Episode 13 – Small Intestine Bacterial Overgrowth (SIBO) with Dr. Leonard Weinstock Link: https://tinyurl.com/tfcm9dty

00:00:01 Announcer: Welcome to the Standing Up to POTS podcast, otherwise known as the POTScast. This podcast is dedicated to educating and empowering the community about postural orthostatic tachycardia syndrome, commonly referred to as POTS. This invisible illness impacts millions and we are committed to explaining the basics, raising awareness, exploring the research, and empowering patients to not only survive, but thrive. This is the Standing Up to POTS podcast.

00:00:29 Jill (Standing Up to POTS): Hello fellow POTS patients and nice people who care about POTS patients. I'm Jill Brook and today we are going to discuss a particular GI issue that can be associated with POTS called SIBO, S-I-B-O, which is short for small intestinal bacterial overgrowth. Our guest is an amazing physician and researcher, Dr. Leonard Weinstock, who has made a big difference in the lives of many POTS patients like me with his very important research and clinical findings. He is board certified in both gastroenterology and internal medicine. He is president of specialists in gastroenterology and the Advanced Endoscopy Center in St. Louis, Missouri. He teaches at Barnes Jewish Hospital and is an Associate Professor of Clinical Medicine and Surgery at Washington University School of Medicine. He is a tireless researcher and has published more than 100 articles, abstracts, editorials, and book chapters. He lectures internationally as one of the world's top experts on some things that affect many POTS patients, such as the interaction of GI motility problems, mast cell activation syndrome, irritable bowel syndrome, small intestinal bacterial overgrowth, the use of low dose naltrexone to help some of these conditions, and a few others. He is a medical advisor for the LDN Research Trust, which is where I was lucky enough to find his lectures and then to get to meet him. Thank you so much for taking the time to speak with us today.

00:02:01 Dr. Weinstock: Thank you so much Jill. It's been fantastic journey and you started it as we were traveling from Saint Louis to Massachusetts. We were on the phone for about 2 hours talking about your condition and wondering if LDN could be the answer to your problem. And it was one-third of the problem, answers and came forth, and it's just delight to see you healthy.

00:02:27 Jill (Standing Up to POTS): Well, thank you. And my hope in talking today is that somebody else out there will be in the position that I was in and find even 5% of the benefit that I found from this information. So for starters, Dr. Weinstock, I wanted to read off some of the conditions you've published on and I'm going to challenge our listeners to see if they can spot a pattern in your research. Your work has helped people with: IBS - Irritable bowel syndrome, MCAS - mast cell activation syndrome, EDS - Ehlers Danlos syndrome, ME/CFS - myalgic encephalomyelitis/chronic fatigue syndrome, RLS - restless leg syndrome, CRPS - chronic regional pain syndrome. So I think they get the idea. Lots and lots of syndromes, some of which commonly occur with POTS, which itself is a syndrome. So what are syndromes and why do you study them?

00:03:29 Dr. Weinstock: Syndromes are a collection of symptoms that are characteristic or a problem, and then it may or may not have a specific cause. They may know causative factors in it, but they don't know the root cause, if you will, that could be treated. Just like diabetes; most forms you treat with the medication. It's either, you know, lack of production of insulin or antibodies against it for one reason or another, and you treat with insulin and patients get better. That's a disease, whereas syndromes are something that, number one, when I got out of Med school, I didn't realize that there was so many syndromes because we just were not taught anything about syndromes, at least not that I remember. So you know when I got out I didn't realize boy how dumb we were. You know how challenged were physicians that there were so many syndromes out there affecting so much of the population, like irritable bowel syndrome, 15% of the population has it, and yet it was all lumped together as a set of symptoms. And yeah, people looked at various physiological abnormalities and treated those, but they didn't cut up the pie and say, “OK, this is due to that and therefore it's not really irritable bowel syndrome.” And that actually started in 2000. That's when small intestinal bacterial overgrowth took a big portion of the idiopathic (we don't know what causes it) IBS out of the picture, and in my mind, irritable bowel syndrome caused by SIBO is not irritable bowel syndrome anymore. It's SIBO. And we could talk about just SIBO in a second. But that's the thing. So it drove me crazy. Why were there so many syndromes? Why were we not smart enough to figure it out? And this is also one of the reasons why I went into medicine. It was really a detective work and a challenge, and so that's the fun of what I do.

00:05:38 Jill (Standing Up to POTS): So I wish we could clone you about 1000 times because before I met you, I thought of syndromes as basically the category of medical problems that you just have to live with. I thought you know, “Oh, nobody understands them. There's not much you can do about them.” So before I met you, I had quit looking for answers or treatments for my GI problems because it seemed hopeless and it was just embarrassing to keep talking about it even to doctors. But then some of your findings and your knowledge about gut health were such a turning point for me, about six or seven years ago, and it's not an exaggeration to say that they rescued my digestion, my ability to enjoy eating again, and after years of nausea, crippling stomach aches, bloating after meals, and other GI symptoms that start to get too embarrassing to share, but your findings also helped me with a number of symptoms outside the GI tract, which I hope we'll discuss because this isn't just about me. This is about many people you've seen with POTS and related conditions, and many people I've now seen, and how you figured out that patients like us can be susceptible to this GI problem called SIBO - small intestinal bacterial overgrowth. So, could I ask you to start by just telling us what is SIBO?

00:07:18 Dr. Weinstock: Well, it's a chapter in the textbook, and the reason I start out by saying that is because many doctors say they don't know about it - let's say GI doctors - say they don't know about it. Well, did they not look at that textbook chapter when they were studying for the boards? But I think part of that is they don't want to start opening their minds to say, “OK. A third of my practice - irritable bowel syndrome - could have SIBO. And what am I going to do about it, 'cause I wasn't taught how to treat it in fellowship or medical school?” The information has been there for quite some time and in the chapter it defines what SIBO is, namely it's a certain amount of bacteria in the small intestine that is, well higher leagues amount than is normal, so it's 10 to the fifth colon forming units per CC of bacteria in the gut. And normally we have very few like 1000 colony forming units of bacteria in the small intestine and there are many reasons why our system allows that to keep under control. We have good motility. We have good digestion so we're not feeding those thousand bacteria. We're putting out enzymes from the pancreas that digest the food so the food doesn't get down to the bacteria and feed them and make them grow. We have an ileocecal valve that's good health as opposed to having had surgery for Crohn's disease, let's say, removing the right side of the colon, allowing a big passageway to form between the small intestine and the large intestine. So, when there's a breakdown of a variety of these protective bases, then we get migration backwards of colon bacteria into the small intestine where they can bind to the lining and become adherent and cause damage, and also cause basic fermentation of gases when food comes down there. Or we keep the bacteria out of the upper part of the small intestine by having good acid levels, but if the acid levels are low due to autoimmune conditions like pernicious anemia, then we'll get bacterial overgrowth. Or a number of people taking chronic proton pump inhibitors, the PPI's can have too many bacteria in the small intestine because the acid levels are reduced so they acid doesn't kill the bacteria that are swallowed from the mouth and that goes into the duodenum - the small intestine - and then the bacteria take residence up there. And so the bacteria that grow high in number will do several things: they’ll bind to the wall, they'll stay there forever, the bile that we secrete covers it up and protects it from antibiotics and normal means of probiotics getting rid of it. And so that tenacity of the bacteria will cause inflammation and things we can talk about. And also the food that we eat will be fermented, and we'll get gas and bloating, if it’s hydrogen that's being secreted, there'll be diarrhea, if it's methane that's being secreted, we'll have constipation. And if it's hydrogen sulfide, we'll have a rotten egg smell, and gas that is toxic to our nerves, causing chronic pain, pelvic pain. And also the rotten egg smell may occur, go into the bloodstream, go to the lungs, and will breathe out bad smell, so halitosis can be a factor.

00:11:05 Jill (Standing Up to POTS): So is it correct - we always hear about trying to have more friendly bacteria in our gut, fewer unfriendly bacteria in our gut, but this is a separate problem, right? This is kind of a problem of location more than the type of bacteria?

00:11:23 Dr. Weinstock: Well, it's a bit of both. Location, location, location and bad characters go hand in hand. So basically you're having movement of colon bacteria, especially the anaerobic bacteria, from the large intestine, working their way up into the colon. And that route can be one of two ways: One, there are a number of bacteria at the end of the small intestine, so naturally, just because there's, you know, stool in the right side of the colon, and then there's backflow sometimes of that bacteria. So we do have more bacteria at the end of the small intestine. So they can creep up from there, and those are actually colon bacteria, which are anaerobics and aerobics, and they're toxic to the small intestine, but not to the colon. We have different lining of the colon that allows you to have 13 trillion bacteria there and they do a job and they do it well and it's important that they're balanced. Yes, they have to have good bacteria and that would prevent dysbiosis, kind of a mix of bad bacteria in the setting of the colon. But when we get small intestinal bacterial overgrowth, that's when we have bad bacteria or good bacteria, even from the colon, moving its way up. But again, we don't like colon bacteria in the small intestine. It causes inflammation and damage. And it's so much different than having the same bacteria in the colon, where it belongs. So that migration can come upwards from the small intestine, or what we call the “fecal oral route” if you're not so cleanly and you get bacteria either on your hands or in your food coming down from above, it'll get down in the small intestine, and if you, let's say, have poor motility or muscle activity of the small intestine, then you can set up the condition of SIBO - small intestinal bacterial overgrowth.

00:13:43 Jill (Standing Up to POTS): So this is already sounding a little bit gross, and that's fitting because as somebody who has had all of the symptoms, the symptoms are gross. I know that one of the interesting things about SIBO is how many different symptoms it can cause, but what are the main ones that are on your list to look out for as a sign that somebody might have SIBO?

00:14:04 Dr. Weinstock: Well, this is where it gets interesting because it's not just symptoms, but it's syndromes. And that's the thing that has me excited when I think about SIBO. But basically when we eat a meal, especially high in carbohydrates, the bacteria will start fermenting this and turning it into gas. Now these gases, as I said, with the hydrogen sulfide will occur with any gas, whether it's hydrogen, whether it's methane or it's a volatile gas with bad odor to it produced by colon bacteria in the small intestine. Those gases will do two things: One they will bloat and distend, and it takes time to move that gas out of the small intestine. In fact, 90% of the gas that is formed in the small intestine goes out through the lining of the small intestine into the bloodstream, into the lungs and you breathe it out. That takes time. Whereas only 10% of the gas that we form the small intestine makes it way down to the colon to come out as flatus. So that's one of the reasons why people tell me they look pregnant and it occurs within an hour or two of eating. With respect to bloating, there are different causes for bloating that I think we should talk about at this point, just so we don't blame everything on SIBO. Bloating can occur for a couple different reasons: One would be abdominal pain. Just if you're having abdominal pain almost for any reason, the abdominal wall muscles relax and let basically more space for the gut to be. And it's just basically like overeating at Thanksgiving. You undo your pants and open things up, or in COVID season, you're wearing sweatpants all the time anyway, and it is natural to relax. So bloating can also occur spontaneously and severely from mast cell activation syndrome. We don't know quite why it happens, but it is a true phenomenon and it probably has nothing to do with the amount of gas that you get in the small intestine, 'cause it can be spontaneous and have nothing to do with that timing of bloating after eating a meal. That said, if you're eating toxic things that are activating the mast cells, then those chemicals could paralyze your small intestine large intestine and cause bloating. So, that's bloating gas fermentation. A little bit more, we talked about the role of specific gases. I mentioned their specific roles so it could activate diarrhea, constipation, or just abdominal pain, or in the situation hydrogen sulfide, halitosis, or, if it circulates to the bladder, it may have a role in interstitial cystitis. With respect to interstitial cystitis, which is a very common problem that may be directly related to mast cell activation syndrome. So why not put all of our eggs in one basket and keep our minds open for these syndromes. The other thing that happens is that those bacteria that are increasing in number, they damage the lining, the mucous membrane lining of the small intestine, and some of the bacteria work their way in a little bit and die and release lipopolysaccharides (LPS), which is the outer shell of the gram negative bacteria. LPS creates inflammation under the lining of the small intestine, which brings in the mast cell, which activates chemicals, which brings in the T cells and B cells and T cells produce cytokines, which are inflammatory chemicals. The mast cells produce cytokines, which are inflammatory chemicals, and the B cells produce autoimmune antibodies. Furthermore, all that activity can go down into the nerves that basically infiltrate the small intestine, and the large intestine, and cause pain. So, nerve activation can cause sensory nerve pain connecting to the brain and all these cytokines which I just mentioned can go into the bloodstream, causing systemic inflammation. Think, basically, if you have a certain genetic makeup, you're going to have problems. I know that firsthand and we'll talk about how I discovered my own problem with respect to rosacea, if you'd like.

00:19:10 Jill (Standing Up to POTS): Oh, that's interesting that you mentioned rosacea. I'd love to hear that. And also I was going to say one of the big things I noticed when you treated my SIBO was that I got a new face. I got a new face that was less red, less puffy, and I'm not sure that Facebook would even recognize my face before and after SIBO treatment, and I'm wondering if that has to do with that inflammation that you're talking about. What did you find with your rosacea?

00:19:41 Dr. Weinstock: Well, let me just say. They can tell the pre and post Jill Brook face if they look at the article in the British Journal of Medicine, so it's there before and after treatment, which is quite something. And with respect to personal, do I know that it it's a real thing? Does it work? Absolutely. So, I had food poisoning when I was 18 and again at 20. And then after that food poisoning and the second one, I developed irritable bowel syndrome. I lived with it. I knew certain things that would make it worse: dairy products, caffeine, too much rich food. But I lived with it and you know, it wasn't that bad. But then literally five years ago I started noticing that my eyes were getting uncomfortable as scratchy, itchy, burning, and ultimately I realized, “Oh my goodness, I can't believe this is me,” because this is what I researched in 2011 - the relationship between SIBO and rosacea. But in this situation, it was ocular rosacea for me. And when I had myself tested for SIBO with the Lactulose breath test and I was abnormal and had my physicians assistant treat me, my eyes got dramatically better. I still needed to see my ophthalmologist because I'd let it go on too long and needed more local treatment with drops and moisturizers and so forth, but my eyes got dramatically better. And so the link between rosacea and SIBO exists. The Italians discovered in 2008 for facial disease. I actually did a little study confirming the frequency of SIBO and rosacea and outcomes with treatment, and then did a small study with ocular rosacea as well. And then it's the kind of thing that, you know, years later it hits me in the face, slap your forehead with your palm saying, “Hey, why didn't I think of this sooner?” But, you know, you get busy and you kind of live with things and then it hits you. So, the interesting thing is, I wanted to know a root cause and understand, and I started thinking about this postinfectious phenomenon and this is one of the 40 some odd causes of SIBO, namely when you get a bacterial infection from food poisoning. It could be E. Coli, salmonella, shigella, campylobacter, and even c. difficile, you can get damage to the gut. You can have a reaction by B cells creating an autoimmune antibody, and that autoimmune antibody can then by molecular mimicry, trick your body into making another auto antibody called anti-vinculin V-I-N-C-U-L-I-N. And that anti-vinculin can damage the nerves to the small intestine, creating a situation where you lose your sweeper wave, the migrating motor complex that cleanses our small intestine every night, with this wave sweeping out bacteria old food and keeping the small bowel clean so you're ready to digest the next day. And lo and behold, 40 some odd years later I had positive anti-vinculin levels. Therefore, the root cause of my problem went back to bad mussels and another infection before that where it damaged my gut led to an autoimmune antibody phenomenon.

00:23:43 Jill (Standing Up to POTS): So that's really interesting that SIBO can be initiated from food poisoning, but I think there's some other ways that it can also be initiated right? And some of them unfortunately are more likely to occur in people with POTS and associated conditions.

00:24:02 Dr. Weinstock: Well basically, let's think about SIBO for a minute. It's the bacteria that's not getting out of the small intestine or is accumulating and is getting adhered. Why is it? Well, with POTS patients, there are several reasons why that would occur. Number one, just by POTS alone. If you've got a sympathetic parasympathetic or vagal imbalance, that sympathetic hyper sympathetic tone is going to reduce your peristalsis so that you're not getting the sweeper wave or peristalsis to move the small bowel bacteria out. So that's one of the reasons for SIBO in the POTS patients, and possibly one of the biggest ones. But, also think about the evil triad. POTS, hypermobile EDS, and MCAS. But in that situation, the POTS patients may get the SIBO because with hypermobile EDS you get a loopy, droopy small bowel which can allow like a sewer-like condition, where it's hard for peristalsis to push the bacteria up out of their curve and around and so that is a blind end if you will, which is one of the classic causes for SIBO, usually due to surgery, but nonetheless in this situation in EDS it's due to a loopy, droopy, small bowel. Tough to treat. Sometimes motility medicines work like Motegrity (Transcriber’s note: Motgerity is the brand name for prucalopride) or erythromycin, and sometimes they don't. And then you've got the situation of mast cell activation syndrome, which parenthetically may account for a good third of POTS. And treatment for MCAS can really help POTS symptoms in maybe up to 1/3. But with respect to MCAS, MCAS can cause SIBO, possibly due to the mast cells living next to the autonomic nervous system and causing release of chemicals that prevent the system to be balanced and therefore creating its own dysautonomia by secretion of the chemical mediators. So those are the ways that I see that POTS patients can suffer with the symptoms of SIBO.

00:26:30 Jill (Standing Up to POTS): So that's really a triple whammy of risk factors for POTS patients to be at higher risk for SIBO. So if there are some POTS patients listening to this who are wondering if maybe they have some of the symptoms, what should they do?

00:26:49 Dr. Weinstock: Well, I think it's always worthwhile getting a test to show whether you've got abnormal gases, either one gas or two gas or a mix, because we treat them slightly different. So, hydrogen we usually use something like rifaximin, but also herbal antibiotics. We also want to think about treating the underlying condition whenever possible. Sometimes it's, you know, specifically treating the POTS and hopefully that will improve the autonomic nervous system. Sometimes it's just working with medications to trigger motility, especially at night to cleanse the small bowel bacteria out of your gut. The other thing is like if it's methane or intestinal methane overgrowth, which is the most common pattern as opposed to seeing a peak of methane over baseline, we generally see a plateau and means the methane's being generated from bacteria in the colon and maybe also the small intestine. That's a bit tougher to treat, but can require when it's a high level, two different antibiotics. When it's a medium level, I'll also treat with garlic-based herbals like Allicin or Alli Ultra and Neem plus another herb, or rifaximin or another antibiotic with one of the herbal antibiotics that work against the methane. Sometimes if it's just low levels of methane then I'll treat with the pro and prebiotic. If it's hydrogen sulfide, that's something that is only measured by one particular company’s breath tests, and that company produces a kit called TrioSmart® and that looks for the hydrogen sulfide bacteria in one situation. And that situation can be treated with antibiotic therapy or even oregano. So that could be helpful. So high dose oregano treatment can be helpful. So that's why diagnosis is important. So because I said, you know, you could have bloating for other causes, just because you have bloating doesn't mean you get SIBO or intestinal methane overgrowth. So get a diagnosis with the breath test, if you have high odor of rotten egg then you might want to get the breath test that measures all three gases. If not, you can get any old good breath test that measures hydrogen and methane to look for those gases in excess.

00:29:32 Jill (Standing Up to POTS): So my recollection of the breath test that you're talking about is it's kind of a unique test, and is it correct that the patient drinks kind of a sweet liquid and then exhales kind of into some balloons every 20-30 minutes for a couple hours and then they look to see what kind of gas is in the balloon? Is that is that close to right?

00:29:54 Dr. Weinstock: That's correct, well, there's a couple different test methods. But basically they usually swallow Lactulose. It's not lactose or the milk sugar. Lactulose is actually a laxative, but it doesn't get digested or absorbed anywhere along the GI tract. So when somebody drinks the Lactulose, the bacteria will ferment it and that fermentation product, that gas, will go to the lungs and come out when you breathe. So the basics of it is that you breathe, get a baseline breath and it can go either into a bag or into a test tube, depending on the test kit, and then you drink the Lactulose. Then 30 minutes later you do another breath and then usually every 15 minutes for 90 minutes, although the Trio Smart Company runs about 120 minutes, you breathe and collect samples, send it in to the company or to your GI’s office. Most of our breath tests are done in kits that we send patients home with and get the kit back and run it on our machine to detect when are the levels of the gas going up. So if they're going up within 90 minutes above 20 - above baseline - then that is suggestive of small intestinal bacterial overgrowth. Because the bacteria are higher up in the gut, so they're going to produce the gas earlier on in their test. Now no test is perfect, and we do know that about the lactulose breath test, as if you had rapid transit and delivered sugar to the bacteria in the colon because it went through your system so fast, then you have a false positive test. So that's one of our concerns about it, but if you read the breath test in the right way, and you're convinced that, let's say you start seeing the rises earlier in the procedure, and it's not just at the very last one at 90 minutes, then you feel more secure about having the diagnosis of bacterial overgrowth.

00:32:15 Jill (Standing Up to POTS): So one thing that really struck me about treating SIBO was that it's even treatable. I think some of us we get accustomed to this world of POTS and mast cell problems and Ehlers Danlos Syndrome, and to have something like SIBO come along and cause so many problems and then be treatable with maybe just 10 days or a couple weeks of antibiotics. I know that some people have to work a lot harder than that, and I know that not everybody is a complete success story. But for myself, I was absolutely blown away that I had lived with so many terrible GI symptoms and extra inflammation for probably a decade, and I had only been 10 days of Xifaxan (Transcriber’s note: Xifaxan is the brand name for rifaximin) away from getting rid of it. That just blew my mind. And the other thing that blew my mind was how many symptoms outside the GI tract improved. Things like mast cell flares. Is there a reason why somebody mast cells might be less reactive once you get rid of SIBO?

00:33:24 Dr. Weinstock: Absolutely. Well, when you think about mast cell activation, you want to say, “well where are these nasty mast cells that are uncontrolled, overactive and have mutations that prevent them from getting controlled, and they live longer because of that as well? Well, where do they live?” They live in your nose. They live possibly in your sinuses. They live in your mouth. They live in the guts and also the skin. They live in the bladder and the vagina. So if you think about where they live, they live in the interfaces where the environment can touch them, and normally the mast cells are orchestrators of healing and development and blood vessel development. And they orchestrate other mast cells to behave, and then they orchestrate other white blood cells to behave and do their job. But when they're out of control and they're living in your gut and there's an imbalance of the bacteria there, then it goes back to what I was saying about all those cytokines that are active. cytokines will activate mast cells, so the interleukin and two necrosis factor that are increased by SIBO and likely others will activate the receptors on the abnormal mast cells, which then activate the normal mast cells and that cascade blows up and you get mass cell attacks. And so when you have SIBO, you're constantly activating the gut and if you can reduce that, you can reduce some of the signs of SIBO, but also some of this syndrome. So in a study that we did and published last year, 40% of our patients overall with mast cell activation syndrome had restless leg syndrome and 20 percent of those patients had POTS. So as far as treating restless leg syndrome, antibiotic therapy works, but also naltrexone also is a big winner for patients with restless leg syndrome, whether it's with or without POTS or MCAS. So that's one of the exciting things.

00:35:48 Jill (Standing Up to POTS): So you just said the thing I was going to ask you about next was using naltrexone for some of these problems, and I think that some patients might have heard of low dose naltrexone. Sometimes it gets called LDN. And it's an old generic drug used in a low dose for various things. I think sometimes it has the reputation for being that thing you hear about on the Internet. You met me through the LDN Research Trust. I had been told about LDN by a great pain physician who had recommended it for my pain, and I was very surprised to learn that it can also affect digestion and gut motility and some of these other things. And LDN keeps popping up in your work. Can you tell us what you think of low dose naltrexone?

00:36:48 Dr. Weinstock: I couldn't practice without it, that's a statement right there. A pharmacist told me about the drug in 2005 saying this could help your patients. And so I started reading about it and most of it was about inflammation. So I started using it in my Crohn's and ulcerative colitis patients seeing - I'll stop short of saying miraculous, but I'll say it again - miraculous results for a number of the patients. And if you get 50% efficacy from any drug in inflammatory bowel disease, that's a miracle. Which is the same thing for MCAS and POTS as well as you know. But nonetheless, it's something that I've used quite a bit for irritable bowel syndrome. I have had patients with irritable bowel, who had rosacea who got better with it, psoriasis who got better, variety of skin diseases, sarcoidosis. And I, my practice is, you know, primarily GI as gastroenterologist, so I don't see patients coming in off the street with psoriasis as somebody might do it. But when I see it's on their skin and they're having a colonoscopy, I'll ask them if they're interested in getting rid of it and recommend LDN. And often they do. So that's expanded my experience with the drug. And I literally have prescribed it to thousands of patients for a variety of diseases and then published on them as well. And the drug, what it does is it's important to address this now that it's used in high doses to prevent desire to drink or use narcotics. Used in low doses, it tricks the body into making endorphins. Endorphins increase energy. And endorphins do something else: they decrease overactivity of the T cells, T lymphocytes and the B lymphocytes, so that people who are having autoimmune conditions, if they have perhaps less B cell activity, they may have less autoantibodies. And then if they have less T cell activation, then they'll have left cytokines. And that's important. And then in mast cell activation syndrome, if you can suppress the overactive T cells that can reduce a direct stimulatory effect on mast cells. So then when I looked at 116 mast cell patients, 60% noted improvement with the LDN and to this day when I have a patient coming in saying I ran out and my symptoms came back within three or four days, I say, “OK, that helps prove what's going on.” And then they get back on it and they get back to their baseline. And it's an amazing phenomenon.

00:39:52 Jill (Standing Up to POTS): Does LDN also affect gut motility a little bit?

00:39:57 Dr. Weinstock: Yeah, it can. So, there aren't many studies proving it, but there was a study in humans that they got intravenous endorphin, too, that accelerated their motility. So clinically, I don't think it's the strongest of the motility drugs. Some patients do get a great response with chronic constipation, but not that many, but some do. And then I think when you're getting results in irritable bowel syndrome, a lot of it is reducing the pain - that is, two ways: the endorphins, and also naltrexone directly affecting the cell that sits on top of the nerve sensory nerve cells, so it can affect the inflammatory nerve response.

00:40:46 Jill (Standing Up to POTS): And I know from some of your presentations, you've shown photographs of people’s intestinal walls before and after using LDN, and some of these photos are just shocking.

00:40:58 Dr. Weinstock: To some degree, yeah. So I mean, it's a matter of being willing to try things that are different. Now, with respect to your audience, when you go to your physician and say I'd like to try LDN – naltrexone - it's going to take some education because there's no drug company out there educating the doctors for this. We do have information in the LDN book, two LDN books, and their references there and there are references that you can easily look for on Google Scholar. It's very easy to negotiate. But part of the problem is that this is an FDA approved drug, but for different conditions. Plus you're using it in doses that only in general only compounding pharmacies can formulate. Doctors can write for it and can get it anywhere but it's a lot of the times as the doctors are in a stuck mode. If they're not educated about it in their residency or fellowship, or a drug Rep hasn't come in and said, “OK, this is a new drug you want to try it? This is how you prescribe it,” it doesn't go anywhere. But in fact, this business of prescribing a medicine that's off label is a legitimate phenomenon that's done every day when, let's say, doctors are prescribing Prilosec twice a day for severe reflux. That's not on label, the FDA doesn't approve of that. So they're doing off label prescribing. So when you're doing off label prescribing, you're dealing with something that is a little foreign to some doctors, but in the fact is that many of them are doing it without even knowing.

00:42:47 Jill (Standing Up to POTS): Well, and in my speaking with some dysautonomia patients who were seeking a SIBO diagnosis or treatment, they have mentioned that they struggle sometimes to find doctors who are familiar with SIBO. So it sounds like this just isn't that widely known yet. Is that correct?

00:43:04 Dr. Weinstock: You know, LDN - 400,000 prescriptions per year for LDN, so that's not minor. That's significant, and you can actually get a prescription online through a doctor has multiple licenses or with the LDNResearchTrust.org or LDNScience.org, you can find doctor in your own hometown that is prescribing LDN and knows about it. With respect to Knowing about SIBO, as I said, I think more and more people are learning about it. I mean, they should know about it because in 2015, Xifaxan (Transcriber’s note: brand name for rifaximin) was approved for the treatment of irritable bowel syndrome with diarrhea. What is SIBO? It’s an overgrowth of bacteria. What is Xifaxan? It's an antibiotic. So the FDA has approved use of an antibiotic to treat irritable bowel syndrome. What a number of people don't understand is the poor motility and why it's so important to address that, often with promotility drugs. And a lot of people don't know about the anti-vinculin antibody at this point. If you want to really diagnose and say, why does the patient have it? But with it, POTS and MCAS, I think that if the POTS and MCAS patients are being cared for by a specialist, then those specialists will often know about SIBO and can direct treatment and can order a breath test, or could defer back to a gastroenterologist who is up to date. Now, 2015-2021, we’re talking about six years of a drug being on the market to treat irritable bowel syndrome. You'd think most GIs would know about it. And that in fact, the SIBO is the underlying cause. So I think that often you'll be able to find somebody.

00:45:13 Jill (Standing Up to POTS): We have covered a ton of information, so if we were just going to summarize quickly for somebody who's hearing about SIBO for the first time, is it correct to say SIBO is when bacterial colonies from your colon or elsewhere can set up camp in the small intestines where they're not supposed to live? And when they're there, they can cause inflammation. They can steal your nutrients, they can cause bloating, gas, stomach aches, and all kinds of problems and that POTS patients for several different reasons may be more likely to get SIBO? However, that it is treatable, and if they find that doctor who is familiar with it, there's a lot that can be done to actually get rid of SIBO. This is one thing that's actually curable for many people, right?

00:46:03 Dr. Weinstock: It's definitely treatable. In terms of long term care, I only see a few patients who take one round of antibiotic and then let's say get on a probiotic and they're better. But I just saw one this past week. Nonetheless, if you can address the underlying cause and treat that and treat the bacteria, then you can get a prolonged remission with rare to occasional relapses. I wrote an article about using antibiotics for retreatment, but also looking at prolonging the duration of symptom free without SIBO for over a year and a half, just by low dose azithromycin 50 milligrams at bedtime, which emulates a gastrointestinal hormone called motilin, which stimulates small bowel motility. So, you know, there's ways to manipulate the gut. There's ways to tone down your mast cells so that they're less apt to paralyze your small intestine. And theoretically, there's ways to treat your POTS specifically. There's just an article recently about Losartan affecting the autonomic nervous system autoantibodies and improving POTS in that regard. It’s a blood pressure medicine, which could be tricky to use in POTS patients. But again, if you've got this specific autoimmune antibody, this is really, really exciting, so you know it's something to think about. Or in our IVIG patients, you're capturing the autoantibodies and you're reducing the POTS and getting better balance between the sympathetic and parasympathetic autonomic nervous system. And I think about one of my patients that I put on IVIG. She saw me, basically I went through my EMR listing out 18-19 problems by diagnostic codes and she went on IVIG and got treated for SIBO and she's now graduating nursing school and is having a productive life and went from looking so ill, so ill, to being a healthy looking 21 year old woman. It’s amazing.

00:48:25 Jill (Standing Up to POTS): That's great, is there anything else you think POTS patients or their caregivers or physicians should know about SIBO or syndromes at this point?

00:48:31 Dr. Weinstock: I think we covered a lot of them. I think that you have to realize that it may require more than one course of antibiotics or altered antibiotics. We want to avoid antibiotics that put you at risk of C. difficile - the overgrowth of Clostridium difficile, the bad bacteria that causes diarrhea. So I'll never use quinolones like Cipro or Levaquin (Transcriber’s note: Cipro and Levaquin are both antibiotics) to treat SIBO patients. I try never to use Augmentin if possible, but if, let's say rifaximin doesn't work, I'll try herbal antibiotics, something that I've learned from naturopathic college presentations and that can be helpful. And then I will try as much as possible to look for the root causes of SIBO that are treatable. So, you know, we have like over 40 disorders that can cause SIBO. Not all are treatable, but if you can find them, that's great. So like people have lost their acidity or, you know, they can take literally acid pills, if they have POTS and can be treated specifically, they may have less SIBO after you treat it with antibiotics. And in mast cell, if you can control the mast cells, any number of the cocktails we use for mast activation syndrome, then again, we may have a prolonged relief of SIBO after antibiotic therapy.

00:50:08 Jill (Standing Up to POTS): So this is fantastic information, and obviously there's so much more complexity that we don't have time to get to, but I hope this gives people enough to go on to maybe start learning about it, and if they think it's relevant to them, that they can find an expert who can help them along and see if they can maybe make some progress along these lines. To listeners, if you want to hear more from Dr. Weinstock, just Google his name, “Dr. Leonard Weinstock,” and you'll find lots of great interviews, PowerPoint presentations, publications, so much wonderful information. As you can tell, he is a powerhouse of progress and knowledge. And Doctor Weinstock, I cannot thank you enough for taking this time with us today and for working on finding better answers about tough syndromes. I have to say that getting to share your findings with POTS patients is actually one of the big reasons why I wanted to be a part of this podcast in the first place, because I know there will be somebody out there for whom this information will help them a lot as it helped me. It just changed my life completely and we're so lucky to have your brain power working on our problems. So thank you for that, and for your dedication, your empathy, and for everything you do. Finally, as always to our listeners, remember, this is not meant as medical advice. Consult your medical team about what's right for you. We are all different and goodness knows there are many more GI issues in POTS besides the one we discussed today. But thank you for listening. Remember, you're not alone. And please join us again soon.

00:51:48 Announcer: You can find us wherever you get your podcasts or on our website, www.standinguptopots.org/podcast and I would add if you have any ideas or topics you'd like to suggest, send them in. You can also engage with us on social media at the handle @standinuptopots. Thanks for listening and we hope you join us. This show is a production of Standing Up to POTS. (Transcriber’s note: if you would like a copy of the transcript for this or any other episode, please email volunteer@standinguptopots.org) © 2021 Standing Up to POTS. All rights reserved.