treatments can really make a lot of sense.  We talked on a previous show about a study that showed that botanical treatments were as effective, or more effective, than antibiotics for SIBO, and had far fewer side effects.  One of the reasons for this is that botanicals, herbs, plant substances, have a really broad spectrum of activity.  And it’s far less likely that organisms will be able to develop resistance against a botanical, because within each single herb, there are many different active compounds, instead of just one active compound that’s in an antibiotic.  So it’s much harder for the organism to adapt to that.  And typically, herbs or botanicals are used in formulas, where you have many different herbs together.  You’ve got many different herbs, each with multiple compounds, and then they form together to create synergistic compounds.  It starts to become exponentially more diverse, complex, and more difficult for organisms to develop resistance to.  I think given some of the research we have on the efficacy of botanical treatments, given the increasing problem of antibiotic resistance, and possibly these archaea developing resistance to rifaximin and neomycin eventually, given the fact that studies show that about one out of two people who have SIBO and are treated successfully for it will relapse in the future, which is kind of a depressing statistic. Jordan Reasoner:  Yeah. Chris Kresser:  I mean, not to get too far off on a tangent, but I bet a lot of people in those studies aren’t doing low-FODMAP, Paleo type of diets or SCD type of diets.  They’re only just taking the drugs, and then they’re going back to eating the same crappy diet that led to the problem in the first place.  In my population, the relapse rates are not that high.  But given all that stuff, it’s possible that people will have to get treated more than once.  That’s what I’m getting at.  And I’m much more comfortable with the idea of someone doing multiple botanical protocols and using probiotics that secrete antimicrobial peptides—which probably may work against methanogens—and food-based treatments, like removing FODMAPs, which are the certain class of carbohydrates that feed the bacteria which produce hydrogen, which feed the archaea.  So if you starve the bacteria, you’re reducing the hydrogen levels.  That, in theory, would reduce the levels of substrate that are available to the archaea for producing the methane.  So the food-based treatments still work there.  I did mention, when we talked about the causal relationship with methane, that some studies show that a bowel lavage, a colonic, or a laxative kind of thing, can lower or even eliminate methane production.  But I would be careful with that, because colonics, while they do wash out some of the bad gut flora, they also wash out a lot of the good gut flora.  They’re also pretty invasive.  I think it’s probably best to try to treat with herbs, diet, and other antimicrobial nutrients than it is to use laxatives or colonics. Jordan Reasoner:  One of the common objections that I always hear with somebody that follows Dr. Pimentel’s work, they’re very familiar with this type of thing, and they’re going to end up on this combo of neomycin or rifaximin, people freeze.  That’s because we’re all really afraid to use antibiotics now almost in this health community, right? Chris Kresser:  Mm-hmm. Jordan Reasoner:  One of the most common things I get asked is, “What can I do before, during, and after this protocol to not totally set me back and destroy all my good gut flora?”

Gut healthy treatment recommendations

Chris Kresser:  That’s a valid question.  The good news is that rifaximin and neomycin are narrower in spectrum than ciprofloxacin or some of the really broad-spectrum antibiotics, and they’re not going to wipe out your gut flora to the extent that some of those other antibiotics will.  They’re also not absorbed systemically, that’s another advantage to those drugs.  I think rifaximin, 99.8 percent stays in your gut and doesn’t get absorbed, so it’s not going to affect flora in other parts of your body as much.  So they are safer than a lot of other antibiotics. My strategy is to start with the botanical protocols, and use antimicrobial botanicals like olive leaf extract, uva ursi, cat’s claw, yerba mansa, coptis, artemesia, sida, et cetera.  Then use soil-based organisms that secrete antimicrobial peptides—Prescript-Assist, which I sell in my store.  It’s available in my store, because I’ve just had such great success with it in just about everybody, which is rare with probiotics.  You know, a lot of people don’t respond to probiotics very well.  Then we have nutrients like Lauricidin or lauric acid, which are antimicrobial, which may be helpful in this kind of situation.  So I like to start a protocol with a whole bunch of natural things like that, and see how they do.  I only really recommend the rifaximin and neomycin combo if a couple of rounds of this initial protocol aren’t successful.  Then I would definitely suggest patients take things like Saccharomyces boulardii or other probiotics while they’re doing the protocol and after the protocol.  Then ironically, prebiotics often are a big part of the healing process.  This is where it gets tricky, because prebiotics are the fiber that feed the bacteria, which then produce hydrogen, which feed the archaea.  You have to make sure you reduce the levels of those bacteria and archaea first, and then come in with the prebiotics to rebuild a healthy gut flora that will make it less likely that you’ll develop this problem again in the future.  So it’s a pretty involved process, there’s a lot to it, and it has to be timed right.  But it’s definitely possible, and it works.  It just takes more time, in some cases, than people expect.  Generally, with SIBO, and especially if it’s a recalcitrant case and the levels of methane are really high, I tend to tell patients that this is going to be a 6- to 12-month process to fully deal with it, and that’s what we’re seeing in the clinic. Jordan Reasoner:  Well, Chris, I think we answered Simas’s question pretty in-depth today. Chris Kresser:  All right.  Great question.  Keep them coming, everyone.  It’s really fun to hear your questions.  Of course, we don’t have the chance to answer them all.  We try to choose ones that we think will be of greatest interest to the greatest number of people, and kind of spread out the topics.  Keep them coming and we’ll see you next week. Jordan Reasoner:  If you want to get more info about what Chris is researching in-between all these show recordings and all the studies that he’s sharing, head over to Facebook.com/ChrisKresserLAc and Twitter.com/ChrisKresser.  Thanks, everyone.

This is a guest post by Laura Schoenfeld, a Registered Dietitian with a Master’s degree in Public Health, and staff nutritionist for ChrisKresser.com. You can learn more about Laura by checking out her popular blog or visiting her on Facebook. And if you need one-on-one help with your diet, click here to learn more about her nutrition consulting services. Recently, I wrote an article about the potential pitfalls of following an excessively low carb diet, and the symptoms to watch out for to know if you’d benefit from adding carbs back into your diet. While I repeatedly pointed out that there are many people who thrive on a very low carb or ketogenic approach, there were commenters who staunchly disagreed with my recommendations. While I stand by my original article (as well as Chris’s subsequent supporting articles here and here), I wanted to make sure that those who would benefit from a very low carbohydrate or ketogenic diet were aware of the positive impact this nutritional approach can have when implemented correctly. Yes, you read that correctly: there are many people who can do incredibly well on a properly designed, nutritionally adequate ketogenic diet.

Some people find that they thrive on a very low carb or ketogenic diet. Could you be one of them?

In this article, I’ll describe seven different classes of people who could experience improved health and wellbeing by following a ketogenic diet, as well as briefly explain the precautions you’ll need to take if choosing to experiment with this therapeutic diet strategy.

Overweight and Obesity

One of the biggest draws of a low carbohydrate diet is that it can be a highly effective tool for rapid weight loss, especially in those who are significantly overweight and/or obese. When compared to low fat diets, dozens of studies show that a very low carb approach can be help those who are overweight lose weight, maintain lean muscle mass, and improve many of the metabolic risk factors for diabetes and heart disease, including elevated triglycerides, low HDL, and chronically elevated blood sugar. There’s no denying that a low carb diet can be a highly effective obesity treatment. Most people believe low carb diets cause weight loss so rapidly by lowering circulating insulin, but another reason why low carb dieting may promote weight loss is because these diets frequently lead to a spontaneous reduction in overall food intake. Combining that with low insulin and high glucagon levels is generally a recipe for immediate weight loss, though this is not always sustainable for a variety of reasons. The longer a person stays on a low carb diet, the more they may start to find ways to make their diet more palatable, and thus increase their overall calorie intake. Also, as weight loss occurs, a person’s overall calorie expenditure will drop, meaning that the same amount of food that made them lose weight in the first place will eventually cause them to maintain their weight - the dreaded “plateau”. If you’re eating more calories than you’re expending, even on a low carb diet, you won’t lose weight. If you’re using low carb as a weight loss diet, this doesn’t give you license to eat high fat foods in unlimited quantities. Eat good quality protein, plenty of non-starchy vegetables, and enough fat to meet your daily needs without going overboard and you may find that a nutrient-dense low carb diet is the perfect strategy for sustainable weight loss and reversal of metabolic syndrome. And remember - obesity is a far different health situation than trying to “lose the last 10 pounds”, so many of the same weight loss principles that work well for people who are significantly overweight may not work so well for those trying to reach their ideal “look good naked” weight. Keep that in mind when considering how much weight you want to lose and whether or not it’s truly necessary for health purposes. Those who don’t really have much excess weight to lose may be more prone to the potential problems with a long term low-carb diet.

Blood Sugar Imbalances

Blood sugar control plays an important part in weight management as well as the prevention of chronic disease, including diabetes, heart disease, cancer, and possibly even Alzheimer’s disease, among others. If your blood sugar is always elevated, you’re at an exponentially higher risk for dozens of diseases, and you’re more likely to die earlier from these diseases as well. So if you have consistently high blood sugar, you’ll likely find that reducing your carbohydrate intake significantly can bring that number down quickly, particularly if you’re relatively sedentary. Low carb diets can also be helpful in reactive hypoglycemia, a condition where blood sugar drops too low following a meal, causing symptoms such as dizziness, anxiety, shakiness, hunger, and confusion. This issue can be made worse by caffeine and stress, and I find it more commonly in my clients with adrenal issues. A common cause of this reaction is when a meal too high in easily absorbed carbohydrates is consumed, and blood sugar rises rapidly, leading to a release of insulin. The insulin causes a subsequent drop in blood sugar, and this drop can sometimes go too low or happen too quickly, leading to the hypoglycemic symptoms. If you’re someone who eats a lot of sugar-laden foods, or generally is eating a high carb, low fat diet, you may be more prone to these blood sugar swings that can lead to hypoglycemia symptoms. In this case, a reduction in carbs and an increase in fat at meals will help keep your blood sugar levels steady, and get you off the blood sugar roller coaster. But if you’re already eating a very low carbohydrate diet, a bit of healthy carbs at each meal may actually help normalize your blood sugar too, so it’s important to consider your current dietary habits before dropping your carbs any lower. And if you’re completely unsure where you stand on this issue, it might be worthwhile getting some help with your diet!

Neurological Disorders

One of the oldest uses of a ketogenic diet has been the treatment of seizure disorders  - even the Bible refers to fasting as a treatment for “fits”, and the ketogenic diet has been used by doctors as a treatment for epilepsy since the early 1900s. Though the creation of anti-seizure medication significantly reduced the reliance on this treatment, there has been a surge in the demand for this therapeutic diet over the past 20 years. These days, there are even dietitians who specialize in the ketogenic diet who work with patients, mostly children, suffering from frequent seizures. Other neurological conditions that have been shown to respond well to a ketogenic diet are Parkinson’s disease, Alzheimer’s disease, ALS, stroke, and dementia. (1, 2, 3, 4, 5, 6) In fact, Alzheimer’s disease is now being referred to as Type 3 Diabetes, highlighting the importance of blood sugar control in managing this often devastating condition. Ketogenic diets may also be therapeutic in the treatment of traumatic brain injury, a major cause of mortality and morbidity in young adults. (6a) One of the most comprehensive books covering the role of a low carb and/or ketogenic diet in the treatment of neurological conditions is Grain Brain by Dr. David Perlmutter, a well known neurologist. Dr. Perlmutter has had a great deal of success using low carb, grain-free, and ketogenic diets in the treatment of thousands of patients with neurological disorders. However, it’s important to remember that while these very low carb diets are helpful in treating these conditions, it’s unknown whether or not these restrictive diets would be necessary to prevent these conditions. Ultimately, I’d personally reserve the use of a ketogenic diet as a treatment for neurological disorders rather than a long term preventative diet.

Mood Disturbances

Similar to the neurological conditions already discussed, low carb and/or ketogenic diets may be helpful in reducing or eliminating symptoms of mood disorders like anxiety or depression. Some preliminary evidence suggests that these diets can have similar effects as antidepressant drugs. (7) Most of the research has been conducted in animals, but there have been studies showing benefits in improving aggression, fear behavior, and overall mood and quality of life. (8, 9, 10, 11) On the contrary, one study demonstrated a decline in overall mood in subjects on a low carb diet, energy-restricted diet compared to a low fat diet, while another showed a decline in mood in female cyclists following a low carb compared to moderate and high carb diets. (12, 13) There hasn’t been a ton of research on this issue, so ultimately you’ll have to determine for yourself what the appropriate level of carb intake will be for your particular mood issues. I’ve seen plenty of clients (myself included) who find that their levels of anxiety skyrocket on an excessively low carb diet, so what works for one person (or a rat!) may not work for you. Whether or not carbs are at play in your anxiety or depression, there’s a major role for a healthy diet and ancestrally appropriate lifestyle. I do believe food is medicine when it comes to mood issues, and I’ve seen multiple clients get off their antidepressants after making targeted, individualized changes to their diets, even if they were already eating “Paleo”. And none of these improvements required strict carbohydrate restriction, so a moderate intake on a nutrient-dense diet may be enough to see positive changes.

Polycystic Ovarian Syndrome (PCOS)

PCOS is an incredibly common endocrine issue in young women, with a prevalence as high as 15%-20% of women. Typically, PCOS affects ovulation and menstrual function in women, and can also cause an androgen excess. These changes are the root cause of many of the most frustrating symptoms, including amenorrhea, acne, hirsutism (male-pattern body hair), weight gain, dandruff, thinning hair, and mood issues. One of the primary dietary recommendations for women with PCOS is to limit refined carbohydrates and sugars, and to generally follow a lower carb diet. (14, 15) Reduced carbohydrate diets can help improve body composition, increase fat loss, repair insulin sensitivity, and promote menstrual regularity in these women (16, 17, 18) One pilot study found that overweight women following a low-carbohydrate ketogenic diet lost weight, reduced their testosterone levels, and decreased their fasting insulin. (19) These women also experienced non-significant decreases in insulin, glucose, testosterone, HgbA1c, triglyceride, and perceived body hair. Two women even became pregnant during the study, when they had previously been experiencing infertility. But before those of you with PCOS jump straight on a ketogenic diet, it’s crucial to note that there was no control group in this study. So it’s hard to know if the ketogenic diet was really necessary to get these results, or if a significant reduction in sugar, processed carbs, and grains might have been adequate, while still allowing these women to get a substantial amount of carbs from Paleo-friendly fruit and starchy vegetables. You may find that the right diet for you allows for plenty of healthy variety, and that a reduced carbohydrate, whole foods diet is enough to get you on the right path towards healing from your PCOS.

Small Intestine Bacterial Overgrowth (SIBO) and Reflux (GERD)

SIBO and GERD seem to be increasingly common these days, likely stemming from our overuse of antibiotics, inadequate exposure to healthy bacteria, poor dietary choices, and high levels of stress. In my work with clients, I’ve also noticed an uncanny connection between SIBO or reflux and a history of binge eating or bulimia disorder, so I’d guess that overeating in general can put someone at higher risk for low stomach acid and an overgrowth of bacteria in their small intestine. You can get great information about reflux from Chris’s free eBook on the topic. And if you’ve never heard of SIBO and you don’t know what the primary treatment for this condition is, I’d suggest listening to this podcast that Kelsey Marksteiner and I recorded for a great primer on the subject. But I’m sure some of you reading this either know what SIBO is, or actually have SIBO yourself. SIBO and reflux are often found simultaneously, so that’s why I’m lumping these two conditions together. One of the primary dietary treatments for SIBO and reflux is the restriction of fermentable carbohydrates, often referred to as FODMAPs. But some practitioners even recommend using a completely low carbohdyrate or ketogenic diet, as some bacteria can feed off of low FODMAP carbs and starches. It may depend on the severity of your SIBO case, and some SIBO patients do just fine restricting FODMAPs and simple sugars. And if you’re eating too many high FODMAP veggies on a low-carb diet, you may actually make the problem worse! Generally for reflux and/or SIBO, I tend to recommend a lower carbohydrate diet which restricts fermentable carbohydrates and sugar, but allows for a moderate amount of starches such as white rice or potatoes, which are often well tolerated. So while a strict low carb or ketogenic diet may be useful in dealing with these digestive disorders, I don’t think that it’s necessary to stay on these diets indefinitely to get the results you’re looking for.

Cancer...?

At the risk of opening a giant can of worms, I’ll briefly mention that there are many scientists, doctors and clinicians who promote the use of a low carb ketogenic diet for cancer. The major argument is that unlike the majority of our body cells, cancer cells lack the ability to metabolize ketones, and require a significant amount of glucose to survive and replicate. Since a ketogenic diet can keep blood sugar low, the theory (in a nutshell) is that cancer cells won’t be able to survive and thus the cancer will not grow and metastasize. Some doctors have reported amazing results in the use of these diets in helping their patients go into remission. There are a few studies that show potential benefits for some (but not all) cancer patients, especially brain cancer. (20, 21, 22, 23, 24) But another study showed that in 16 patients with advanced metastatic cancer, only 5 of the 16 patients recruited could even stick to the diet, and none showed any remission of the cancer, so it likely depends on the type and severity of the cancer whether or not a ketogenic diet will make any difference to the outcome. (25) And none of these studies show any data that suggests a ketogenic diet would be necessary or helpful to prevent cancer. When it comes to dietary recommendations and carbohydrate restriction for cancer patients, I don’t know if there’s enough data on the subject to make a strong recommendation either way. Ultimately, we’ll always have some level of sugar circulating in our bloodstream, and while I agree that good blood sugar control is likely helpful in preventing cancer in the first place, I’m not entirely convinced that a ketogenic diet is the best diet in all cancer patients, especially for those who are in more advanced stages. And having had relatives die from advanced stage cancer, I can also understand the fear that would come from feeding a cachexic cancer patient a hypocaloric ketogenic diet if they’re already wasting away. For now, I’ll “plead the fifth” on this topic, and wait and see if more studies come out in the future supporting this particular therapeutic use of the ketogenic diet.

Important Considerations When Starting A Low Carb Diet

As you can see, a low carb diet can be a good choice for certain people, as long as they pay attention to several important factors that can ensure their nutritional status isn’t negatively impacted by this somewhat restrictive diet. The biggest issue I see with many people who first switch to a low carb diet is that they’re unintentionally undereating, largely due to their discomfort with eating enough fat to make up for the carbs they’re not consuming. While this can be okay in the short term, especially for weight loss, over time this can lead to malnutrition and unhealthy stress on various organs, and may even cause weight gain as the body tries to conserve energy. If you’re on a low carb diet, make sure you’re eating enough to support your daily activity and to get a wide range of nutrients. Also, even though some of your favorite foods might be low carb - like bacon, cheese, steak, and butter - make sure you’re still eating plenty of nonstarchy vegetables. These will help keep your gut bacteria healthy, as well as providing a variety of important minerals that can get deficient on a low carb diet. Potassium is a particular mineral that is prone to deficiency on a low carb diet, so eating a wide variety of vegetables and low carb plant foods at every meal (in addition to nutrient-dense animal foods) will help keep you nourished. Avoid low carb products sold in the grocery store. These products often have artificial sweeteners and other additives that make them taste similar to their high carb counterparts, and sometimes can cause digestive distress in larger quantities. If you’re going to do a low carb diet, make sure you’re still eating real food and not buying a ton of low carb packaged food to replace the junk food you used to eat. It’s important to keep an eye on your blood work as well, since not everyone experiences positive results on a low carb diet. Franziska Spritzler is a low carb dietitian who explained the adverse effects she experienced on a low carb ketogenic diet, with her LDL cholesterol and particle number shooting up to a potentially dangerous level. While this won’t happen to everyone, if it does happen to you it may be a sign that the diet isn’t a great choice for your long term health. Finally, pay close attention to how you look, feel, and perform while on a low carb diet. While you’ll need to give it some time to truly determine if the diet can support your activity, energy, and daily lifestyle, it’s hard to know who will thrive and who will crash and burn on a long term low carb diet. If you’re experiencing negative health effects like excess weight gain, sluggishness, mood issues, or poor athletic performance after trying the diet for several weeks, it may be a sign that you’d do better on a more moderate carb approach. Don’t let someone else’s experience with the diet dictate how you should expect to feel. You’ll be your own judge when it comes to figuring out the most appropriate diet for you. And if you need help figuring out how to optimize your carbohydrate intake, don’t hesitate to get in touch with me - I’ve worked with dozens of clients in this situation and can help you figure out if a low carb diet is right for you. You can sign up for a free 15 minute consult and we’ll discuss your nutrition and health concerns and determine if you’d benefit from professional and personalized guidance. Now I’d like to hear from you - what side of the carbohydrate “fence” are you on? Low carb? Moderate carb? High carb? How did you figure out the right diet for you? Share your story in the comments below! About Laura: Laura uses her knowledge of traditional and biologically appropriate diets to improve her clients’ health. Growing up with a family that practices Weston A. Price principles of nutrition, she understands the foods and cooking practices that make up a nutrient dense diet. With her strong educational background in biochemistry, clinical nutrition, and research translation, she blends current scientific evidence with traditional food practices to help her clients determine their ideal diet. You can find her at AncestralizeMe.com, on Facebook, and Twitter!

This is a guest post written by staff clinician Amy Nett, MD.

The normal small bowel, which connects the stomach to the large bowel, is approximately 20 feet long. Bacteria are normally present throughout the entire gastrointestinal tract, but in varied amounts. Relatively few bacteria normally live in the small bowel (less than 10,000 bacteria per milliliter of fluid) when compared with the large bowel, or colon (at least 1,000,000,000 bacteria per milliliter of fluid). And, the types of bacteria normally present in the small bowel are different from those in the colon.

Why you should thank your small bowel and the beneficial bacteria that live there

The small bowel plays an important role in digesting food and absorbing nutrients. It is also an important part of the immune system, containing an impressive network of lymphoid cells (cells of the immune system that help fight infections and regulate the immune system).

Are you at risk for small intestinal bacterial overgrowth? Find out what the most common risk factors and symptoms are.

The normal (beneficial) bacteria that are an essential part of the healthy small bowel also perform important functions. These beneficial microorganisms help protect against bad (i.e. pathogenic) bacteria and yeast that are ingested. They help the body absorb nutrients, and also produce several nutrients (such as short chain fatty acids) and vitamins like folate and vitamin K. These bacteria help maintain the normal muscular activity of the small bowel, which creates waves that move the intestinal contents, like food, through the gut.    

What is SIBO?

SIBO, small intestinal bacterial overgrowth, is defined as an increase in the number of bacteria, and/or changes in the types of bacteria present in the small bowel. In most patients, SIBO is not caused by a single type of bacteria, but is an overgrowth of the various types of bacteria that should normally be found in the colon (1). Less commonly, SIBO results from an increase in the otherwise normal bacteria of the small bowel. 

SIBO has been shown to negatively affect both the structure and function of the small bowel. It may significantly interfere with digestion of food and absorption of nutrients, primarily by damaging the cells lining the small bowel (the mucosa). Additionally, this damage to the small bowel mucosa can lead to leaky gut (when the intestinal barrier becomes permeable, allowing large protein molecules to escape into the bloodstream), which is known to have a number of potential complications including immune reactions that cause food allergies or sensitivities, generalized inflammation, and autoimmune diseases (2).

These pathogenic bacteria, whether too many or the wrong types, can lead to nutritional deficiencies on top of those due to poor digestion or absorption. In particular, the bacteria will take up certain B vitamins, such as vitamin B12, before our own cells have a chance to absorb these important nutrients. They may also consume some of the amino acids, or protein, that we’ve ingested, which can lead to both mild protein deficiency and an increase in ammonia production by certain bacteria. (We normally produce some ammonia daily from normal metabolism, but ammonia requires detoxification, so this may add to an already burdened detoxification system.) The bacteria may also decrease fat absorption through their effect on bile acids, leading to deficiencies in fat soluble vitamins like A and D.

What causes SIBO?

The body has several different ways of preventing SIBO. These include gastric acid secretion (maintaining an acidic environment), waves of bowel wall muscular activity, immunoglobulins in the intestinal fluid, and a valve that normally allows the flow of contents into the large bowel but prevents them from refluxing back into the small bowel. (This is called the ileocecal valve because it’s located between the ileum, or terminal end of the small intestine, and the cecum, a pouch forming the first part of the large bowel.)

The cause of SIBO is usually complex, and likely affects more than one of the protective mechanisms listed above.  A number of risk factors for SIBO have been identified, with some of the more common risk factors listed below.  For a more complete discussion of associated diseases and risk factors check out this study and this study.

Risk factors for SIBO

• Low stomach acid
• Irritable bowel syndrome
• Celiac disease (long-standing)
• Crohn’s disease
• Prior bowel surgery
• Diabetes mellitus (type I and type II)
• Multiple courses of antibiotics
• Organ system dysfunction, such as liver cirrhosis, chronic pancreatitis, or renal failure

Moderate alcohol consumption and oral contraceptive pills (OCPs) also increase the risk for SIBO

Heavy alcohol use has long been recognized in association with SIBO (3). This study also found an association between SIBO and moderate alcohol consumption, defined as up to one drink per day for women and two drinks per day for men. Alcohol appears to have effects on several of the normal protective mechanisms, including causing injury to the small bowel mucosal cells, contributing to leaky gut, and decreasing the muscular contractions. Additionally, alcohol may “feed” a few specific types of bacteria contributing to overgrowth (4).

Overall there appears to be a moderate association between OCPs and inflammatory bowel disease (IBD) such as Crohn’s disease (5). Though no studies to date specifically correlate the use of OCPs with SIBO, given the known relationship between IBD and SIBO, it is likely that this association holds true for SIBO as well. However, once patients stop taking OCPs, this risk appears to reverse.

How do you know if you have SIBO?

The number of people with SIBO in the general population remains unknown. Some studies suggest that between 6 to 15% of healthy, asymptomatic people have SIBO, while up to 80% of people with irritable bowel syndrome (IBS) have SIBO (6). 

SIBO is largely under-diagnosed. This is because many people don’t seek medical care for their SIBO symptoms, and because many doctors aren’t aware of how common SIBO is. Complicating this, the most commonly used tests (breath tests measuring levels of hydrogen and methane gas) still have fairly high rates of false negatives (meaning the test results come back as negative but you actually do have the disease) (7).

The most common symptoms of SIBO include:

• Abdominal pain/discomfort
• Bloating and abdominal distention
• Diarrhea
• Constipation (generally associated with methanogens as Chris discussed in his recent podcast)
• Gas and belching
• In more severe cases, there may be weight loss and symptoms related to vitamin deficiencies.

Is SIBO contagious?

Unlike many other bacterial infections of the gastrointestinal tract, SIBO is not contagious, and there is no evidence that exposure to any single microorganism increases the risk for developing SIBO. SIBO occurs due to a complex interplay of many different factors and is not passed on between individuals.

Why SIBO can be difficult to treat

Antibiotics are often used to treat SIBO. However, studies show that despite treatment with antibiotics, recurrence develops in almost half of all patients within one year. One study comparing treatment with rifaximin (the most commonly used antibiotic for SIBO) and botanical antimicrobials showed slightly better outcomes with the botanical protocol, but still with successful treatment in close to only half of all patients after one course of treatment.

These finding suggests that treatment of the overgrowth alone is not enough for most people. An additional piece of successful treatment must include addressing the underlying cause, or predisposing factor.

Though there are many identified associations between SIBO and other diseases as described above, abnormalities in gut motility are recognized as one of the most common associations. One study published this month demonstrated that patients with SIBO do have significant delays in small bowel transit time (the amount of time it takes something to move through the small bowel). This finding suggests that patients with SIBO, who do not recover after a standard course of antibiotics, or botanical antimicrobial protocol (which we prefer), may benefit from the addition of a prokinetic agent, which increases the muscular contractions of the small bowel. Octreotide and low dose naltrexone are two such options that are being investigated, and may help treat some cases of SIBO that don’t respond to antimicrobials alone.

As research into SIBO continues, we are increasingly understanding the complexity of this disease, and how treatment must be tailored to each individual to maximize success.

Now we’d like to hear from you. Have you had SIBO requiring more than one round of antimicrobial therapy? What helped you recover from SIBO?

About Amy:  Amy Nett, MD, graduated from Georgetown University School of Medicine in 2007.  She subsequently completed a year of internal medicine training at Santa Barbara Cottage Hospital, followed by five years of specialty training in radiology at Stanford University Hospital, with additional subspecialty training in pediatric radiology.

Along the course of her medical training and working through her own personal health issues, she found her passion for functional medicine, and began training with Chris in June of 2014.  She has recently joined his clinical practice to work with patients through a functional medicine approach, working to identify and treat the root causes of illness.  Similar to Chris, she uses nutritional therapy, herbal medicine, supplements, stress management, detoxification and lifestyle changes to restore proper function and improve health.

This is an important topic and something that’s fairly commonly experienced. There’s not a lot of great information out there in the conventional medical world on how to troubleshoot neuropathy if you’re experiencing it. In this episode, we cover: 2:28 Potential Causes of Neuropathy 5:44 Testing for B12 Deficiency 10:10 Four stages of B12 Deficiency 14:40 Five Potential Causes of B12 Deficiency 17:36 Treating B12 Deficiency  [powerpress] Chris Kresser:  Hey, everyone. It’s Chris here. Steve is away. Unfortunately, he had a death in the family and Jordan is not available. So you’re stuck just listening to me go on and on for this episode. We’ll keep it relatively short, since listening to a monologue is never as interesting as a conversation. But this is an important topic and I figured I would just go ahead and do it, because it’s something that’s fairly commonly experienced, and there’s not a lot of great information out there in the conventional medical world on how to troubleshoot this if you’re experiencing it. Let’s go ahead and listen to the question, and then we’ll get started. Matt:  Hi, Chris. My question is, what sort of dietary changes, lifestyle changes, and possible supplementation would you recommend for neuropathy? As neuropathy can be associated with diabetes, B12 deficiency, toxin exposure, among other things, what tweaks would you make to your approach of those conditions, if neuropathy is also an issue? Similarly, if one just has idiopathic neuropathy, what recommendations would you suggest? Thanks. Chris Kresser:  Again, great question. As is often the case, diagnosis is really key. In functional medicine, we always want to address the underlying cause of a problem. That’s what’s going to lead to the most effective and longest-lasting change and solution. That’s the difference with the conventional model, which is often oriented more around symptoms suppression and disease management, irrespective of the underlying cause. For example, if you have high blood pressure, you take a medication to lower it. If you have high cholesterol, you take a medication to lower it. There’s oftentimes very little investigation into what the underlying causes of those symptoms or conditions may be.

Potential causes of neuropathy

With neuropathy, there are a number of potential causes, too many to cover in detail here. We’re going to focus on the ones that I think are the most common and most likely for listeners to be experiencing. Just to give you an idea of the many different things that can lead to neuropathy: we’ve got B12 deficiency; diabetes; toxic exposure, heavy metals; mold toxicity or something called chronic inflammatory response syndrome (CIRS), which I’m going to be talking more about in the future; liver-kidney disease; infections like Lyme disease; obstructive sleep apnea can worsen neuropathy. Then you have some drugs that have neuropathy as a side effect. Cardiac drugs for arrhythmias, certain antibiotics and antivirals that are used to treat HIV, some blood pressure medications, psychiatric drugs that are used to treat bipolar disorders, and anti-seizure medications. To use a really simple example, if you’re taking one of these drugs and you have neuropathy, the simplest solution would be to talk to your doctor about finding another alternative treatment that’s not going to cause that kind of side effect. But for most people who are listening to this, I imagine that the cause of their neuropathy is something else. B12 deficiency is, in my experience, by far the most common, and definitely the most common in my patient population. Statistically speaking, in the US, probably diabetes is the most common cause of neuropathy, because diabetes is just epidemic at this point. Then things like toxic exposure, mold toxicity, liver-kidney disease, and infections are probably less common causes. Again, the most effective treatment here will depend on the cause. If blood sugar is the issue, diabetic neuropathy, then there is some evidence that a ketogenic diet may be helpful. There’s one account in the scientific literature of a complete reversal of diabetic neuropathy after two months of a ketogenic diet. The caveat is that the study was done in mice, not humans, so we can’t say for sure that that’s going to apply to humans. But we have enough research behind the effects of ketogenic diets in many other conditions with humans that I think it’s at least plausible. And of course, all of the other things that we’ve talked about on the show and on my website and in my book about managing blood sugar, making sure you’re eating enough protein, making sure you’re getting enough exercise, particularly high-intensity exercise and strength training, can be helpful for improving metabolic health.  You want to make sure you’re getting enough sleep. We have tons of research now that shows how poor sleep contributes to diabetes and obesity. You want to make sure you’re managing your stress, reducing your intake of all of the highly-processed and refined foods that contribute to obesity and diabetes, and really focusing on real nutrient-dense, whole foods. We have all those basics. On top of that, doing a ketogenic approach for a period of time might be helpful, as the study I mentioned suggests.

Testing for B12 deficiency

The next cause is B12 deficiency. We’re going to spend a little bit more time on this, because it’s much more poorly understood in general, even in the sort of functional, alternative medicine community I think. I’ve written a couple of articles on B12 deficiency that you should definitely check out, if you haven’t already. If you just Google “Chris Kresser B12,” they’ll pop right up at the top. I go into some detail about the prevalence of B12 deficiency in various populations: omnivores, vegans, vegetarians. We talked about some really important information, not very well-known information about testing and diagnosis of B12 deficiency, which I’m going to kind of review here. Then we talked a little bit about treatment. One of the most important things to understand about B12 deficiency is that the serum B12 is not a very reliable marker for diagnosing B12 deficiency. When you measure B12 in the serum, you’re measuring all of the different cobalamins. Cobalamins are all the different B12 compounds. That ranges from the most inactive forms of cobalamin, like cyanocobalamin, to the more active forms of cobalamin, like methylcobalamin and adenosylcobalamin, which are referred to as active B12. That’s the type of B12 that can actually be delivered, get in the cells, and do what it’s supposed to do. Then there are intermediate forms of cobalamins, like hydroxocobalamin, which are not super active, but more active than something like cyanocobalamin. When you measure serum B12, you’re measuring all of those different B12s. So it would be possible to have a normal or even high level of serum B12, and have most of that be inactive, and still be suffering from B12 deficiency, because you don’t really have enough of the active B12 that gets in the cells. I’ve definitely seen that in my practice when I run B12 tests. Every patient that comes to my practice gets a blood test that includes B12. In many cases, we’ll also go on to do more advanced testing for B12 deficiency, which I’m about to tell you about. And I see many patients who have normal B12 levels in the serum, but have evidence of B12 deficiency using the more sensitive markers. So this is something that’s really important to understand. What are those sensitive markers? Well, the most practical and most available at this time is methylmalonic acid, or MMA for short. You can test methylmalonic acid in the urine or the serum. Methylmalonic acid is an organic acid. It’s a by-product of normal cellular metabolism. It’s converted into succinic acid via a B12-dependent enzyme. That enzyme only can use active B12. So if methylmalonic acid (MMA) is elevated, it suggests there’s not enough active B12 to make that conversion. Therefore, it’s a sensitive indicator for active B12 deficiency. Urine methylmalonic acid is thought to be more sensitive than serum methylmalonic acid as a marker, because MMA is more concentrated in the urine than it is in the serum. But there are a couple of caveats. Urine methylmalonic acid is not accurate in the case of kidney disease. So if you have kidney issues, it’s not a good marker for B12 deficiency. And serum methylmalonic acid is not accurate in cases of intestinal bacterial overgrowth, which we know is very common. In my patient population, intestinal bacterial overgrowth is far, far more common than kidney disease. In fact, in all the years that I’ve been doing this, I think I’ve only had a few patients with full-blown kidney disease. So I run urine methylmalonic acid as a result, because it’s much more reliable in my patient population. There is another marker that’s even more sensitive for detecting B12 deficiency. That’s called holotranscobalamin (holoTC). HoloTC is composed of B12 attached to transcobalamin. This represents the biologically active part of B12 that can be delivered into the cells.

Four stages of B12 deficiency

There are actually four stages of B12 deficiency. I want to go over them with you, because it really highlights the importance of using this more sensitive testing and the limitations of using serum B12, and then also markers like hemoglobin and red blood cells—the markers of anemia—to detect B12 deficiency. Stage I and II of B12 deficiency is when the plasma and cell stores of B12 become depleted, and transcobalamin is reduced. That’s all that happens in stage I and II. Typically, there are no other noticeable signs or symptoms. That is what holotranscobalamin (holoTC) will pick up. So there’s no other way that we know of right now to detect B12 deficiency in stage I and II, other than holotranscobalamin. Stage III characterizes functional B12 imbalance, which involves elevated homocysteine and blood methylmalonic acid. That’s where you can detect B12 deficiency using methylmalonic acid as a marker, in that stage III. That may manifest in some symptoms, but it’s often not obvious to either the patient or the doctor, that those symptoms are B12-related. I mentioned homocysteine. This is another marker that can be used to detect B12 deficiency at an earlier stage than serum B12. Homocysteine requires B12 and folate to be converted back into methionine. So if you see elevated homocysteine, you can suspect either B12 or folate deficiency. It’s important to understand that homocysteine is not specific to B12. The elevated homocysteine could be more related to folate deficiency than B12, so you can’t use it as an exclusive marker for B12 deficiency. But used in combination with methylmalonic acid, it can be really helpful for detecting B12 deficiency at that earlier stage. Stage IV of B12 deficiency is when the clinical signs and symptoms of it become evident. That’s when you start to see things like neuropathy, anemia, severe fatigue, and other symptoms that develop with B12 deficiency. If you think about this, in the conventional model, most people won’t even end up at the doctor until stage III or IV, because that’s when the symptoms start to become evident. By then, B12 deficiency has already progressed to the later stages. If it’s stage III, the doctor runs a serum B12 test, it’s in the normal range, they’ll say, “Oh, this isn’t a problem. Nothing to worry about.” But if you run homocysteine or methylmalonic acid in that stage, you’ll actually be able to detect it before it progresses into that stage IV, where in some cases, the effects of B12 deficiency, neurological damage, can be irreversible. So it’s really, really important to intervene at an early point here. So why not test holoTC, since it can detect stage I and stage II B12 deficiency? I would love to be able to test that. Unfortunately, it’s not a readily available marker right now. When I wrote the article that I mentioned earlier, Quest Diagnostics had listed it on their website. It’s listed as a test that’s available. But at least here in the Bay Area, it’s not yet available at any Quest lab location. I have yet to hear anyone that’s been able to reliably order it. Hopefully, that will change in the near future. For now, we can use methylmalonic acid and homocysteine to at least detect B12 deficiency that’s progressed to stage III. Fortunately, if you intervene at that point, it’s usually, in my experience, the symptoms of B12 deficiency, including neuropathy, are reversible at that point.

Potential causes of B12 deficiency

Let’s talk a little bit about what the potential causes of B12 deficiency are, because it is, as I mentioned, at least in my patient population, the most common cause of neuropathy. One would be pernicious anemia. This is often missed, I find. I’ve diagnosed several patients with pernicious anemia that didn’t know that they had it. This is an autoimmune disease that involves destruction of the parietal cells in the stomach. The parietal cells are where intrinsic factor is produced. Intrinsic factor binds to B12. The complex of intrinsic factor in B12 is absorbed in the small intestine. If you can’t produce intrinsic factor because your parietal cells are being attacked by your immune system, then essentially, you can’t absorb B12 orally. So people could be eating meat and all kinds of B12-rich foods like liver and shellfish, and they can still be B12 deficient. That’s important to understand, because it’s definitely true that B12 deficiency is way more common in vegans and vegetarians. According to recent tests that have used these more sensitive markers like methylmalonic acid, about 83% of vegans are deficient in B12 and 68% of vegetarians are deficient in B12, versus 5% of omnivores. But an omnivore who has pernicious anemia, for example, could still have B12 deficiency. Small intestinal bacterial overgrowth (SIBO) and low stomach acid can both impair the absorption of B vitamins, including B12. So I see B12 deficiency in people with SIBO. Glutathione deficiency can lower B12 levels, because one of glutathione’s roles is to protect B12 in the circulation. If it can’t protect it, then B12 gets damaged, and it can’t activate the cells as it should. So you could be glutathione-deficient if you have any kind of autoimmune disease, if you’re suffering from oxidative stress, if you’re not sleeping enough, if you’re not getting enough exercise or getting too much. Basically, anything that causes oxidative stress can deplete glutathione levels. Then impaired methylation can cause B12 deficiency or interfere with B12 metabolism. We talked a lot about methylation on a recent episode, so I’ll just refer you to that. Of course, inadequate dietary intake can cause B12 deficiency, which is why vegans and vegetarians have such high levels of B12 deficiency. There are really no adequate sources of B12 in the vegan and vegetarian diet. So if they’re not supplementing with B12 and preferably active forms of B12, then they could definitely have this problem.

Addressing B12 deficiency

In terms of addressing this, if it is B12 deficiency and it is dietary intake, of course, adding animal foods that contain B12 to your diet is a good idea, if you’re open to that. I list what the highest sources of B12 are in the articles that I mentioned, so check that out. Shellfish, organ meats, and meats, red meat in general, are among the higher sources of B12. If you’re going to supplement with B12, it’s best to take an active form. So methylcobalamin and/or adenosylcobalamin, which is sometimes referred to as dibencozide, are the best forms of B12. If you’re dealing with pernicious anemia, SIBO, or low stomach acid, you’re going to have problems digesting capsules or tablets of B12. The best thing to do would be to use a sublingual form, so that the B12 gets absorbed that way and bypasses the digestive route. I think I carry a form of B12 in my store that I recommend, which is Jarrow Formulas sublingual lozenge of methylcobalamin. There are studies that show that higher dose sublingual administration of B12 is as effective as injections in some cases. But what I’ve seen is that while most patients do well with B12 lozenges, sublingual form, some actually do better with injections, and they’re not comparable. So if you’re really dealing with pretty serious neuropathy, you’ve got B12 deficiency and have had it for a while, you’ve tried the sublingual lozenges and they’re not working for you, you may want to talk to your doctor about injections. You can get the active forms of vitamin B12 in injection. The typical injection that a doctor will prescribe will be the inactive form, cyanocobalamin. But you can get methylcobalamin injections. Those will generally be more effective. There are some other supportive nutrients for B12 deficiency. Those include folate; trimethylglycine; vitamin B6, or the active form, which is pyridoxal-5-phosphate (P5P); and vitamin B2, or the active form, which is riboflavin 5’-phosphate (R5P). If you’re dealing with a lot of oxidative stress and glutathione deficiency, then the antioxidants like vitamin A, E, and C, CoQ10, glutathione itself, selenium, which is important for immune regulation and glutathione production, N-acetylcysteine (NAC), and alpha lipoic acid (ALA) can all be really helpful in putting the brakes on oxidative stress. I think we’ll stop there. I know that was a ton of information. I didn’t have Steve to interrupt me and help you to absorb everything. Hopefully, that helps those of you who are dealing with neuropathy, especially if it’s related to B12 deficiency. We’ll talk to you next week. Steve will be back. Keep sending us your questions. We continue to get some really great questions and SI want this show to be all about you and what you want to know, so keep the questions coming in. We’ll talk to you next week.

This is a guest post written by staff clinician Amy Nett, MD.

Meet your microbiome

If you commonly read this blog, or listen to Chris’s podcast, you have undoubtedly developed an appreciation for the trillions of microbial organisms that normally inhabit a healthy small and large intestine. Most of these microbes are bacteria that have co-evolved with humans, depending on us for their survival just as we depend on them for our health and well-being. For example, we provide nutrients for bacteria which then keep our immune system in check, digest certain carbohydrates that would be indigestible to us, and make vitamins and other important compounds that we would otherwise be unable to produce. This wonderful, symbiotic relationship is what makes up your microbiome. A (hopefully) harmonious collection of microorganisms in our guts that aid in so many of our body’s vital functions.

The microbiome changes with disease

Our microbiome can affect us in multiple, profound ways ranging from how we store fat (1, 2, 3) to whether we feel happy, anxious or depressed (4, 5, 6). When the normal gut microbial communities are disturbed, whether you've used antibiotics or are suffering from a bacterial infection, it can lead to dysbiosis or small intestinal bacterial overgrowth.

Antibiotics, C-sections, poor diet, and autoimmune disease; what’s the connection?

Dysbiosis is associated with a growing number of diseases such as Crohn’s disease (7), ulcerative colitis (8, 9), irritable bowel syndrome (10), and both type 1 and type 2 diabetes (11, 12). You'll find that the variety and balance of gut bacteria is often different in patients with chronic inflammatory conditions as compared with healthy individuals. Research now suggests that these diseases are not due to any single bacterium, but from changes to the entire microbiome. And since a large part of our immune system is found within the gut, several diseases resulting from dysbiosis are autoimmune diseases.

What is autoimmune disease?

Autoimmune disease can be thought of as a case of mistaken identity: the immune system targets normal proteins as if they were harmful foreign invaders and becomes overactive. Normally, the immune system responds to a specific pathogen, like a cold virus, and once that pathogen is cleared, the immune system can settle down to its normal state. In the case of autoimmune disease, the immune system often stays on high alert, resulting in chronic inflammation.

With more than 80 different types of autoimmune disease, this class of disease has been particularly difficult to understand: what exactly causes the immune system to attack otherwise normal healthy human cells?

The three legged stool of autoimmune disease.

Dr. Alessio Fasano, a world-renowned gastroenterologist, expert in autoimmune disease, and pioneer in understanding celiac disease, describes autoimmunity as a three-legged stool, meaning that three essential components must be present in order for someone to develop an autoimmune disease:

1. Genetic predisposition: certain genes make individuals more likely to develop certain diseases.
2. A trigger: specific antigen, or protein, that the immune system recognizes as a threat (real or not), that sets off the cascade of over-activation. In the case of celiac disease, the trigger is gluten. However, in the vast majority of autoimmune diseases the trigger remains unknown.
3. Intestinal permeability (also referred to as “leaky gut”): this increased permeability means that the normally tightly knit cells of the intestines are weakened and "leaky". This allows large compounds, such as proteins from food or bacteria, entry into our bloodstream. Leaky gut can occur due to any number of reasons such a food sensitivities, gut infections, or chronic stress.

Does the microbiome play a role in autoimmune disease?

Increasing attention is being paid to the importance of the microbiome in health and disease—even slight imbalances have far reaching consequences. It has become clear that the microbiome profoundly affects our immune system, and new research provides insights into how changes in the microbiome can act as the trigger in developing autoimmune disease.

A recent paper reviewed some of the most recent research that the health of our microbiome may be the key factor in whether or not we develop an autoimmune disease (13). Below are a few of the key points:

Two of the most significant autoimmune diseases in terms of global morbidity and mortality are Type 1 diabetes mellitus, and rheumatoid arthritis (RA).

Type 1 Diabetes Mellitus

Type 1 diabetes (T1D) is an autoimmune disease with antibodies that destroy the insulin-producing cells of the pancreas, leading to insulin deficiency and blood sugar irregularities. Most often patients are diagnosed in childhood or adolescence, and there is a known genetic association. However, in studies with twins (who share the same genes), only about 50% of twins both go on to develop the disease. This further supports the idea that the development of disease depends on more than genes alone. For instance, immigrants have a risk of developing T1D that is dependent on their place of residence, not their country of origin.

Studies looking at differences in the gut microbiome between people with T1D and healthy individuals have found the following differences:

• Children with T1D have a smaller amount of beneficial bacteria.
• Children with T1D have less stability and diversity of bacteria in their gut.
• There are significant differences in both bacterial composition and metabolic capabilities between those with T1D and without.
• After treatments to normalize blood sugar in T1D patients, there was also a return to microbial diversity in those individuals.

Overall, the research is convincing that T1D is associated with a disruption in the normal microbiome. At this time, no single organism is responsible for the onset of this disease. However, in genetically predisposed individuals a disruption of the normal microbial communities provides an environment in which the disease may develop.

Rheumatoid Arthritis

Rheumatoid arthritis affects about 1.5 million people in the United States, and up to 1% of adults worldwide. It is an autoimmune disease that affects many of the joints throughout the body, most commonly the joints of the wrists and hands.

As with T1D, there is a known genetic association.  However, studies with twins again prove that genes play even less of a role in the development of RA when compared with T1D. Research again supports a relationship between the microbiome and the development and progression of RA. Of particular interest is the role of the bacteria living in ones mouth.

Periodontal disease and RA

• Patients with newly diagnosed RA have higher rates of severe periodontitis and more tooth loss despite normal oral hygiene compared to healthy individuals.
• The severity of a patients periodontal disease can be correlated with the severity of their RA disease activity.
• Specific bacteria that live in the mouth have been shown in animal models to increase the severity of joint disease.
• Specific bacteria are present in both dental plaque of patients with RA, and in joint fluid.

Many other autoimmune diseases are being studied to look for related dysbiosis, providing increasing evidence that disruption of the microbiome is associated with the development of some autoimmune diseases. Though there is clear correlation between changes in the microbiome and autoimmune disease, causation is not yet clear. This means we cannot say if it is the dysbiosis that leads to autoimmune disease, or if dysbiosis is the result of an overactive and misdirected immune system.

One more reason to take care of your gut?

As if we didn’t already have enough reasons to take care of our gut and help our beneficial bacteria thrive, it may be that decreasing our risk of developing an autoimmune disease is one more important reason to be good to your microbiome.

Now I’d like to hear from you: Have you made changes in your diet or gut health that have affected your autoimmune disease? Do you notice flares or exacerbations of your autoimmune disease when you eat certain foods?

About Amy:  Amy Nett, MD, graduated from Georgetown University School of Medicine in 2007.  She subsequently completed a year of internal medicine training at Santa Barbara Cottage Hospital, followed by five years of specialty training in radiology at Stanford University Hospital, with additional subspecialty training in pediatric radiology.

Along the course of her medical training and working through her own personal health issues, she found her passion for functional medicine, and began training with Chris in June of 2014.  She has recently joined his clinical practice to work with patients through a functional medicine approach, working to identify and treat the root causes of illness.  Similar to Chris, she uses nutritional therapy, herbal medicine, supplements, stress management, detoxification and lifestyle changes to restore proper function and improve health.

“Test. Don’t guess.” One of the tenets of functional medicine is you have to address the underlying cause of a problem in order to get the best result long term. You can’t address the underlying cause if you don’t know what it is. If you just assume that it’s yeast overgrowth based on some symptoms, that’s not really adequate in terms of making a diagnosis because the symptoms of fungal overgrowth are extremely nonspecific. Find out what you’re dealing with because the treatments will differ.

In this episode, we cover:

2:06  What Chris ate for breakfast 5:20  Is it really yeast overgrowth? 10:28  Diet for treating yeast overgrowth 21:51  When to use antimicrobials 24:15  Restoring and rebuilding the gut

[powerpress] Steve Wright:  Good morning, good afternoon, and good evening. You are listening to the Revolution Health Radio show. I’m your host, Steve Wright, co-author at SCDlifestyle.com. Revolution Health Radio is created for you and by you. It’s also brought to you by 14Four.me. 14Four.me is a 14-day healthy lifestyle reset program Chris has put together. Based on just working with hundreds of people and interacting with thousands of people on his blog, he has really realized, much like I have, that it’s just really hard to implement things that we talk about when it comes to healthy habits. Sleep, diet, exercise, and stress are all major components that we talk about on the show all the time. But to do them all at one time is pretty much guaranteed in the research literature, unless you have someone holding your hand, you’re going to fail. So 14Four.me does that in 14 days, where step by step, day by day, Chris actually walks you through how to do all of these healthy habits at the same time, so that you can do 14 days of really resetting, getting back to zero, and hopefully starting your new year off or whatever month it is right. If you haven’t checked it out yet, go over to 14Four.me and do that now. As always, with me is integrative medical practitioner, healthy skeptic, and New York Times bestselling author, Chris Kresser. Chris, how are you doing today? Chris Kresser:  Good, Steve. How are you? Steve Wright:  I’m pretty pumped, man. Chris Kresser:  All right. Steve Wright:  It’s a good day. Chris Kresser:  Good day. Yeah, it’s a beautiful day here as well. We have a good question. It’s one we get a lot and one that I think a lot of people are going to be interested in, and one that there are quite a few amiss and maybe misconceptions about.

What Chris ate for breakfast

Steve Wright:  Before we get into that though, Chris, we can’t go too many episodes without finding out what you were eating before the episode started. Chris Kresser:  Right. Not much to report today: coffee and cream (edit: usually I drink bone broth too). You know, we record the episodes a few weeks before they’re published, so this is actually right before Christmas. Lots going on. I’m getting on a plane soon to go visit family. There’s a lot happening. It’s a perfect opportunity to do some intermittent fasting. So that’s what I did today. Steve Wright:  Awesome. Yes, and that’s why my background is slightly different than the white walls. I’m at my parents’ house here in Michigan. Chris Kresser:  Nice. You don’t have the impressive phone cave that I have and that you normally have on. Steve Wright:  No, no. The audio quality is not going to be quite as well, but the background is a little bit more interesting. Chris Kresser:  Better scenery. Steve Wright:  Exactly. Chris Kresser:  Cool. Let’s give this question from Nada a listen. Nada:  I have a question for you about yeast overgrowth. I’ve been on the GAPS diet for about six months now. I’ve gotten better, but still having some symptoms, so I went to a holistic practitioner. She did the Metametrix test, the TRIAD test. It confirmed I had a yeast overgrowth. She wants me to start adding potatoes and things like that back into my diet, but I’m really scared to because I know that disaccharides are hard to digest. So I wanted to know what your recommendations are about yeast overgrowth, treating Candida, and sealing the gut barrier. Chris Kresser:  All right. Again, this is something that so many people are interested in. If you do some searching for Candida or yeast overgrowth on the Internet, you’re bound to just get bludgeoned with a crazy level of information. And a lot of it’s pretty kooky and quacky and unreliable. So I’m glad to have a chance to address this. I mean, we’ve talked about it here and there in the past, but it’s good to just do a really focused episode on it. Steve Wright:  Before you dive in, Chris, I just want to let everybody listening know that if you’d like to have your question answered, go to ChrisKresser.com/podcastquestion. Go there. Chris Kresser:  Hijack the show. Steve Wright:  Yeah, hijack the show. You want to talk to us? You have to go there. Chris Kresser:  Thanks for reminding me. It’s so great, as Steve said, to be able to make this show super relevant to you and your needs, and what you want to hear about. That’s really how it works. Definitely head over there and record a question. We want to hear your voice.

Is it really yeast overgrowth?

All right. I’m going to break this down into a few different categories. The first is not necessary based on what Nada said in her case. Or I’m assuming it’s a her. Sorry if it’s a he. But I want to point this out because it is something that often gets overlooked. It’s important for the general population that’s thinking about this. That is the question—is it really yeast overgrowth? One of my pet peeves is when I hear people say, “Oh, I’ve got yeast overgrowth,” or, “I’ve got Candida,” or, “I’m on a Candida diet.” I ask them, “How do you know that you have Candida?” And they say, “Well, because my tongue is white and I spit into a glass of water, and the saliva…” You know, all of these sorts of tests or even just symptoms that are not reliable as a means of diagnosing yeast overgrowth. There’s always an assumption made that it’s Candida, which may be, but it could be any number of other fungal species. It’s really important to test. I’ve always said on this show that we’re a big believer in the saying, “Test. Don’t guess.” Because one of the tenets of functional medicine is you have to address the underlying cause of a problem in order to get the best result long term. And you can’t address the underlying cause if you don’t know what it is. If you just assume that it’s yeast overgrowth based on some symptoms, that’s not really adequate in terms of making a diagnosis. That’s because the symptoms of fungal overgrowth are extremely nonspecific. What that means is there are things that could be caused by any number of other conditions that aren’t yeast overgrowth: fatigue, digestive discomfort, muscle aches, brain fog, low libido, hormone imbalance, skin rashes. These are all symptoms that could be attributed to Candida or fungal overgrowth, but they could also be caused by a parasite, SIBO, general dysbiosis. Or it could be something entirely different, like chronic infections such as Lyme disease, coinfection or a biotoxin-related illness, like a mold problem, exposure to a water-damaged building, or even potentially an autoimmune condition or a thyroid condition. And those are not all mutually exclusive. You can have fungal overgrowth and those conditions, and they often do go together. But the point is, you need to find out what you’re dealing with because the treatments will differ. I treat fungal overgrowth slightly differently than I treat SIBO, for example, or general dysbiosis or a parasite. Certainly, I would approach autoimmune disease differently than I would approach fungal overgrowth. There are pretty good tests for fungal overgrowth at this point. The best ones are stool tests through Genova (formerly Metametrix) or Doctor’s Data that can detect fungal overgrowth in the stool. You can get a urine organic acids test from Great Plains Laboratory. It’s a good one. Then the Genova Organix Profile is also a good one. They will detect organic acids, which are by-products of fungal metabolism in the urine. If they’re elevated, it’s a sign that there may be a fungal overgrowth. You can also test antibodies to Candida in the blood. So there’s a range of ways that you can get some objective data on whether you have Candida. In this case, as I mentioned, Nada already had the Metametrix test. I’m assuming she means stool, but she could mean the organic acids test as well, I’m not sure, and confirmed that there was a fungal overgrowth. It seems like she’s covered that base. Steve Wright:  Yeah. I think it’s really important, just to kind of reiterate what you were saying there, that a lot of the general symptoms or things that we notice in our lives when we’re sick could be attributed to yeast overgrowth, but they could be attributed to lots of other things. I don’t know what your experience has been, but my personal health history, as well as the people that I’ve worked with and the thousands I’ve talked to, typically, it’s not just yeast. Chris Kresser:  Yeah. Steve Wright:  So this idea of not testing and sort of just—or going off just one test and assuming, “Hey, I found something. That’s it. That’s the one singular root cause.” I think it’s really important to make sure people understand that that could set you back. That sort of belief could set you back quite a bit and have you wasting a lot of time and money. Chris Kresser:  Great point. I agree. I would say maybe 15% of the time or 20% max, it’s just fungal overgrowth without SIBO, parasites or some other issue. 80% or 85% of the time, it’s something else in addition to fungal overgrowth. Great point, Steve.

Diet for treating yeast overgrowth

Moving on to the second point, which is the appropriate diet for treating yeast overgrowth. Nada mentioned she’s been on GAPS for six months. This is certainly a good choice, with some caveats, for yeast overgrowth. Now, if you’re not familiar with GAPS, it’s based on a specific carbohydrate diet. Both of those approaches remove complex carbohydrates—polysaccharides and disaccharides—from the diet. So when we talk about carbohydrates, we’re talking about different arrangements of glucose molecules. We have monosaccharides, which are single sugars like glucose, which are very rapidly absorbed in the upper part of the small intestine. They just don’t require a lot of absorption, because single molecules can pass directly across the lumen of the gut into the bloodstream. Then you have things like disaccharides, which would be lactose, as an example, which have to be split. They’re double sugar molecules. They have to be split into single sugar molecules before they can be absorbed. In people with poor digestion and absorption, fungal overgrowth, SIBO, and these conditions, those disaccharides don’t get properly broken down. They linger around in the gut, and they can become food for pathogenic yeast, bacteria, and other critters in the gut that we don’t necessarily want to be feeding. Then polysaccharides would be starches or any carbohydrates that have longer chains of glucose molecules linked together. They’re even more difficult to break down. That’s the theory with Gut and Psychology Syndrome (GAPS) and Specific Carbohydrate Diet (SCD). So the idea is if you have a fungal overgrowth, you should avoid disaccharides and polysaccharides, because they’re difficult to break down and they may potentially feed these overgrowths or infections. Now I want to point out that overgrowth is probably the best term, because Candida is a normal resident of the digestive tract, as are many other species of bacteria that become overgrown in SIBO. It’s not like you have an infection with a parasite or something that shouldn’t be in the gut but is there. What’s generally happening in these situations is if something that is normally in the gut has become overgrown and overrepresented in relation to some of the other beneficial species of gut bacteria. So the reason I mention that is because it hints at a different approach. The idea is not to just completely wipe out these species, because that’s not even necessarily desirable. The idea is to get things back into balance. That’s really the focus of any kind of treatment for fungal overgrowth. Steve Wright:  That’s such a great point, Chris, that I think has taken a long time to sort of begin to get out in the world. So a lot of the articles people are going to be reading when they have yeast overgrowth are not pointing that out. I think that’s one of those other fundamental beliefs, that if you have the belief that all yeast is bad or something like that, then you’re probably going to adopt a different treatment strategy that I think you and I have both seen to be very ineffective. Chris Kresser:  Yeah. Well, the systemic antifungal drugs are a good example of that. They can just really wipe out fungal species in the body. That can have a pretty dramatic effect. When you move from yeast overgrowth and you start using those drugs, you can have a big improvement in symptoms. But if you take them for too long, you start wiping out the beneficial yeast in the body. Beneficial yeast actually protect against bacterial overgrowth. So ironically, what happens with long-term use of those systemic antifungals is you can have a higher risk of SIBO, bacterial overgrowth, and dysbiosis that’s caused by a lack of beneficial yeast. You know, we need to get away from this warlike mentality that we have with—I mean, I think this came out of the whole age of antibiotics and the discovery that pathogens cause disease. That was an important discovery. But it led to this sort of warlike mentality where we’re going to use these powerful drugs to absolutely obliterate and destroy bacteria and other pathogens. But of course, now we have a much different understanding, where we know that these bacteria are—we live in symbiosis with them. We absolutely depend on them for not only our survival, but for several different aspects of health. So we’ve gotten a little bit overzealous in our killing mentality.  I think in the next—it’s already shifting, as you said, Steve. Within the next 10 to 20 years, there’s going to be much more of an appreciation of balance and regulation of the ecosystem, rather than the carpet bombing type of approach we’ve been doing so far. Back to the diet. The trouble with GAPS and SCD, depending on how they’re done, is that they can be extremely low-carb diets. If they’re extremely low-carb, they can become ketogenic, which means you start producing ketones. Paul Jaminet was one of the first people to start talking about this a few years ago. But there are several studies that suggest that Candida and other yeast can actually thrive on ketones. So this is one of my biggest problems with a very low-carbohydrate diet—GAPS, SCD or even sort of typical Candida diet—that removes every possible source of glucose or sugar in the diet. That can lead to ketone production. Then there are studies, for example, that show that neutrophils, which are white blood cells, are less able to kill Candida when ketones are present. There are studies of diabetic patients with ketoacidosis—you know, a lot of ketone production—developing Candida overgrowth. There are studies of obese people developing Candida infections when fasting causes ketosis. There are studies showing that serum drawn from fasting patients is less protected against Candida than serum drawn after meals, and that antifungal drugs, and I would assume botanicals, tend to work better in a fed state than a fasted state, where ketone production would be occurring. So there’s this whole kind of constellation of evidence that’s pointing to the idea that ketone production is not a good idea. I guess what I would say is if you do do a GAPS or especially like a GAPS intro or an SCD intro, that should probably be temporary. Even then, you might not want to do it so that it’s so low carb. You can test your urine with Ketostix to make sure that you’re not in ketosis and you can eat more of the non-disaccharides—you know, the safe fruits, for example, that are permitted on the GAPS or the SCD diet, if you’re continuing to avoid the disaccharides and polysaccharides, like the starches and the more complex sugar molecules. Steve Wright:  I think it’s important to sort of point out what I think you’re hinting at, which is that these diets—GAPS and SCD, which I’m a big fan of and have done a lot of work around—are not the solution. Chris Kresser:  Yeah. Steve Wright:  It’s another form of sort of starving and destroying. A lot of people, including myself, have gotten a lot of benefit from being on a diet like this. But the idea that any one of these diets is going to starve or kill yeast infection or a SIBO infection is, in my opinion, thoroughly false now. Chris Kresser:  You’re a step ahead of me. That’s point number three that we’re about to make. Steve Wright:  Okay, cool. Chris Kresser:  Awesome. We’re on the same page. Before I go on, I do want to say that generally, in my practice, I don’t start people with GAPS or SCD for fungal overgrowth or SIBO. We use a low-FODMAP diet for those conditions. I find that that typically works very well. FODMAPs are a slightly different take. It’s a similar theory. The idea is FODMAPs are fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. So there are certain types of carbohydrates that are poorly broken down. They become food for the fungal overgrowth or bacterial overgrowth. However, with a low-FODMAP diet, I think it’s easier. There are more carbohydrates that are permitted, including some starches, which might seem contradictory to the GAPS approach. And it is. It’s a different approach. But I found that many people can tolerate some starches on the FODMAP diet if they have fungal overgrowth and bacterial overgrowth. They do well and we see success. You know, we test people and then we retest people after they’re treated. We see the fungal markers and the bacterial markers changing and going away. If they don’t, we might then switch to like a GAPS or SCD intro, as long as there are enough carbohydrates so that it’s not ketogenic. I think either of those will work. Low-FODMAP diet is a starting place. GAPS or SCD, as long as you’re eating enough fruit and carbohydrates, so that you’re not going into ketosis. And again, you can test that with the Ketostix, which are these urine strips. Those are both good choices. Steve Wright:  One thing that neither one of us have mentioned—probably because we don’t like it or don’t like to mention it—is the anti-Candida diet, which anybody who’s Googling this issue is going to run into a thousand websites that talk about this. Chris Kresser:  Yeah. I’m right there with you. I was just about to mention that I’m not a big fan of the anti-Candida diet. I think it’s both unnecessarily restrictive and not restrictive enough. In the unnecessarily restrictive category, it removes literally every source of glucose. I mean, on the extreme versions, you see even carrots and things like that prohibited because they have too much sugar. However, as I mentioned, if you do that, you’re going to probably end up in ketosis, which can actually make things worse. And I’ve just never seen any peer-reviewed evidence that suggests that that’s necessary. In terms of the not restrictive enough, many Candida diets actually permit grains, which is strange when they’re trying to get rid of every source of sugar. Grains are ultimately carbohydrate, for the most part. They’re also poorly broken down for many people because they’re complex carbohydrates. So you’ll see the anti-Candida diet permitting grains, particularly the alternative grains like quinoa, millet, and things like that. I just don’t see those things working well for most people who have gut issues. That’s something to keep in mind. I don’t think the anti-Candida diet is very effective. If it was, you wouldn’t see people on it for years and years having the experience that they have. So that’s something to be avoided.

When to use antimicrobials

Point number three is what you just mentioned a little while back, Steve. That’s this—diet is not typically enough to treat fungal overgrowth and SIBO, in my opinion. It’s definitely a big part of strategy and it’s important. But when we have a patient that has fungal overgrowth or SIBO, we absolutely, without exception, will use antimicrobials. We start with botanicals. 90% of the time, that’s what we use. In some cases where the patient has just recurring, recalcitrant infections, we might start to use some prokinetics like low-dose naltrexone and possibly rifaximin and neomycin, if they have a methane overgrowth, which are medications. But almost exclusively, we’re using botanical, nutrient-based protocols. Some of the ones that we use, that have research behind them, and tend to work well would be undecylenic acid; uva ursi; cat’s claw; pau d’arco; lauric acid, which is monolaurin (Lauricidin); high-dose biotin actually is antifungal, like 5 mg per day; Gymnema sylvestre, which is an herb that has been used historically in India for blood sugar issues because it reduces sugar cravings and helps balance blood sugar, has recently been shown to be very effective in terms of inhibiting Candida growth; Saccharomyces boulardii, which is a beneficial strain of yeast, has been shown to inhibit the growth of Candida and also reduce inflammatory cytokine production that is associated with cells that are infected with Candida; soil-based probiotics like Prescript-Assist are I think effective in terms of outcompeting Candida for adhesion sites in the gut. So all of these things, many of which we’ve talked about before, can be really effective in an overall antifungal strategy. I think they’re very important. And if you’ve been doing a GAPS approach, for example, for six months, and you still have symptoms and you’re not doing these other things, then that’s absolutely something to look into.

Restoring and rebuilding the gut

The last point would be—remember the kind of two-phase approach, which is when there’s any kind of infection, the first phase is clearing out the infection and the pathogens or the overgrowth, if it’s not an infection but it’s an overgrowth. But the second phase is really important as well. That’s restoring and rebuilding. The reason you can’t necessarily do both at the same time is some of the things that you use to restore and rebuild, like prebiotics, for example, can actually make the overgrowth worse. So resistant starch and non-starch polysaccharides, which are FODMAPs, of course, and also prohibited on a GAPS type of approach, they’re really helpful over the long term for restoring, growing beneficial bacteria in the colon. The reason you want to do that is because that’s what’s going to prevent a recurrence of fungal overgrowth in the future. What I often see happening is patients will focus too much on the killing part and the eradication. They’ll stay on that diet or that approach kind of perpetually. They’re essentially continuing to starve their good gut bacteria. It’s interesting to see that there have even been studies about this now. I recently saw a paper that essentially was saying, something that we could have talked about, Steve, on the show. But the paper was saying, “Yeah, the low-FODMAP diet is undoubtedly effective for IBS, but maybe we don’t want to be prescribing this to patients long term because it’s really low on microbiota-accessible carbohydrates, which are the types of carbohydrates that feed the beneficial gut bacteria.” Now, of course, we know how important that is over the long term. I thought it was a great paper, because the researchers were basically backing up what we’ve said numerous times on this program, which is you have to distinguish between a therapy, something that has a therapeutic effect and that you use for a short period of time until you don’t need it anymore, with something that you might do over the long term. To use an analogy, if you need a raft to cross the river, when you get to the other side of the river, you just leave the raft behind. You don’t carry it on your head—well, unless you’re doing some portage and you’re expecting another river pretty soon. But the basic idea is you use it when you need it, and then you leave it behind. For whatever reason, people have a really hard time grasping that.  You see that in the low-carb world I think, where I think it can be a super effective therapy and a shorter-term approach for a lot of conditions and people, but doesn’t necessarily need to be the lifetime approach. Or the fact that it tends to work really well as a therapeutic intervention, that doesn’t necessarily translate into meaning that eating carbohydrates led to the condition in the first place. It all tends to get kind of convoluted. The point here that I really want to stress is that once you get the Candida or fungal overgrowth back into balance, that’s not the stopping place. The next step from there is to rebuild then your beneficial gut bacteria, which is what will prevent the Candida from getting overgrown again. I can tell you, and I’m sure you’ve had this experience, Steve, that people who get Candida, they don’t often just deal with it once; it tends to recur and be an issue. I think one of the reasons for that is they don’t stress the rebuilding part as much as they should. Steve Wright:  All right. So I’m just going to recap this. Correct me if I’m missing any here, Chris. But working backwards, one that you just mentioned was people tend to stay in the killing phase too long and don’t think about actually rebalancing the microflora and actually feeding it. Some people assume that diet is the solution to yeast and fungal overgrowth, when many times, it’s not; there needs to be other interventions. When people do do diets to try to help with yeast overgrowth and Candida, they typically will end up on a ketogenic diet, which can actually inhibit sort of the short-term treatments that will actually get rid of the Candida. Then I think another big one that we mentioned was the idea that—I think you put around 80% to 85% of the time, it’s not just a yeast overgrowth issue. I think this is one of the reasons why people keep getting yeast overgrowth as well. It’s because they don’t ever get off the killing protocol. They don’t realize that there’s an 80% chance or more that they have maybe another infection, they have a hormone issue or they have an autoimmune issue that they’re not looking at. Chris Kresser:  Yeah. Great recap, Steve. Perfect. Maybe we’ll call this episode, “Four Biggest Mistakes People Make When Treating Yeast Overgrowth.” Steve Wright:  Awesome. Chris Kresser:  I like it. All right, everybody. Thanks for listening again. Remember to submit your questions so your voice can be heard. Thanks, as always, for listening. Steve Wright:  In-between episodes, if you want to get Chris’s latest studies or the latest recipes he’s posting, things like that, make sure you’re following him on social media. If you’re a Facebook user, go to Facebook.com/ChrisKresserLAc. If you’re a Twitter user, go to Twitter.com/ChrisKresser. Thank you for listening. We’ll talk to you on the next show. Chris Kresser:  Thanks, everyone.

Choline is a crucial nutrient for gut, skin, neurological, and cellular health. Yet, according to the 2003-2004 National Health and Nutritional Examination Survey (NHANES), only 10 percent of Americans consistently meet the adequate intake for choline (1).

Choline also plays essential roles during growth and development, and the body’s need for choline increases during pregnancy. The amniotic fluid surrounding the baby in the womb is highly enriched with 14 times the level of choline found in the mother’s blood (2). Sadly, an estimate from 2014 indicates that 90 to 95 percent of women fail to meet recommended choline intakes during pregnancy (3).

Additionally, new research has identified human gut bacteria that can compete with the host for choline. This means that those with gut dysbiosis, and particularly those with small intestinal bacterial overgrowth (SIBO), could be at risk for choline deficiency, even if they are consuming choline-rich foods or taking choline supplements.

In this article, I’ll cover all of the relevant research surrounding choline for general health and pregnancy, including the role of our gut microbes, and discuss how we can use this information to optimize choline status.

The importance of choline

Choline carries out many important functions in the body. It is an essential component of phospholipids, which make up the structure of cell membranes. Choline is also a precursor to the neurotransmitter acetylcholine, which plays roles in memory, circadian rhythms, and muscle control, and sphingomyelin, which is found in the fatty sheath around nerve fibers and improves the conduction of electrical impulses. The transport of fat and cholesterol from the liver also requires choline, and deficiency can lead to non-alcoholic fatty liver disease (NAFLD) (4).

9 out of 10 Americans don’t get enough choline, and deficiency may be especially harmful during pregnancy. Certain gut microbes could prevent proper choline absorption. Learn how to optimize your choline status to support overall health. 

Choline is also an important source of methyl groups. The addition of methyl groups to the DNA structure can turn genes on or off without any changes to underlying DNA sequence, a process known as epigenetics. Epigenetics plays an important role in health throughout life but is particularly important during growth and development, as fetal stem cells divide and differentiate into organs with all kinds of complex cellular functions. Changes in DNA methylation have been associated with cancer, aging, cognitive disabilities, atherosclerosis, and autoimmunity (5).

In utero, choline status also has implications for the structural development of the hippocampus, the primary brain region responsible for learning and memory (6). Poor maternal choline status may also increase the risk of neural tube defects and impair development of the heart (7).

So how much choline do we need?

Unfortunately, there is still a lack of consensus on exactly how much choline we need. The Institute of Medicine, which establishes the RDAs for nutrients based on peer-reviewed studies, has been unable to come up with a definitive value for choline needs and has had to resort to establishing an “Adequate Intake” value for choline (8). This is sort of a “best guess” as to how much choline might be sufficient for most people.

Below are the adequate intake values for choline (9):

Infants (0–6 months old): 125 mg per day
Infants (6–12 months old): 150 mg per day
Children (1–2 years old): 200 mg per day
Children (4–8 years old): 250 mg per day
Children (9–13 years old): 375 mg per day
Adult men: 550 mg per day
Adult women: 425 mg per day
Pregnant women: 450 mg per day
Lactating women: 550 mg per day

Chris Masterjohn has previously explained why trying to estimate how much choline we need is almost impossible. He has also extensively discussed the factors that influence dietary choline requirements, including genetic variations, intake of other B vitamins (particularly other methyl donors), and overall energy intake. Thus, I won’t be discussing any of these factors here. Since the microbiome is my area of expertise and the newest identified factor affecting choline status, the rest of this article will focus on gut bacterial influences on choline requirements.

Microbes compete for host choline

A recent study from the lab of leading microbiome researcher Dr. Federico Rey suggests that our gut microbes may influence choline status (10). I find this fascinating, but if you get bogged down in the details, you can skip ahead to the end of this section, where I’ll discuss the implications of this research!

This study used what are known as gnotobiotic (know-toe-by-ah-tic) mice. These are mice colonized with a known community of microbes. In this case, the researchers chose a core community (CC) of five microbes that are abundant in the normal human gut. To half of the mice (CC+), they also added a strain of E. coli that is known to metabolize choline. To the other group (CC-), they added the same strain of E. coli, but mutated the enzyme responsible for choline metabolism. Thus, the only difference between the groups was that one could utilize choline, while the other could not.

The researchers then took blood samples and found that CC+ mice had very low levels of serum choline compared to CC- mice. This suggested that the E. coli microbe was competing with the host for choline.

Moreover, they found that CC+ mice had lower levels of DNA methylation that mimicked those seen in choline deficiency. To explore the implications of these altered methylation profiles, Dr. Rey and colleagues repeated the experiments in mouse models of metabolic syndrome and pregnancy and early life.

• In the metabolic disease model, CC+ mice had increased circulating leptin, increased blood triglycerides, and fatty livers compared to CC- mice.
• In pregnancy, mother CC+ mice had increased obsessive grooming behavior, and their offspring showed increased marble-burying behavior, indicative of increased anxiety.

So, what are the major takeaways? First, gut bacteria may impact choline bioavailability in ways that mimic outright choline deficiency. Therefore, we can’t just be concerned with the adequate intake for choline, as individual needs for dietary choline are dependent on the gut microbiome. This study also suggests that excessive bacterial metabolism of choline could be especially harmful in pregnant women and those with metabolic syndrome.

Could SIBO be causing choline deficiency?

Additionally, what most people didn’t catch in the methods of this study is that the choline-hungry E. coli strain used in the study is a robust colonizer of the small intestine.

To help convey the importance of this, I should review some basic gut anatomy. Food passes through the stomach to the small intestine, and then through the large intestine. It’s no mistake that the small intestine, the primary site of nutrient absorption, is upstream from the large intestine, which is home to the bulk of the gut microbiota. In a healthy individual, this arrangement ensures that our epithelial cells have “dibs” on any incoming nutrients, and our microbes get the “leftovers.”

In small intestinal bacterial overgrowth (SIBO), however, the pecking order changes. Microbes from the colon move up the gastrointestinal tract to colonize the small intestine, or small intestinal microbes flourish and become overgrown. These microbes now directly compete with the host for any incoming nutrients—and in many cases, they win out. SIBO may particularly affect host status for nutrients absorbed in the lower small intestine, such as iron, vitamin B12, and—based on this research—choline.

In other words, those with SIBO may be at particularly increased risk for choline deficiency. (This remains to be confirmed in humans, but the microbial strain used in this mouse study was isolated from the human gut.)

Could high circulating TMAO be linked to SIBO?

What is most intriguing is that choline bacterial metabolism also leads to high serum levels of TMAO (trimethylamine N-oxide). TMAO has received a great deal of attention for its associations with cardiovascular disease (11). Bacteria convert choline to TMA, which is then oxidized in the liver to TMAO. Chris has talked about TMAO before on both his blog and his podcast, suggesting that high serum TMAO levels are more about which gut microbes you have and less about how much choline and carnitine you consume. The study I outlined above provides support for this hypothesis: CC+ mice had much higher levels of TMAO, while CC- mice had virtually undetectable TMAO.

Additionally, preliminary data from the Rey lab has shown that in humans, low serum choline tends to be associated with high TMAO, and vice versa. If TMAO was primarily being produced from “leftover” choline in the colon, we likely would not see this relationship. This suggests that those with high TMAO are very likely harboring some form of SIBO—further explaining the connection between SIBO and cardiovascular disease. Indeed, a 2017 study confirmed that TMA is only absorbed in the small intestine. Moreover, an acute dose of rifaximin, the non-absorbable antibiotic most commonly used to treat SIBO, can reduce serum levels of TMAO (12)!

Could betaine help overcome choline deficiency?

In thinking about solutions to choline deficiency, it’s important to note that one of choline’s most important roles in physiology, that of a methyl donor, first requires the conversion of choline to betaine. In other words, it’s betaine that acts as the direct methyl donor. Betaine cannot completely fulfill choline requirements, since choline has several functions besides methylation, but it can help prevent some of the epigenetic consequences of choline deficiency.

While betaine can also be consumed by microbes (and lead to TMAO production), betaine is primarily absorbed high in the proximal (upper) small intestine, whereas choline is absorbed lower, primarily in the distal (lower) small intestine (13). Since SIBO is most common in the distal small intestine, this means that, theoretically, betaine may have a better chance to be absorbed than choline. Of course, this is all speculation, and I look forward to seeing more studies in this area.

Additionally, I’d muse that consuming both betaine and choline may increase the chances that at least one is absorbed, since different bacterial species compete for each of these two nutrients. Many people with SIBO supplement with betaine HCl to help correct low stomach acid—but betaine HCl may also help compensate for bacterial choline metabolism in the small intestine and prevent symptoms of choline deficiency.

How to optimize choline status

Putting all of this information together, there are several steps we can take to help optimize choline status (even if we don’t know exactly how much we need):

1. Treat SIBO and gut dysbiosis: As always, we want to treat the underlying cause of disease. In this case, if SIBO is contributing to choline deficiency, addressing SIBO may improve choline status. This involves taking antimicrobials, improving gut motility, and restoring adequate stomach acid levels. Klebsiella and Escherichia appear to be particularly thrifty choline consumers.
2. Consume plenty of choline-rich foods: the top whole-food sources of choline are listed below. Human breast milk is also rich in choline.
   • Beef liver (3 oz.): 356 milligrams
   • Eggs (1 whole): 147 milligrams
   • Beef round steak (3 oz.): 117 milligrams
3. Supplement with (phosphatidyl)choline: For those who cannot get sufficient choline from dietary sources, I recommend supplementation. It’s important to note that most prenatal supplements and multivitamins do not contain choline, and those that do often contain the choline chloride form.

I recently had the opportunity to ask Dr. Rey about his thoughts on various choline supplements. He suggested that while all forms of choline are used by microbes, phosphatidylcholine seems to take more work for the microbes to utilize and may have a better chance of being absorbed than compounds like choline chloride. This is also the form found naturally in most foods. I like Seeking Health Optimal PC.

While it’s possible that consuming extra choline may fuel the overgrowth of choline consumers, the consequences of inadequate choline are far too great to even consider restricting choline intake.

• Consume betaine-rich foods: as I discussed above, consuming adequate betaine may reduce the need for choline. The top three whole-food sources of betaine are:
• Beets (1 cup, raw): 175 mg
• Spinach (1 cup, cooked): 160 mg
• Sweet potato (1 medium): 39 mg
• Supplement with betaine: For those with SIBO and inadequate stomach acid secretion, betaine HCl is an excellent choice. I recommend one to five capsules, as tolerated, taken with meals.

I’d love to hear from you. What do you think of the research? Do you get enough choline and betaine? Share your thoughts in the comments!

About Lucy: Lucy is an MD-PhD student in Nutritional Sciences at the University of Illinois and a staff research associate for Kresser Institute. Her laboratory research focuses on the effects of diet and exercise on the gut microbiome and how this impacts gut and skin health. She was recently recognized as an emerging leader in Nutritional Sciences by the American Society for Nutrition and has contributed to several peer-reviewed publications.

Lucy’s mission is to provide evidence for an individualized, integrative approach to health through innovative research and outstanding clinical practice. She recognizes that each individual is unique, and she currently helps clients with gut, skin, and autoimmune conditions. You can learn more about her at NGmedicine.com or join her weekly newsletter here!

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