Welcome back to another episode of The SIBO Doctor Podcast. I took a little bit of a break over the last few months, and it's great to be back on the air again. We've recorded episodes for The SIBO Doctor Podcast for the last four years, so it felt a bit weird to be off the air, but needed it just to rejuvenate and get some of the creative juices flowing. I want to thank all of you who have written in and suggested some fantastic podcast topics, and we'll... Thanks to you, we'll have some great topics coming up. It's not too late to send us your suggestion. You can email us at [email protected] if you have a great guest that would be wonderful to have on the air to discuss SIBO and other digestive disorders.

Nirala Jacobi:

Today's episode is about hydrogen sulfide. We had a lot of requests for this. Hydrogen sulfide SIBO and LIBO. LIBO standing for Large Intestinal Bacterial Overgrowth. My guest is Dr. Joshua Goldenberg, who is a researcher, teacher, naturopathic doctor, and founder of the Dr. Journal Club. He's an active researcher with numerous prestigious publications, and his research focuses on SIBO, irritable bowel syndrome, evidence-informed practice, and research methodology. He is a research investigator at the Helfgott Research Institute and Visiting Research Scholar at the University of Technology Sydney. He lectures widely and currently teaches post-graduate students at Helfgott in advanced evidence synthesis methods. Welcome to the podcast, Dr. Goldenberg. Really nice to have you on the show.

Joshua Goldenberg:

Thank you so much. It's a real pleasure to be here, Dr. Jacobi. I've been excited about this podcast for a while. I'm a fan. Actually, I was a bit of a podcastaholic for a while, I was like... Then, I found Audible, and so the only podcast I still do... This is not me, just me kissing up. It's truly The SIBO Doctor Podcast because I feel like I have to for my profession.

Nirala Jacobi:

Thank you.

Joshua Goldenberg:

Just stay up to date, hear what the latest stuff is, et cetera.

Nirala Jacobi:

Well, thanks so much. Really, the topic today and the reason I thought you'd be a fantastic guest on the podcast is hydrogen sulfide. We get so many questions about the hydrogen sulfide, and there's a general confusion around this whole topic. I don't think it's just SIBO patients. It's gut patients in general. Even researchers are confused. So I thought we'd take a moment and begin the podcast with really defining what we're talking about. You are an expert in IBS and SIBO, and we will get to your study that you're conducting as we move along because it's a really important study for practitioners. So I'm super excited about that. So let's get started with talking about... really defining hydrogen sulfide SIBO. What are we talking about?

Joshua Goldenberg:

Yeah. So I know we are supposed to talk about this at the end, but I think it's relevant at the beginning. So who the heck knows? I think that's the big question like, "What is the definition here?" What you'll see out in the community, what doctors are doing is pretty much falling into three buckets of definitions, right, and how they're making that diagnosis, how they're making that definition. So one is basically, you're actually measuring hydrogen sulfide, right? So you've got SIBO symptoms, you have a patient come in, you get a test that can actually measure hydrogen sulfide, and you're looking at a threshold. We should actually talk about thresholds because that's been changing based on some new research on that.

Joshua Goldenberg:

The other has been used for years, which is the flat line hydrogen, the third hour, right? So you do a lactulose test for three hours. If you see a flat line, and we could talk about why we think that is, the idea was, "Okay. That might be hydrogen sulfide. These patients have hydrogen sulfide SIBO." Then, the third is empiric. There's been a bucket of symptoms that clinicians suspect are related to hydrogen sulfide, and if people meet that criteria and still feel SIBO-y, then we put people in that bucket. So that's how doctors have been making those diagnoses and how they've been using those definitions. I think these are different ways of defining or making a diagnosis for this idea that you might have an overgrowth of bugs in your gut that are overproducing hydrogen sulfide, and that's what's causing a problem, right? That's the idea behind it anyway.

Nirala Jacobi:

I think one of the reasons everybody is so confused about it is that there really are no way of absolutely knowing whether or not somebody has this condition, unless they utilize this one lab in California called Gemelli Lab that does the Trio-Smart Test that looks for hydrogen sulfide as well. That's a relatively new test, and to be honest, a lot of patients that I suspected had hydrogen sulfide came back negative with this. So there still needs to be a lot of hashing out what the criteria are, and so I do think it's important that we get more research in this area, but I think one of the... Just to clarify for the listener who've been tuning in for many years. We know about hydrogen SIBO, which is an overabundance of bacteria that produce hydrogen, and those are usually Klebsiella and E. Coli as it turns out. Then, we have methanogens that produce methane, but we are re-thinking that whole diagnosis as more intestinal methanogen overgrowth rather than classic SIBO.

Nirala Jacobi:

Then, we have this third category of hydrogen sulfide SIBO, but also LIBO, which we'll get to later, which is more large intestinal hydrogen sulfide production, but that's all... Hydrogen sulfide SIBO has always been very elusive because we have no way until recently of really measuring hydrogen sulfide because it's such a... My understanding is it has such smaller reference ranges and very difficult to detect, and so there's only one lab that has created a test for this. Also, the diagnostic criteria for hydrogen sulfide SIBO, traditionally, my understanding is where mostly really severe diarrhea. Then, we have research that actually looked at colonic production, so much further down, of hydrogen sulfide, and they cause constipation. So can you talk about what the classic symptoms are that we're actually looking for when it comes to hydrogen sulfide in general, and what should we look out for, constipation or diarrhea?

Joshua Goldenberg:

Yeah, yeah. So okay. Awesome. So there's so much to talk about there. Okay. So I think you're referring to... There was a validation study out of the Cedars-Sinai, and it's presented at EDW this year that essentially had three groups of people, right? You had healthy controls, you have people with diarrhea, IBS, so that was Rome 4, IBS-D. So diarrhea sub-type of IBS. As you know, Rome 4 is very strict. You have to have pain, and a lot of C patients with SIBO that probably don't meet Rome 4 criteria. So that's one relevant piece, and the other was IBS-C by Rome 4.

Joshua Goldenberg:

So in that study, what they... and they looked at hydrogen sulfide levels. What they were able to show is that using a threshold of five parts per million, the people with IBS-D clustered very, very differently than people with IBS-C and healthy controls. It's quite clear, right? So if you see the... I'm moving my hand as if that your listeners can see me, but if I can describe it, so... and you pretty much have a cluster of healthy patients between one, two, maybe three parts per million. There's a few scattered points, but that's essentially where most people lie.

Joshua Goldenberg:

Constipation is like all over the place. Again, this is IBS-C, constipation, and then IBS-D really clusters up around five and above. So what they showed through that is that using hydrogen sulfide tests, you're able to differentiate with various statistically significant [key vow 00:09:50], which just means we think it's a real thing, not random chance. We're able to differentiate people with IBS-D, with diarrhea from others, and so that's the idea. This got this reputation for being diarrhea predominant, right?

Joshua Goldenberg:

Now, what's interesting is like clinically, that's not what I've been seeing. That's not what a lot of clinicians have been seeing. A lot of us have been seeing constipation, and it's been this issue because you go to the website of the company, and it talks about diarrhea. If you're asking another practitioner to order it, and maybe they're not familiar with it, they get a little bit confused or patients get confused too, but what's interesting is... So one of the things that we're doing right now... So two things to say about that.

Joshua Goldenberg:

One is... and we'll talk about it more in a second, but we're doing this hydrogen sulfide registry. One of the things, the reason for that is to get a sense of what are all the symptoms associated with hydrogen sulfide diagnosis. So we've got a list of like 20 different symptoms. We can go through them, but what's fascinating so far, a hundred cases in is like constipation is beating out diarrhea as far as what clinicians are putting in. So clearly, constipation, out in practice, we're seeing that a lot at least I these hundred cases. We're seeing them more than diarrhea when we're making these hydrogen sulfide diagnosis.

Joshua Goldenberg:

So that's in the case registry that we're doing, and then if you look at the more formalized research, that validation study, if you look... and again, remember, this is IBS-. So again, it's a very strict definition of constipation, but in that group, the constipation patients, their parts per million hydrogen sulfide were all over the place, like it was really... It did not cluster tightly at all, and so I feel like you're still seeing people with parts per million over five that have constipation. So it isn't so surprising. So maybe that's a long way around saying, "I don't know if it's always diarrhea predominant." I, personally, in clinic, have seen it a lot where it's constipation. Our case registry is bearing that out, and I think the... If you dive in to the validation data a little bit, even though the headline is it predicts diarrhea, that isn't the full story there.

Nirala Jacobi:

So I think it's a good time to talk about your registry, and what you're hoping to accomplish, and really, a call to action for all practitioners out there. We need your help to define what you're doing. How are you diagnosing? Well, I'll let you talk about this.

Joshua Goldenberg:

Yeah. Sure. So let me give you a quick fun example. So what would be the number one... If someone said, "Hydrogen sulfide SIBO," to you, right? What would be the number one symptom, the classic, pathognomonic symptom that you would call out? What do you reckon it would be?

Nirala Jacobi:

Well, like I said, if it was SIBO, I would think... From what I've learned through Dr. Pimentel, I would say diarrhea. But as you've just confirmed to me, that's not what I'm seeing either, but I'd probably say burning bladder syndrome or sort of like...

Joshua Goldenberg:

Yeah. Okay, guys. Yeah, yeah. So burning.

Nirala Jacobi:

Yeah.

Joshua Goldenberg:

What else? That's classic.

Nirala Jacobi:

I think that will be the number one.

Joshua Goldenberg:

Number one? Okay, cool.

Nirala Jacobi:

Yup.

Joshua Goldenberg:

So, see...

Nirala Jacobi:

I'd say rotten egg gas, right? That's what we all are told.

Joshua Goldenberg:

Yeah, that's why [inaudible 00:13:05]. Yeah, sort of pathognomonic. It's like, "Oh, it's going to be sulfur. It smells like eggs."

Nirala Jacobi:

Yeah.

Joshua Goldenberg:

That's, I think, very interesting example because... and that's why we went into the registry, and so I'll come back around on the back end. But essentially, there's all these things that we've been taught about hydrogen sulfide, and a lot of them are... Well, they're all anecdotal. We have very little research on it, and a lot of them, when you have anecdotes, a lot of it is, "What's cashie? What makes sense? What's get passed on from one clinician to another?" The thought is, "if we can actually start mapping out what people are seeing, like successful case or not successful case?" Right? So it's not people presenting their brilliant piece of work where they cured someone in two seconds, and it was the most genius combination. We want the good cases and the bad cases. We want to get a sense of what's going on.

Joshua Goldenberg:

So I had this sense in my mind of that classic symptom, the rotten egg smell and rotten egg burp, or flatulence, or whatever. It turns out you could do this registry, and it's essentially like a very, very small number of the cases, at least the first hundred or so that we see where it's like bloating. Abdominal pain is really high. Constipation, like I said, is really high. Diarrhea is up there too or way, way higher, right? So it just goes to show that what we may consider pathognomonic may actually be quite rare. So, anyway. So what is the registry?

Joshua Goldenberg:

So essentially, what a case registry is, is a way to prospectively capture clinicians' cases, right? So essentially, the thought was we have this new machine. People have been working with hydrogen sulfide SIBO for a long time. You've been coming up with approaches. SIBOC have been coming up with approaches. Most of us are following you guys, right? You guys have been doing it for a long time, and it makes tremendous amount of sense. The thought is like, "Well, finally, we have this machine that's actually capturing, we think, parts per million of hydrogen sulfide."

Joshua Goldenberg:

Essentially, you have hundreds of practitioners doing experiments every day where they're measuring gas levels they're treating with herbs or they're treating with drugs. They're capturing symptoms. They're tracking responses. What if we could actually gather all this data in and look for signals? Right? So this form of research is very high... We call it high risk of bias. It's low-quality evidence because who's putting it into the registry? Maybe you don't put in your cases that you don't want to put in. Put in all of them, right? But maybe people aren't. So it's prone to bias.

Joshua Goldenberg:

That being said, it's like a really good first step, and the thought is if we can a signal like, "Wow," like all these people are recording constipation, right? That's interesting, right, or everyone is using this method like, "Huh, that's interesting. We should look more into that." Right? So looking for these really blaring signals to us, we could then use those in more formalized low risk of bias studies like randomized control trials to actually study it. So it's a way of gathering this data. What's exciting is if we can get 400 cases. We've got about a hundred cases now. So if we can get to 400 cases, you're going to be able to statistically look at second order of things. So, for example, and you'll need to shut me up because I just get really excited talking about this, but like...

Nirala Jacobi:

No, keep going. This is very good.

Joshua Goldenberg:

All this information we need to know, right? So you asked in the beginning, "How do you define it? How do you make those diagnoses?" So we have these three buckets, right? Empiric diagnosis, flat line hydrogen, and we have the hydrogen sulfide levels. So the question is, what if what we've been considering hydrogen sulfide all this time with these flat lines and empiric, what if they're different than what we're calling hydrogen sulfide now with high parts per million hydrogen sulfide? Right? What if they're actually different phenomenon or different phenotypes of the same condition? What if they respond differently to interventions? Right?

Joshua Goldenberg:

I think you've talked about this, right? So large intestinal hydrogen sulfide producers, those may be different bugs than the ones we think they're doing it elsewhere. Maybe they respond differently to different interventions, et cetera. So if we get enough cases, the idea is, "Okay. If we take all these cases and we divide it up into people that made the diagnosis based on empiric, and then we take all the cases that made the diagnosis based on flat line versus this, and then if they used bismuth in one, two, three, which one did better? Who's recording better responses? Are all the hydrogen sulfide cases that are parts-per-million-based tough responders? Right? Is the prognosis different?"

Joshua Goldenberg:

So this is fascinating to me, right, because we've just been guessing at what hydrogen sulfide is all this time, and we're still doing it. Now, we just have a fancy machine that does it too, and this will, should, I hope, help guide us. I think clinically, the most important thing to me minus the validations of all this is it needs to be clinical-outcome-based. Right? So it's less important to me, how tight their... Is it five decimal points of parts per million? I don't care. I want to know if it's over a threshold, and I give X. Can I expect the patient to get better or not? Right?

Nirala Jacobi:

Mm-hmm (affirmative).

Joshua Goldenberg:

That's what matters.

Nirala Jacobi:

Mm-hmm (affirmative).

Joshua Goldenberg:

So the idea here is to have it really be clinic-outcome-driven, and then use that in a randomized design.

Nirala Jacobi:

That's great, and the link to this case registry will be in the show notes. So, practitioners, have a look there. There'll be more explanation on your website that the case registry is on, and I wanted just to back up a little bit to clarify because I know a lot of listeners heads are swimming because not everyone is a practitioner. But I just wanted to clarify that what we're talking about is that there really isn't a very good diagnostic test for these different phenomenon that we're seeing in terms of is it actually hydrogen sulfide SIBO? We don't know. Is it hydrogen sulfide LIBO? We don't know. We're going by stool tests that are also very limited by looking at one or two bacteria that are very specific for hydrogen sulfide production like desulfovibrio and bilophila. But it turns out that there are a host of other bacteria that can upregulate their pathways of hydrogen sulfide production if the conditions are right. Right?

Nirala Jacobi:

So I think we oversimplified it with that model, and I feel like we all need to take a step back and think about before we diagnose somebody with hydrogen sulfide that we really don't fully know. The other one that you... I think what I would've said, what's the other hallmark of a hydrogen sulfide patient perhaps is this sulfur sensitivity. Now, sulfur sensitivity may not be due to hydrogen sulfide overgrowth. It might be a thiol sensitivity, and the rotten egg smell gas may not actually be rotten egg. It might not be hydrogen sulfide. It may be methane thiol. So there are so many complicating factors, and I just commend you for trying to at least shed some light on this complicated issue that I think practitioners tend to simplify just because otherwise, it's too overwhelming to treat to be honest.

Nirala Jacobi:

So it's really good that we have some way of tracking some of this because I think you're absolutely right. I think we will find there are different conditions. It's not as clear-cut as just, "Well, let's rubber stamp this one for hydrogen sulfide SIBO." It may be that they have certain transsulfuration pathway snips that don't allow them to process stuff. We've talked about this before, but yeah, it just gets really complicated.

Joshua Goldenberg:

Yeah, it totally does, and it's interesting. So a quick aside, the sulfur sensitivity is also one that's less than 20% of what we're seeing, right?

Nirala Jacobi:

Oh, really?

Joshua Goldenberg:

Yeah.

Nirala Jacobi:

Wow.

Joshua Goldenberg:

So it's one of those fun examples where, again, it's a case registry. It's prone to bias, but it's the best we have, about a hundred cases combined, where it's a very small percentage actually of reporting sulfur sensitivity, which is interesting. So again, maybe pathognomonic, but may actually be quite rare. We'll have to see in more formal research, but that just points to the fact that it's just very hard to make these calls based on symptoms.

Joshua Goldenberg:

So, yeah. No. So I couldn't agree more, and I think the corollary to the problem that we had years ago, where it's like we had no way to formally objectively measure it and we were going based on symptoms of flat lines is now we... I think we run the risk of being overly scientific, right? We have all these precision with this new tool, but does that translate to clinical precision, right? So that's a question, I think. Just because we can see it on a graph now, do we get overly enamored with that? Can it be a red herring? Do we need to pivot or bail sooner in clinical approaches?

Joshua Goldenberg:

So that's a big question in my mind, and I worry as we have this very objective measure and a very solid test. The question is, "Okay. Are we going to become overly enamored with it?" which will be interesting. So, yeah. I think either way, we know next to nothing about this. But based on formal research, it's all clinical anecdote at this point and some very, very basic research, which is fine. It's a start, but we really need formalized approaches based on clinical outcomes to drive this feel forward. I mean, I'm sure you see this with patients. There are some patients I get where it's like, "Man, we've been at it for a while, and it feels like we're going in circles. Yeah, we're knocking this off and crossing this option off, but it's like how many more options do we have to cross off here, and how long are we going to spend down this rabbit hole before we pivot?" These are just really important pragmatic questions that hopefully we can get a little bit closer to answering.

Nirala Jacobi:

Well, you've already blown my mind and that basically, none of the symptoms that we've always preached were hydrogen sulfide related. We're in the top 10 of the people that knew registry.

Joshua Goldenberg:

Yeah.

Nirala Jacobi:

So what would you say are the top 10 or the top five if you don't remember them all, but what are the most...

Joshua Goldenberg:

Yeah.

Nirala Jacobi:

What are people saying they find highly associated with hydrogen sulfide? A followup question, how are they diagnosing it?

Joshua Goldenberg:

Okay. Great. So right now, I think the main... Again, it could change over time. Hopefully, after this podcast, we're going to have another 200 cases, which would be great. So I think right now, we're seeing the classic SIBO stuff like bloating, discomfort, things like that. We're seeing a lot of constipation, a lot of diarrhea. Constipation is winning out, but diarrhea is up there too. Abdominal pain is a big one, which I find very interesting because of the visceral hypersensitivity connection that we think with hydrogen sulfide, which is very interesting. We're seeing some of the urinary symptoms. Some of the skin manifestations, some of the nerve manifestations, but these are, at least currently, low counts, and then the classic sulfur, egg smelling. Flatulence and burping are much lower as well.

Joshua Goldenberg:

So, yeah. It will be interesting, and then... Sorry. What was the second half? Oh, how are they making the diagnosis? Right now, it's split. About a third, a third, a third, which is great. I think we're getting loads of different data sources. A third of people are making that diagnosis based on parts per million Trio-Smart, a third empiric, and a third based on flat line hydrogen, the third hour, and what I...

Nirala Jacobi:

Yeah, so I've got a few things to say about that because like I have... If somebody with these symptoms that you just listed, which could be just practically anything IBS-related, right?

Joshua Goldenberg:

Mm-hmm (affirmative).

Nirala Jacobi:

Bloating, hypersensitivity.

Joshua Goldenberg:

Yeah, yeah.

Nirala Jacobi:

That, to me, does not scream hydrogen sulfide at all, and if somebody... I will just say that in my experience with working also with practitioners, there's still a lot of confusion around what actually constitute a flat line. I've seen a lot of people in chat groups and forums talk about that it is flat line. They show the test, it's not a flat line, right? So I think there is also a bias that when somebody does a SIBO test, they will... We are just not willing to accept that sometimes patients are negative on a SIBO, on a breath test. So that's also in there?

Joshua Goldenberg:

Yeah.

Nirala Jacobi:

So I just wanted to bring that up because that would be challenging for me if somebody made an empiric decision that this was hydrogen sulfide.

Joshua Goldenberg:

Totally.

Nirala Jacobi:

Although, if they then get a really good result with their treatment, then, of course, that stands to reason that there was a component of that.

Joshua Goldenberg:

Well, maybe, maybe. What if they used Rifaximin for treatment, right, and actually, it was hydrogen SIBO all along, right, and they got better? So we don't know, and the problem is like... So with this registry, by definition, it's clinicians making that call, and we may disagree with how they make that call, and we have questions that try to capture that, so we have... For example, if they make the diagnosis based on a flat line, did you use lactulose or glucose? Right? So we know that you should be using lactulose there, but that's an important question. Do we need to throw some of these out because that would, obviously, be a flat line, right, if it was glucose. How many hours did you do the flat line for, and what was the peak level in the third hour? What was the peak part per million?

Nirala Jacobi:

Yeah.

Joshua Goldenberg:

Right? That's already fascinating. We're seeing a really tight cluster around that right now, which I think is good. Does that mean that's the right answer? No. But does that mean that at least out of a hundred cases that clinicians are pretty consistently picking the same numbers? That's interesting.

Nirala Jacobi:

That's great.

Joshua Goldenberg:

That's interesting to me, right?

Nirala Jacobi:

Mm-hmm (affirmative).

Joshua Goldenberg:

Then, also, again, if we get to the 400 level or things like that, we'll be able to tease these apart and say, "Okay. Well, you were making that diagnosis," because we'll be able to link these symptoms too, right? So, okay. You made a hydrogen sulfide empiric diagnosis, and the symptoms were constipation. Interesting, right? So maybe in some secondary analysis, we'd say, "Well, Nirala would not be cool with that." Maybe we separate those out and see Nirala kosher versus Nirala unkosher stuff. Do you see a different response? Right?

Joshua Goldenberg:

That's the power of having a large dataset, where you can do those secondary tease it apart, and it could be that we're all wrong. Maybe it doesn't matter or maybe flat line is way higher than we thought. So the idea is to gather that information, but to underline what you said, it is... The registry is only as good as the cases that are put in there, and so we don't want your hero cases. We want your successes and your failures. We want to know what's the success rate here. We want to know what do these things look like. If you make that diagnosis, we want to know how it went and how you made that diagnosis. So, yeah. We may disagree in how we make that diagnosis, but like we said, right now, we have no clue how to formally diagnose it. Hopefully, this gives us some sense.

Nirala Jacobi:

That's a really good point. I mean, we just need to collect the data. Also, patients listening to this who were diagnosed with hydrogen sulfide, I encourage you to go back to your practitioner and encourage them to register your case. It's anonymous, so you will not be named, but just so that we can gather data because we have literally just a handful of therapeutics also that... Besides bismuth, we've got the oregano oil. We've got the zinc acetate. In terms of natural therapies, it's been really refractory to treatment so... and the vegetarian diet.

Nirala Jacobi:

I do want to say that I find that... Personally, I think that I mentioned that in Instagram somewhere on a study that that really showed to me that besides... Let me rephrase this. When people are sensitive to sulfur-containing foods like broccoli, and garlic, and onions, that could actually be not hydrogen sulfide related. That could be related to more of like a thiol sensitivity. So when people are sensitive to those types of foods, that may be different from hydrogen sulfide. But then, if you actually put them on a vegetarian diet where they remove all... because meat is the highest driver of hydrogen sulfide in this study that I read. I don't know if you agree with that or not, but it seems to correlate with the patients that I see with hydrogen sulfide.

Joshua Goldenberg:

Okay. So I'm going to ask you on air. Okay. So this is so important. So therapeutics and low-sulfur diet. So, for example, so in the registry, quickly, what became apparent was there are three winners in treatment. So of all the treatments we listed and every time people kept on populating it with others, we put that in as well. The three far and away winners are bismuth, oregano, and low-sulfur diet. Right? Not a big surprise to us. So that doesn't mean they work. It just means that clinicians are using them a lot.

Joshua Goldenberg:

Already, this study, which has only just begun, is already [sponning 00:30:52] two new studies. So, right now, we've begun design of a scoping review on low-sulfur diets, which I want to talk to you about and see if I can rope you in on air for, and the other is a safety study on bismuth. So I use bismuth a lot personally with hydrogen sulfide patients clinically. Anecdotally, it seems to work very well for me, but it always makes me nervous. I know the safety studies and all this, but ti's like, "Uh, I don't know. How long can I use this stuff? How high can I go? It seems to need to go pretty high for a long time. We sure that's cool? What if it comes back? How many rounds?" So I just wanted to know more about the safety perspective of this.

Joshua Goldenberg:

So we've got a toxicologist. We're putting together a doctor in pharmacy. We have a great research team to do a systematic review on the safety and adverse events of bismuth, different types of bismuth. So that will be useful I think in the literature. If we're all using this, we need to know more about the safety of it. Then, for low-sulfur diets, what the heck does that mean? I know you've got a low-sulfur diet, and I want to talk to you about that, and it's like, "What does that look like? What does the literature say?" So we're in the middle of a scoping review on that to get a broad sense of what's out there on a low-sulfur diet. To your point, at least the data I've seen is on vegan diet. So a vegan diet easily has a third less sulfur than a standard diet, and so what is a low-sulfur diet? Is that equivalent to a vegan diet? In which case, is it just vegan diet, or is it a vegetarian diet, or is it low-sulfur means you have to go even lower than that? Right?

Nirala Jacobi:

Yeah, yeah.

Joshua Goldenberg:

So, yeah. So I don't know. So that's the idea behind the research. We'd love to have you on board as the content expert actually if you're available. We'll keep your time limited, but we would love your expertise on that because I know you put... I'd love to hear it. I'd love to hear more about your thoughts on low-sulfur diet. It's top two on interventions that we're seeing.

Nirala Jacobi:

Yeah. Look, I'm happy to help you in any way I can. From what I know, I do think there... I had this really great conversation with Greg Nigh, who was a podcast guest, and he talked about kale being the number one food that he found to be quite reactive for people with sulfur issues. I mean, I haven't seen that per se. I think that there is a category of sulfur-containing foods that are, in general, reactive for some people, which I suspect is not necessarily hydrogen sulfide, as I mentioned. They're a thiol issue. So maybe more along the lines of... These people are also sensitive to other thiols like glutathione, and NAC, and stuff like that.

Nirala Jacobi:

But generally, I think what I usually do is I do put them on a vegan diet, and I tell them to reduce their sulfur foods for a month only, right? So that's easy to do. It's not hard, and that gets usually pretty substantial results. Not constipation resolution. Sometimes, not typically, but it's more bloating, and reactivity, and bladder pain, and burning symptoms in general tend to really respond to that. I'm happy to contribute in any way I can with that. The question I had about the bismuth because I'm curious about that is there are lots of different... Well, there's what? Bismuth subsalicylates. There's bismuth subgallate, and there's bismuth subnitrate. Which one are you using?

Joshua Goldenberg:

Yeah. Okay. So the registry is capturing all of them, right? So if someone clicks "Bismuth," the next thing down is, "Okay. What type? Are you using Pepto-Bismol? Are you using it from Phase 2, et cetera? Are you using subnitrate, salicylate? What are you using?" Then, also, the milligram amount of the bismuth is captured next, and then the length of time. That's interesting too. We're seeing a bimodal distribution. So people going really high on bismuth and some people going relatively low on bismuth, which is curious to me. Not so much in the middle. It's either like you hit them hard or you go gentle, it seems like. So, yeah. So I think people seem to be using things across the board.

Joshua Goldenberg:

Personally, I use... and I'm probably going to be like crucified for this, but I use a lot of Pepto-Bismol a lot, and I know it's a terrible thing. But I'd say that for most patients, at least in my experience, in my practice, they can handle the sugar-apples pretty well. They don't mind the taste or the color, and it's the cheapest way to get a high amount of bismuth because I tend to dose pretty high. Then, for people that are more sensitive, we'll use different formats and things like that or different products, and then we always talk about it, et cetera. But I'd say for most people, that seems to be a quick and easy way to get that much bismuth in.

Joshua Goldenberg:

So, yeah. But then, interestingly, clinically, people seem to be using stuff across the board. Yeah. So it will be interesting to me. There's also a thought that... and I don't understand the mechanism here, but I've heard this anecdotally, and maybe you can explain it to me. Oh, and then I have a question I want to ask you about the sulfur diet that some forms of it may be more potent than others, right? So you may not need to dose as high if you're using Phase 2 is what I've heard as opposed to just straight-up salicylate versions. So I find that interesting. I don't know if that's true or not. Again, maybe that's something we could piece together, and then... Yeah.

Nirala Jacobi:

Are you talking about the Phase 2 Biofilm Buster?

Joshua Goldenberg:

Yeah, yeah, yeah. Sorry. Yeah.

Nirala Jacobi:

You're talking about the product, right?

Joshua Goldenberg:

Mm-hmm (affirmative). Mm-hmm (affirmative). Yup, yup.

Nirala Jacobi:

Okay. Yeah. Okay.

Joshua Goldenberg:

Yup. So that's the Biofilm designed by Dr. Anderson for Biofilm Disruption. No association with this company, but it has bismuth in it. So the question is... and that's another thing confounding fact.

Nirala Jacobi:

Yeah, that's another thing. Right? What are we treating? Yeah. Are you busting that open? Yeah, and then you're going in with the oregano oil. Yeah.

Joshua Goldenberg:

Yeah, exactly.

Nirala Jacobi:

It's open.

Joshua Goldenberg:

What? How is it working? Is it working? How is it working? Yeah. So I have no idea, right? So that's the idea of the studies. Yeah, so interesting. We tried to tease that apart in the registry to separate if people are trying to bust up biofilms versus go straight bismuth, but I think that's a really interesting question. Yeah. I'd like to know more about it, and then we don't have to answer it now, but I'm curious. Before we get off the air, I've got to... Do you when you do low-sulfur diet because we're at this issue now? We're trying to decide how we define it before we do our literature review. Is there a number? Is there a milligram amount of sulfur that people are like, "Okay. This is consistently what we would call low-sulfur diet," or is it like you just qualitatively tell them, "Go vegan, avoid [crisdofres 00:37:55], and we'll call that low-sulfur?"

Nirala Jacobi:

Yeah, that's what I do. Yeah. I do the latter because it changes for different people in terms of... Some people can handle way more than others, and so typically, what I do is I remove most stuff. I don't even go no-sulfur because I think we need sulfur. It's not like it's a healthy thing to do long-term.

Joshua Goldenberg:

Right.

Nirala Jacobi:

I often tell my patients this is something we are going to go do this for a month, and then we're going to reintroduce foods. Typically, I start with the vegetables again before I go to the meat, and then we work from there, but it's really individualized. Typically, I tell people a month of low sulfur. Some people that are really very responsive to this will react to the... It will be a night and day when they reintroduce the sulfur. So that, to me, is pretty strong evidence. Also, those are the people that respond very well to the bismuth in my experience, and they can tell a huge difference when they used the bismuth. I have people that refuse to get off the bismuth and oregano combo, and I have to reason with them.

Joshua Goldenberg:

Yeah. Yeah.

Nirala Jacobi:

I always tell people, "Look, hydrogen sulfide producers are not the enemy. It's not that it's... These are not typically pathogens that are causing this. It's pathobionts that live there normally. They have overgrown for some reason or another, and it's usually a combination of events that take place for that to occur." So I really, over the last 10 years that I've been focusing exclusively on SIBO, I think I am not as absolute anymore. I know much more now. So it's a bit more individualized, and I use a lot of stool testing and microbe... We have a lab here that looks at actual hydrogen sulfide production by the microbiome, and I find that it's also really helpful. I haven't found one in America that does that. But again, here, we're talking about stool, which is representative of the large intestine, not the small intestine.

Joshua Goldenberg:

Mm-hmm (affirmative). Right, right.

Nirala Jacobi:

So there's still limitations to what we could do there.

Joshua Goldenberg:

Totally. Yeah. Interesting. So a couple of things about that. One is I agree with you completely. I feel like the more I learn, the less I feel like I'm comfortable saying I know. The other is so much of what we do for SIBO is so aggressive, and I... all these antimicrobials and these extreme diets, and I just... Sometimes I just worry so much about upsetting the applecart of a microbiome. You've got this ecosystem trying to find equilibrium, and you want to knock it, but not too much. You want to just knock the right pieces, but not upset the whole applecart. So yeah, I struggle with that, especially with hydrogen sulfide because some of the interventions are a lot stronger. I feel like we have less of a sense of what we're doing.

Joshua Goldenberg:

You brought up a really interesting point with the biofilms, right? Are all biofilms bad? Probably no. There's a natural development in the ecosystem to have these biofilm-like developments, and even if they are bad, a lot of them are stable, right? So you have this stable environment where you're hiding the really scary guys. What happens if you break it open? Right? What does that look like? What does that do?

Joshua Goldenberg:

So, yeah. I don't know where I'm going with this, except to say that SIBO is a fascinating area. When I say SIBO, I also mean like LIBO. It's just a fascinating area to work, and it's exciting because we're at the cutting edge of knowledge of this. We know so little about it formally, but people are suffering. There's so many people with this, and they're suffering, and they need answers. It's not like you can be like, "Well, we're working on the study. I'll call you in two years," or, "Well, RCTs are randomized controlled trials. They're 10 years away, so come back then." It's like people need answers now, and it's this really...

Nirala Jacobi:

Yeah. Mm-hmm (affirmative).

Joshua Goldenberg:

From a clinician perspective and a researcher perspective, it's an awesome place to be, but I totally hear the patient frustration too because it's like, "Wow, you're a clinician that focuses on this, and you don't know what's going on here?" Right? Yeah. It's a mixed bag.

Nirala Jacobi:

I start to shift my thinking in terms of SIBO more to intestinal dysbiosis or imbalances, you know?

Joshua Goldenberg:

Yeah.

Nirala Jacobi:

A lot of people have that. Some people have absolutely true SIBO where their migrating motor complex is just not functioning, and that, to me, is true SIBO, and there are other states. I mean, not to say that the other reasons are not legit in terms of causing SIBO, but there are lots of states where it's just gray area, even though the lactulose breath test is positive, and yes, you have SIBO, but okay, it's at the hundred-minute mark, and it's in the transition zone. What if it's just an imbalance in the normal... It's just a state that has developed due to lots of different reasons, and so I really try to stay or steer away from this. We've got to hunt down all the last little remaining bug that's doing this.

Nirala Jacobi:

It's just I don't think it's doing us any favors because then what? Anyway. So, yeah. Look, you and I could talk for hours. I know this because I think we're very aligned with how we think about the microbiome, and I'm grateful that people like you exist that really into research because I'm not that much. I'm a clinician primarily, and I don't have the brain for it to be honest. So thank you so much. Before we end, let me just ask you about where people can find you both as a practitioner and also, where you are, and yeah, where they can find out more about your work.

Joshua Goldenberg:

Sure. Thank you. Yes. So I wear three major work hats. So one is a teacher. So I teach at AIHM, which is the Academy of Integrative and Holistic Health and Medicine, and so I teach fellows there. So if you're a medical doctoral, or a naturopath, or a chiropractor going and doing a fellowship, I'll teach you how to evaluate research. So you can find me there. I am a researcher at Helfgott, which is part of NUNM, the National University of Natural Medicine. So you can find me there, and then clinically, I see patients one day a week and most... I mean, 99% SIBO. So that's goldenberggicenter.com.

Joshua Goldenberg:

Yeah, those are the main places I am teaching, research, and clinic. I love that diversity. I feel like clinic makes me a better researcher. You're asking clinically-relevant questions, and then yeah. Research makes me a better clinician, right? I think it keeps the clinician hubris in check, right? I love talking to people like you where you've been practicing for so long. You're such an expert in this that you're like, "Yeah, there's so much gray. It's not clear-cut." I get really nervous when people are like, "No, that's not how it's done. That's not what that is." I'm like, "Well, okay. Maybe. I mean, how do you know that?" Right? "Based on your protocol, and what's that based on?" Right? So I love that.

Joshua Goldenberg:

I think medicine is a practice, and we're learning and evolving together. As clinicians, what are the things that's been so beautiful about working in the SIBO space is people like you and Alison. I mean, you've taught us so much. I mean, we will be nowhere. We will be nowhere without you guys, right? You've taught us so much, and there's this spirit of sharing and co-learning I think that happens in this community, and it's just awesome. It's just such an awesome community to be a part of. So I love it, and I love learning together with people and learning from other practitioners as well.

Nirala Jacobi:

Thanks so much. That's very kind of you to say. We've been at it for some time, but I think the more I know... and it's pretty much what you're saying too. The more I know, the more I know that there are so many different influences on this word "SIBO." Right? So that's always the challenge to really individualize our treatment. Dr. Goldenberg, it's been an absolute pleasure to have you on the show. I can't wait for you to come back to talk about the results of this, and what you found, and where to go.

Joshua Goldenberg:

Yes, that will be a fun part two.

Nirala Jacobi:

Yes, that will be really excellent. So thank you so much for your time.

Joshua Goldenberg:

My pleasure. Thank you.