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Chris Mirabile discusses Longevity Breakthroughs with Dr. Ben Weitz.

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Podcast Highlights

1:09  Chris noted that his interest in health started when he was 12 years old when he saw a Men’s Health magazine and got interested in building his body up.  Then he started to feel faint and dizzy and had a seizure and discovered that he had a brain tumor.  He had surgery that saved his life and this fueled his desire to take control of his life and become an entrepreneur and this also planted the seed for his interest in longevity that has blossomed into his current company, NOVOS.

4:19  Chris was in the technology business, but in his personal life he was focused on health and he was into biohacking.  He experimented with nutritional supplements and various sleep, diet, and exercise routines. He was experimenting with measuring various methods of measuring biological outputs.  About 10 years ago he came across a seminal paper in the journal Cell from 2013: The Hallmarks of Aging (López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. doi: 10.1016/j.cell.2013.05.039). This paper was updated in 2023 with 3 additional Hallmarks of Aging: An Expanding Universe. (López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278).

8:18  Chris’s personal diet and lifestyle choices for healthy living include what he calls the longevity diet, which is a modified Mediterranean diet that reduces the intake of wheat and grains and increases the intake of vegetables, mushrooms, and legumes.  He is on the lower end of the carb scale of this longevity diet, though not close to ketogenic. He minimizes his saturate fat intake because he notices when his saturated fat intake goes up, his LDL cholesterol levels go up significantly. He does intermittent fasting, following a 16:8 or even a 19:5.  His eating window is typically between 2 pm and 8 pm.  He admits it would be better if this window were 9 am to 5 pm, since you tend to be more insulin sensitive in the morning, but he has trouble maintaining that, since he is not that hungry when he wakes up. Every so often he does a 24 hour fast.  He starts and ends each day with a 2 mile walk.  Six days a week he will work out for 45 minutes to an hour. Three days he will doing weightlifting and the other 3 days he will do a more intense form of cardio.  Sundays he will rest, though he still might walk or go on an easy bike ride. He notices that after not working out on Sundays, his HRV will pick back up, which he monitors with his Oura ring or his Apple watch. He takes a high quality multivitamin/mineral and uses a salt that is half sodium and half potassium, since most of us do not get enough potassium and this keeps Chris’s blood pressure in a healthy range.

17:58  The Hallmarks of Aging.  The first Hallmark of Aging is mitochondrial dysfunction.  As we age, we have fewer mitochondria per cell, and the mitochondria that we have in each cell are less efficient, which means that we’re able to less efficiently produce the energy, and as a result, our tissues and our organs are not functioning as well as they otherwise would.  A number of ingredients in the NOVOS core product that Chris  developed support mitochondrial health, including magnesium malate, glycine, calcium-alpha-ketoglutarate, fisetin, glucosamine, vitamin C and pterostilbene. 

20:58  Cellular senescence. There are cells in the body that are no longer functioning normally, which are referred to as zombie cells and they secrete something called a SASP (senescence-associated secretory phenotype), which are inflammatory molecules that impact nearby cells and cause them to become senescent as well.  This is one of the reasons why our skin wrinkles as we age. NOVOS core includes fisetin, which is from strawberries, and has been shown to reduce cellular senescence.  NOVOS has conducted an in vitro human cell study that shows that they were able to reduce the footprint of senescent cells by an order of magnitude nearly equal to Rapamycin, which is the gold standard longevity drug.

23:30  Genomic instability.  Another way to understand this is DNA damage and we used to think that simply taking antioxidants would prevent this and some antioxidants can accelerate aging or increase the risk of diseases of aging.  NOVOS core contains pterostilbene, glucosamine, and magnesium malate, which are all good for genomic instability.  Pterostilbene is more effective than resveratrol.  NOVOS is also funding another study that is ongoing that is looking at whether NOVOS core can protect cells from DNA damage from chemo drugs administered to the cells and preliminary results look very promising.

28:10  Proteostasis.  Proteins accumulate inside and outside our cells and they impair the proper functioning of those cells.  One of the ingredients in NOVOS core that favorably impacts proteostasis is micro-dose lithium.  This is completely different than prescription lithium, which is 100 times this dose. This is equivalent to the amount of lithium that is found naturally in some water and fish, which is what we have gotten evolutionarily.  People who live in regions that have higher levels of lithium in the natural water supply have been found to have lower levels of murder, rape, depression, and suicide, and lower rates of neurological disease like Alzheimer’s, dementia, and Parkinson’s. Glycine, glucosamine and fisetin also impact proteostasis.  Glycation could be considered part of proteostasis, though perhaps glycation should be a separate category.

31:34  Altered intracellular communication.  As cells age, communication starts to fall apart and if cells can’t communicate, they’re not going to be able control inflammation and this can also lead to additional senescent cells and dysfunctional stem cells.  Ingredients in NOVOS Core that address this are ginger, fisetin and glucosamine.

33:58  Epigenetic alterations.  Epigenetics refers to turning genes on or off and we want our epigenome to reflect the youngest possible state.  Specific ingredients in NOVOS Core that have been found to have favorable impacts on the epigenome include micro-dose lithium, glycine, calcium-alpha-ketoglutarate, vitamin C (which combines with alpha-ketoglutarate), ginger, and pterostilbene.

39:45  Telomere shortening. Telomeres are the protective end caps of chromosomes, which contain our DNA. Various things can lengthen telomeres including physical exercise and weightlifting.  NOVOS Core contains lithium, magnesium malate, and pterostilbene. each of which have been found to protect the telomeres or possibly even extend telomeres. 

41:12  Deregulated nutrient sensing.  As we age, our bodies and cells become less tuned in to nutrient signals.  Fiseten and pterostilbene that are in NOVOS Core can improve deregulated nutrient sensing. 

42:23  Stem cell exhaustion.  As we age, our stem cells tend to become dysfunctional and die off.  Glycine and alpha-ketoglutarate have been found to improve stem cell health.

                     

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Chris Mirabile is the founder and CEO of Novos, the first nutraceutical company that targets the 12 biological causes of aging to increase longevity. Chris has achieved a biological age that’s 13.6 years younger than his chronological age according to the epigenetic test DunedInPACE, and he continues to age at a rate that’s 31% slower than normal.  His website is NovosLabs.com.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure.  Dr. Weitz has also successfully helped many patients with managing their weight and improving their athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

 

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Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting-edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast.

                                Hello, Rational Wellness podcasters. Our topic for today is why we age and what we can do about it with Chris Mirabile. Chris Mirabile is the founder and CEO of NOVOS, the first nutraceutical company that targets the 12 biological causes of aging to increase longevity. Chris personally has achieved a biological age that’s 13.6 years younger than his chronological age according to the epigenetic test DunedinPACE, and he continues to age at a rate that’s 31% slower than normal.  Chris, thank you so much for joining us today.

Chris:                   Thank you for having me, Ben.

Dr. Weitz:            Great. So, can you tell us about your personal story and health challenge you had to deal with as a child?

Chris:                   Sure. Well, I started getting interested in health when I was 12 years old. I was at the bookstore and I saw a Men’s Health magazine, and I was inspired by-

Dr. Weitz:            Like Muscle & Fitness or one of those?

Chris:                   Muscle & Fitness, Men’s Health, Muscle Media magazine, all of them. There was a whole bunch back then. And yeah, I picked them up and I was inspired by the guys in the magazine and I wanted to be in good shape. Admittedly, it was purely superficial. I wanted to be attractive to the girls in elementary school. I was only 12. But I set up a pull-up bar in my basement with my father, and every day after school, I’d come home and do my pushups, my pull-ups, and then eventually started weightlifting.  But then, I was suddenly stopped in my tracks when I was 16 years old. I was in New York City for a school trip, and I suddenly started to feel faint and dizzy, and next thing I knew, I woke up with blood all over my shirt. I had severed my tongue from a seizure that was caused by a brain tumor that was growing in my left temporal lobe above my ear unexpectedly. It was more than a golf ball size, and they had to do emergency surgery within just a few days.  That took me from being very physically active to laying in bed in a hospital bed, contemplating more mortality and the possibility that I wouldn’t wake up after my surgery and all of the things I had yet to experience in life. And so, I started to think if I make it through this, I want to take control of my life and there’s so many things I’d like to do. And that’s part of what motivated me to be an entrepreneur but also planted the seed for my interest in longevity that has blossomed into my company now NOVOS.

Dr. Weitz:            Right. So, you went to college actually for business. How did you come around to being involved in a nutraceutical business?

Chris:                   Yeah, so I studied at NYU Stern. I majored in finance, economics and international business largely because I knew I wanted to be an entrepreneur, and I wanted to understand business and entrepreneurship and especially the financial side of a business. My first year out of college, I went into private equity, more on the banking side, worked on Park Avenue. Although the money was great, it didn’t speak to me. And so, within one year of starting that career, I quit and I started a social network that won NYU’s Business Plan Competition.  And that was enough to get me to leave that job and to start that entrepreneurial journey, which was far more difficult and challenging than most would expect when they hear the stories of the massive successes in entrepreneurship. But nonetheless, I was in technology and in my personal life, I was really focused on health. I experimented with the biohacking side of health with different types of supplements and sleep routines and diet routines and exercise routines and so on, and did a lot of quantified self where I was measuring different biological outputs.

                                And based on that, making more informed decisions than I otherwise would have if I didn’t have those tools. And all the while I was asking myself the question, “Are the things that I’m doing for these short-term goals?” And those short-term goals may have been to run a faster mile or to do more pull-ups in 60 seconds or to lift a heavier deadlift. They may have also been to focus better at work or to be able to work longer, be in a better mood, things like that. My question was always, “Are the approaches I’m taking good, bad, or neutral for me in the long-term?”  And oftentimes there was no obvious answer. If you follow a specific diet or you take a specific supplement, knowing what the repercussions of that will be in 10, 20, 40, 50 years, it’s not always clear. What I didn’t realize at the time was I was dealing with a concept at least on a genetic basis known as antagonistic pleiotropy, which is the overly simplified form of that would essentially be what’s good for you today can come back to harm you tomorrow. And so, I wanted to make sure that I wasn’t harming myself tomorrow because of the experience I had with the brain tumor, and the last thing I wanted was to be laying in a hospital bed again, possibly dying. So, that was something I started to look into.

                                And about almost 10 years ago now, I came across a seminal paper in a prestigious journal known as Cell called The Hallmarks of Aging. It’s a very popular paper, and that was the moment of epiphany for me. That was the aha moment when I realized, “Wow, we actually do understand the biological causes of aging, and if I look through that lens, I can start to answer that question of is this good for me in the short-term and in the long-term as well.” And that started my journey in the longevity space.

Dr. Weitz:            Yeah, I read that paper. I noticed that it had nine factors of aging, and there’s a 2023 version that now has 12 causes.

Chris:                   Yes, that’s right. So, just a few months ago, the same authors of that original paper published the new one that identified three additional hallmarks. Though anyone in the longevity space could tell you, “We saw this coming.” There was enough evidence and studies and presentations in the biomedical field where everyone knew that, for example, inflammaging was going to come up as another hallmark of aging, this chronic low-grade inflammation that takes place as part of aging.

Dr. Weitz:            And the microbiome, that’s one of the ones that was added as well.

Chris:                   Exactly, right. And we all know about the gut-brain connection, but few people know that there’s many other axes for the gut, like the gut-liver axis and the gut-kidney axis.

Dr. Weitz:            Gut-heart axis.

Chris:                   Yes.

Dr. Weitz:            In the functional medicine world, which I thrive in, is we’re always looking at the gut as a major factor in almost every issue we’re dealing with.

Chris:                   Definitely. It all, or I shouldn’t say all, but much starts in the gut. It begins there for many people in many conditions.

Dr. Weitz:            Maybe you can tell us about your personal diet, exercise, lifestyle program that’s enabled you to reverse your aging.

Chris:                   Sure, sure. Let’s see. I’ll think of this in terms of maybe diet first. When it comes to diet-

Dr. Weitz:            I noticed on your website you talk about the longevity diet.

Chris:                   Yes, yes. At NOVOS, we’ve put together something known as the NOVOS Longevity Diet, which is based on the foundation of the Mediterranean diet. The Mediterranean diet has been found in study after study to be the best diet for longevity, the most conducive to long lifespan, a long health span, reduction in risk of heart disease and cancer and diabetes and so on. Also, the best neurological outcomes, lowest rates of depression and so on. But what we’ve done is we’ve taken some less than ideal aspects of that.  For example, higher intakes of, say, wheat products and grains and modified it somewhat to increase, for example, the intake of vegetables, mushrooms, legumes, to reduce the amount of those starchy lower nutrient-rich foods for more nutrient-rich foods with less starch. So, to that point, I essentially follow that type of diet. I’m a little bit on the lower end of the carb scale than I would necessarily like to be, to be honest.  I find myself constantly going on the lower end of the spectrum, but I do find myself being more energized and in a better mood when I add more carbs into my diet probably because of the increases in serotonin that come from it. By extension, it increases in melatonin and better sleep I experience when I have a little bit more carb. But generally speaking, for the general population, I am much lower on the carb spectrum, but definitely not close to ketogenic.

                                Generally speaking, I minimize my saturated fat intake. Now I’m not afraid of saturated fats but I choose them carefully, which ones I take in, because I do notice that the higher saturated fat intake I have, my cholesterol LDL levels go up significantly. So, I want to reduce those LDL levels as much as I can. I intermittent fast, so I typically follow 16/8 or 19/5, something in that range. So, basically, 2:00 p.m. to 7:00 or 8:00 p.m. is my eating window.  Now, ideally, that would actually be earlier. It would be better if I did like 9:00 a.m. to 5:00 p.m. but I have trouble maintaining that. I’m not that hungry when I wake up. And I also find myself not sleeping as well when I go that long before waking up without food. So, it shifted a little bit later, but ideally, you’re more insulin sensitive in the morning. Some studies have found it’s better to actually start eating earlier in the day and ending earlier. Every so often I’ll do a 24-hour fast. So, once every couple of weeks, I’ll go maybe Thursday dinner to Friday dinner without eating.

                                My exercise routine is every day, I bookend my days with walking. So, I’ll start my day with about a two-mile walk. I’ll end my day with approximately a two-hour walk. In both cases, I’m typically still being productive. As an entrepreneur, I’m always doing something whether that be on the work call or responding to emails or something or listening to a podcast. And then, in the mornings, I’ll exercise six out of seven days of the week. So, three of those days are weightlifting, 45 minutes to an hour, and the other three days are a more intense form of cardio for, again, 45 minutes to an hour.

                                And then, Sundays are my rest days where I’m still walking a lot. I might go on an easy bike ride, so I’m still physically active, but I’m not pushing myself. I’m not pushing my body. And when I look at my biometrics through the Oura Ring or the Apple Watch, my HRV really picks back up again from that lighter load. I supplement with a high-quality multivitamins, multi-minerals. I make sure I get adequate potassium in my diet, not only through the foods I eat, but I also use a Lite Salt, which is half sodium, half potassium salt.  Most people are deficient in potassium even when eating a healthy diet. And this is my way to increase those levels of potassium. My blood pressure is in a very healthy range I believe as a result of that.

Dr. Weitz:            What product are you taking for the potassium salt?

Chris:                   There’s a few out there. There’s some that are 100% potassium salt. They don’t taste very good. Morton’s brand, very common brand. They make a 50/50 mix of potassium sodium, literally called Lite Salt, L-I-T-E. Another way you can do it is you can buy the pure potassium salt, and then if you wanted to stick with something like pink Himalayan salt, some natural salt with other minerals in it, you do 50/50 and you do your own mix basically.

Dr. Weitz:            That’s a cool idea.

Chris:                   Yeah, it’s a great way to get up into the multiple grams of potassium. If you look at, historically speaking-

Dr. Weitz:            People take 99 milligram potassium capsule and it’s insignificant. Yeah.

Chris:                   It does practically nothing. So, if you’re able to add two, three grams of potassium to your diet per day, of course, making sure you’re getting adequate sodium. It actually really offsets a lot of the negative sides of sodium. People are oftentimes afraid of sodium and they say, “I have a sodium-free diet.” What I would say to that is, if you’re physically active or you’re out sweating, that’s actually not a good idea. You need the sodium. There’s a reason why the ancient Romans were paid in salt, the Roman warriors. They’re paid in salt because when you’re sweating, you need it.

                                So, I would just say, get that salt in your diet but then offset it with potassium. We have our cells have the sodium-potassium pump. You don’t want to be deficient in either one of those. It affects us neurologically. It affects all of our organs. It affects our muscles as well. That’s on the diet side. What I do, I mentioned exercise. When it comes to weightlifting, I do a combination of a little bit of powerlifting, a lot of strength lifting, sometimes high rep. I like to have a nice balance.

                                Same thing when it comes to cardio. I like to be very fast to sprint, but I also like to be able to run six, seven miles without a problem. So, I’ll mix things up. Maybe I’ll go out for a five-mile run, but for two of those miles I’ll do high-intensity sprints, and then I’ll jog the remainder. I’m always shocking my body and doing things a little bit different for each of the workouts. What else? Sleep is very important to me. I’m very regimented with my sleep. I make sure that I’m getting to bed typically within between 10:30 and 11:00 p.m. work nights.

                                And then, on weekends, I might extend that to midnight or something, but generally speaking, maybe 11:30. So, within an hour, I wake up, I get sunlight in my eyes right away. I go out for a walk, have some coffee, actually after my morning workout. So, it’s a couple of hours into the day. It’s a black coffee. What else? When I sleep, I wear earplugs. I wear sleep mask. So, this way when my girlfriend is waking up and she’s doing things, she’s not waking me up. And that really improves the quality of my sleep, which I’ve tracked and see that it’s significantly better that way.

                                Generally speaking, despite stressors that might enter my life whether personal, or as an entrepreneur as you can imagine almost every day there’s some stressor, just really being mindful. I practiced meditation for more than a decade now. I don’t need to do it as frequently as I have before because I think I’ve gotten myself to a different set point. But sometimes when there’s a lot of stress, I will just sit still and just focus on my breathing, and that goes a very long way for me.  Those are the main things I think of. And, oh, I was talking about supplements before.

Dr. Weitz:            Supplements. That’s right. Yeah.

Chris:                   So, the general health, multivitamins, multi-minerals, fish oil, and then of course longevity supplements, which my company produces. Fortunately, I’m able to take the equivalent of 13 different supplements by just having a sachet drink mix and two pills. So, really simplifying that more complex routine and making it into something that’s a daily habit as part of my lunch.

Dr. Weitz:            Cool. Let’s talk about the causes of aging, these hallmarks of aging, and then maybe we can work in some of the supplements that can be beneficial in moving the needle on these.

Chris:                   Sure. Happy to. I’ll start with the original nine that we talked about before from the paper, The Hallmarks of Aging. The first is one that your audience is probably very familiar with is one of the most popular ones. It’s mitochondrial dysfunction. So, our mitochondria being the power plants of our cells, they enable us to move, to think, for our organs to function, and they’re taking the carbs, the fat, and sometimes even the protein that we’re ingesting, and then converting that into energy in the form of ATP.  And as we age, we have fewer mitochondria per cell, and the mitochondria that we have in each cell is less efficient. So, we’re able to less efficiently produce the energy, and as a result, our tissues and our organs by extension are not functioning as well as they otherwise would. And there are ingredients in NOVOS’s foundational supplement, NOVOS Core, that positively impact mitochondrial health.  That’s everything from malate, which is contained within the magnesium malate, glycine, calcium-alpha-ketoglutarate, fisetin, glucosamine, vitamin C and pterostilbene. The second hallmark is cellular senescence.

Dr. Weitz:            Why did you choose malate? Because when we talk about mitochondria, some of the supplements that tend to come up the quickest are things like alpha-lipoic acid, NAC, CoQ10, L-carnitine.

Chris:                     Yeah. Well, so not only is malate part of the Krebs cycle and it’s found to increase or improve healthy energy levels in humans. There’s studies that find that improves energy levels in humans. It’s also a substance that’s been found to extend lifespan in multiple organisms. In fact, every single ingredient that we use, we run it through this filter of multiple different requirements, which you can find. If you go to novoslabs.com/approach, you can see what those requirements are.  One of those requirements is that it’s been shown to extend lifespan in at least one species, ideally multiple species, because if it’s found to do so in multiple species, that hints at the biological mechanism being evolutionarily conserved. In other words, evolution has decided that this is important enough to conserve it, and therefore it’s most likely going to be in us humans as well who are harder to test for lifespan because of how long we live.

Dr. Weitz:            Right. Okay.

Chris:                   Make sense?

Dr. Weitz:            Yes.

Chris:                   Okay, great. So, the second one is cellular senescence. This is what a lot of people refer to as zombie cells. These are cells that are not living nor dead. Sometimes the body produces these, for example, to arrest a cancer. It’s not the only reason but that is one of the reasons. And they fly under the radar of our immune systems. The immune system should theoretically identify these and remove these cells or through autophagy, digest the components and then recycle these components. But for one reason or another, they aren’t. And the problem with them is they secrete something called a SASP.  And the SASP is senescence-associated secretory phenotype. It’s essentially a fancy way of saying it secretes inflammatory molecules that then impact nearby cells and cause them to become senescent as well. So, it becomes an exponential process as we age, is one of the reasons why our skin wrinkles, for example. And to reduce cellular senescence, there’s one key ingredient in NOVOS core. It’s called fisetin. Fisetin is found in strawberries and it has been shown to have favorable effects on senescent cells, reducing cellular senescence.

                                Now with that said, we’ve done an in vitro human cell study at University of Newcastle in the United Kingdom where we were able to show that we reduced the footprint of senescent cells by an order of magnitude nearly equal to the prescription drug rapamycin. And rapamycin is the gold-standard longevity drug. It is what everything is compared to, and the fact that we were practically equal to this prescription drug was really exciting for us for this specific dimension of cellular senescence.

Dr. Weitz:            Especially since there’s all these problems around potentially taking rapamycin because it suppresses the immune system and people are trying to figure out ways where you can just take it once or twice a week to try to decrease the negative effects while still getting the positive effects. Somebody like myself, I’ve decided so far not to consider taking rapamycin. So, the idea that we could take a nutritional supplement that doesn’t have any of those negative effects is very exciting and very impressive that your nutraceutical company is able to fund research.

Chris:                     Yeah, thank you. That’s not the only thing. So, maybe I’ll skip ahead to another hallmark of aging that we have found that we’ve done research related to and found benefits for. So, that’s genomic instability. Another way to put that is DNA damage. And this used to be what many scientists thought was the reason we age, DNA damage. And therefore antioxidants would be the way that we slow down or stop aging. And research has been disappointing on that front in the sense that antioxidants don’t stop or slow down aging. In fact, many antioxidants can even accelerate aging or increase the risk of diseases of aging specifically.  But with that said, DNA damage is a factor. It is a contributor to aging. It’s just that there’s 11 others, right? It’s not the ultimate answer. Now, when it comes to DNA damage, something we want to reduce as much as we possibly can, NOVOS, we’ve done multiple in vitro human studies, one in which we irradiated human cells and one set of cells had NOVOS administered. Another set of cells did not. It was the control. It was found that we reduced oxidative damage to the DNA by more than 70%, which the lab that ran the study had done more than $6 or $7 million worth of the same study with different natural and prescription drugs and found nothing compared to the results that we were getting.

                                They were shocked by the result. They even called their CEO to tell them the results that we got from our study. There’s another study that we have not yet published that’s currently ongoing, but what I can say about it is it’s being done at a university in Italy. And they are administering chemotherapeutics to human skin cells. And the chemo that they use, they’re using two different ones. One is moderately intense, the other is extremely intense. The extremely intense one, it doesn’t simply cause oxidative damage to the DNA. It actually causes single and double-strand breaks.  The analogy I like to give is oxidative damage would be like a car rusting. Strand breaks are like a chopping the car in half at the axle like you’re completely demolishing that car, right? And what was found was that with this intense chemo, practically 100% of the DNA was either single or double-strand breaks. After administering the NOVOS formulation, there was, I can’t say specifically what number, but a significant number of DNA that did not have any strand breaks whatsoever.  That again, is very promising, the effect that we can have to protect the DNA.

Dr. Weitz:            Right. That’s very cool. Do we have reasonable ways to measure DNA damage in humans?

Chris:                   Within the human in vivo sense-

Dr. Weitz:            I guess maybe we have telomere length, right? That’s probably the best.

Chris:                   Telomere length would be an offshoot of that in the sense that your telomeres are going to shorten more when there’s more DNA damage because you need to then replicate the cells that much more frequently and so on. But it’s not a direct measurement of the DNA damage per se. I would imagine just getting a biopsy of the cells and then looking specifically at the DNA before and after, you could probably do it, but I’m not aware of many studies that take that approach. It’s oftentimes in vitro and looking at the loci and seeing how many loci there are is typically the marker that they use for the DNA damage.

Dr. Weitz:            Yeah, it’s interesting. It’s too bad we don’t have ways to measure a lot of these hallmarks of aging commercially available for people. Like measuring mitochondrial dysfunction is not an easy thing to do either, measuring senescent cells is… it’d be cool to have some lab tests that could measure these.

Chris:                     Yeah, that would be ideal. And I’m sure that they’re coming down the pipeline. I’m sure there are people out there thinking about offering these types of tests but not easily available.

Dr. Weitz:            Sorry for running down a rabbit hole. In your product, do you reduce genomic damage? What are some of the ingredients that you have to do that?

Chris:                     Pterostilbene which is the much more effective and better studied equivalence to resveratrol. Resveratrol is a popularized ingredient that has been shown by many researchers to not really do what… it hasn’t lived up to the promise, I’ll put it that way. Whereas pterostilbene is a close relative to that molecule. It contains three methyl groups, which is very good for methylation and the epigenome and NAD production, which we may talk about as well in regards to this molecule called NMN, which is in our NOVOS Boost formula. It contains pterostilbene, glucosamine, and magnesium malate are all good for genomic instability.

                                The next hallmark is loss of proteostasis. Over time, more and more proteins, they accumulate inside of our cells and outside of our cells. And by this happening, it impairs the proper functioning of those cells. Imagine having a lot of garbage inside of your house and outside of your house, it’s going to be harder for you to get indoors. It’s going to be harder for you to access the kitchen and the bathroom. Your home becomes somewhat dysfunctional. The same thing happens with our cells. Our bodies should be removing that protein, but because of a loss of proteostasis as we age, it becomes more difficult.  And ingredients in NOVOS Core that favorably impact loss of proteostasis are micro-dose lithium. Lithium is this ingredient that raises a lot of eyebrows. A lot of people think of their cell phones and lithium-ion batteries and so on. Or they think of psychiatric patients who take prescription doses of lithium, which is far higher dose. Prescription doses are 100x the dose of a micro-dose. A micro-dose is equivalent to what we have gotten evolutionarily. Lithium is found in natural water supply. It’s found in wild fish and so on. And we’ve had it throughout evolution.

                                In fact, New York Times did a story on this maybe probably almost a decade ago now, where they looked at people living in regions that had higher levels of lithium in the natural water supply, and they found lower levels of murder, of rape, of depression, of suicide, lower rates of Alzheimer’s, dementia, Parkinson’s. It’s basically something that has a very favorable impact on the brain, on human psychology and neurology. It also has a favorable impact on the epigenome. It’s one of the more powerful ingredients in the formulation.

                                There’s also glycine, which is an amino acid found in collagen we’re deficient in our diets nowadays, glucosamine and fisetin. Next is altered intracellular communication. Cells need to… Cells are part of this vast network. And as we age, the communication starts to fall apart. Part of the reason for it is because of that loss of proteostasis. Imagine if you have proteins blocking the receptor sites on a cell is going to be that much harder for cells to be able to secrete molecules that are then received properly.

                            So, if the cells can’t communicate with each other that well, they’re not going to be able to set in motion the processes that should be taking place. This comes as a result of hostile environments with inflammation and so on, and they could then lead to additional inflammation. They can lead to additional senescent cells, dysfunctional stem cells and so on. And ingredients in NOVOS Core that address this are ginger, fisetin and glucosamine. We went over genomic instability. So, next is epigenetic alterations.

Dr. Weitz:            Let me just ask you one question.

Chris:                   Sure.

Dr. Weitz:            On the proteostasis, is glycated proteins, proteins damaged from sugar, is that part of that proteostasis concept?

Chris:                   Yes, it is. In fact, before the 12 hallmarks of aging were introduced this year, we actually suggested that there was a 10th hallmark when there were only nine, that being glycation. So, technically, you could say it’s part of proteostasis, but just like autophagy was just added when it could also be considered somewhat related to proteostasis, we felt like glycation deserved almost a category of its own. And perhaps one day there will be, and it will be 13 hallmarks or 14 hallmarks. But glycation, they’re all interconnected. As I think people are realizing as I talk through them, they all cause each other in one way or another.  And that’s why it becomes exponential because as one starts to pick up, it accelerates the other, which accelerates the first one again and so on. And they all are either working together or against each other. And unfortunately, as part of aging, they’re working against each other.

Dr. Weitz:            Right. Okay.

Chris:                   Let’s see. So, next is epigenetic alterations. The epigenome is, epi being layer on top of your genome. It is essentially which genes are turned on or off. So, if you think of your genome as being the piano keys, this is something permanent. It’s something that’s set in place from your birth. Your epigenome are which of those keys are being played. And so, when you’re young, it might be playing a beautiful song. It might be Tchaikovsky. But as you age, certain keys are misplaced or not played when they should be. You don’t have the rhythm anymore. And these patterns start to emerge.  And that’s how epigenetic clocks and biological age clocks function is by looking at specific genes, whether they’re turned on or off or to what degree, because it’s more like a dimmer switch. And then, they can find these patterns and then determine how old you are biologically by comparing you to everyone else out there. Now, certain genes are turning on that shouldn’t turn on. These might be genes that are inflammatory or cells might start to identify as the wrong cell. Your skin might think it’s a hair follicle or something, and then suddenly hair starts to appear where it shouldn’t and vice versa.

                                So, a gene that should be on like an anti-inflammatory gene might turn off. And so, we want our epigenome to reflect the youngest state possible. And there are specific ingredients in NOVOS Core that have been found to have favorable impacts on the epigenome. And that would be, again, micro-dose lithium, glycine, calcium-alpha-ketoglutarate, vitamin C, in particular the way that it combines with alpha-ketoglutarate, it basically enhances the effect of the alpha-ketoglutarate. Ginger and pterostilbene.

Dr. Weitz:            I just want to stop you for a second, sorry.

Chris:                     Sure.

Dr. Weitz:            I was reading on your website about the alpha-ketoglutarate and I’ve been using alpha-ketoglutarate. And you make a point out of the fact that calcium-alpha-ketoglutarate is more effective than just alpha-ketoglutarate, which is I don’t think the calcium-alpha-glutarate is readily available. And I also notice that in your product, you have 1100 milligrams of the calcium-alpha-ketoglutarate. And most of the alpha-ketoglutarate supplements that we’ve been carrying have 300 milligrams in a capsule.

Chris:                     Thanks for raising those points. So, a couple of things to point out. One is that the calcium form of alpha-ketoglutarate is most conducive to improving lifespan, partially mediated through the absorption time, the amount of time it takes for the body to break it down. So, it’s a little bit more of a continuous dose of the AKG. Calcium, also, a lot of people, especially health-minded people aren’t consuming as much dairy or milk. A lot of people are becoming deficient in calcium, so it’s good to have a little bit of added calcium. And then, in terms of the dosage, that brings up a more broad concept, which is the dosage across the NOVOS Core product.

                                We have nearly 7 grams of active longevity ingredients in our formulation. So, think about that 7000 milligrams of actives, whereas most supplements that are $50, $100 are only giving you 500 milligrams or a gram or 2 grams of actives. We’re well above that. And our price point is between $79 to $109 per month, depending on whether you subscribe or you do a one-time purchase. So, dollar per gram. We are amongst the most affordable products out there, and we’re definitely the most powerful out there as well.

Dr. Weitz:            Is your product available for practitioners to set up a wholesale account?

Chris:                   It’s funny you asked that because yes, we just begun that process of bringing on wholesalers. So, we’re talking with a number of medical clinicians who are interested in offering NOVOS Core, NOVOS Boost, which is our NMN product, and NOVOS Age, which is our biological age test kit, which includes the DunedinPACE clock for your pace of aging, a biological age clock, which is not as accurate as DunedinPACE, but people want to scratch that itch so we include it. And then, telomere length, and we will tell you your percentile according to your chronological age for your telomere length.  And we also then include in the results, the report you received a lot of advice and guidance for how to improve your scores.

Dr. Weitz:            Okay, cool. And so, practitioners listening, where would they go to find out about that?

Chris:                   If they go to novoslabs.com and they scroll to the bottom of the website, they’ll see a Contact Us link. They’ll see a section specifically for either affiliate, or there’s no purchase required. They just get a hyperlink, and then they’ll get a commission for sales. Or they’ll find the wholesale form where they would be purchasing in bulk and getting a substantial discount.

Dr. Weitz:            Okay, cool. Okay, go ahead.

Chris:                   All right. I think we’ve gone through seven or so of them so far. Telomere shortening is something that we’ve already begun to discuss. The idea of telomeres are, these are the protective end caps of chromosomes. And chromosomes are what contain our DNA. And so, they’re essentially protecting our DNA. Every time a cell divides and we’re producing replicas of the DNA, the telomeres get shorter. By extension, you would expect that someone who is older, who has had more cellular divisions, or someone who has had a lot of DNA damage, they’re going to have shorter telomeres.

                                Now, with that said, there are different things you can do that can actually lengthen telomeres. For example, certain diets, certain supplements, even like physical exercise and weightlifting. I believe there’s a study that found weightlifting can extend telomere length. So, if you find you have shorter telomeres, for example, maybe you purchase the NOVOS Age test and you see that you’re in the 40th percentile, hope is not lost. You can improve that and actually raise your percentile.

                                And within NOVOS Core, we have lithium, magnesium malate, and pterostilbene each of which have been found to protect the telomeres or possibly even extend telomeres. I believe number eight or nine, I think eight at this point is deregulated nutrient sensing. So, as we age, our bodies and our cells become less tuned to nutrient signals. What are nutrient signals? It’s, for example, having sugar in our blood glucose, right? It is having insulin in our blood, the fatty acids in our blood.

                                Our bodies should be tuned to these to know that, for example, if your blood glucose is at 120 release insulin to lower that below 100. But as we age, our bodies are less tuned to this, and therefore our blood glucose might start to creep up. It might require more insulin to be able to shuttle that glucose to the cells because we’re becoming insulin-insensitive. And so, this is something that can then lead to metabolic disorders. We see it manifest in the form of additional body fat and so on. And so, ingredients like fisetin and pterostilbene can improve the deregulated nutrient sensing.

                                Number nine is something that your listeners are probably very aware of, which is stem cell exhaustion. Our stem cells are essentially making replicas of themselves to create new cells. And as we age, they either become dysfunctional or they die off. So, we have fewer stem cells and those that we have are not capable of reducing perfect replicas anymore. And so, we want to be able to keep them healthy, keep as many of them around as possible, even have copies of stem cells. Stem cells can copy themselves. So, have copies of stem cells produced and ingredients like glycine and alpha-ketoglutarate have been found to improve stem cell health.

                                The three new ones, we’re on the final stretch here. One is inflammaging, which we referenced earlier. So, this is the chronic low-grade inflammation that starts to pick up as we age. When we’re in our 30s, it’s this mild hum. You might not even hear it. And when you’re in your 40s, you start to hear it, becomes audible. And then, in your 50s and 60s and beyond, it starts to really be present. And so, the question is how can we reduce that chronic inflammation? Because as we all know, inflammation is the root cause of so many different illnesses. Sometimes it’s an acute inflammatory environment.

                                For example, a workout causes acute inflammation, but that’s a healthy inflammation that the body through the process known as hormesis comes back stronger from that workout. Or there might be inflammation from cutting your skin. There’s some inflammation localized to that area, that’s fine. The immune system takes care of that and repairs. But when you have this systemic body wide, low-grade inflammation that starts to wear on our bodies over time.

                                And many ingredients in NOVOS Core have been found to reduce the inflammatory environment. So, that’s everything from glycine to fisetin, pterostilbene, ginger, the micro-dose lithium, magnesium malate, alpha-ketoglutarate, Rhodiola. And then, in NOVOS Boost, the NMN has also been found to reduce inflammaging.

Dr. Weitz:            I’m surprised you didn’t include curcumin in your product, which is one of my favorite herbs and very powerful anti-inflammatory.

Chris:                   Yeah. There are specific ingredients that show a lot of promise but that we intentionally didn’t include. And every ingredient has a different reason why we didn’t include it. If you go to novoslabs.com and you click on the little search button on the top-right corner, and you search for something to the effect of ingredients not included, you’ll find that article. And it’s got a couple of dozen different ingredients that we consider. Quercetin was another one for the senolytic activity. We decided not to, partly because of our consultation with one of our scientific advisory board members. We have six scientific advisory board members from Harvard, MIT, and the Salk Institute.

                                This one is from the Salk Institute, Dr. Pamela Maher. And she studies quercetin and fisetin and other similar molecules. And she was concerned about the possibility of damaging healthy cells from quercetin, from chronic intake of quercetin. Whereas fisetin seems to be more powerful for the senolytic activity while meanwhile also having a lower side effect profile essentially. So, next is disabled autophagy. We talked about autophagy or we referenced it earlier. That’s the idea of our bodies, our immune systems taking cells and their components and recycling them.

                                Imagine an old cell, it’s starting to break down. It’s not functioning properly. The immune system can identify this and basically digest it and then use the proteins and lipids from that and recycle it for new cells, for example. And ingredients in NOVOS that help in with this process are micro-dose lithium, glucosamine, acetyl glucosamine, which is a distinct ingredient from glucosamine. And acetyl glucosamine is contained within hyaluronic acid. We included hyaluronic acid in our formula specifically for the acetyl glucosamine. But a nice added bonus is that hyaluronic acid orally ingested actually improves skin health.

                                It improves skin moisture, joint health as well. It helps to lubricate the joints. So, there’s multiple benefits from that hyaluronic acid, but we really wanted it for the acetyl glucosamine. Finally, there’s dysbiosis. So, this is the microbiome that we mentioned earlier. And so, as we age, the composition of our microbiome, the different bacterial species that we have within it, even fungal species and so on, it changes. And there are certain types of bacteria that start to proliferate that can lead to, for example, inflammation and not the ideal environment.

                                And when we look at some of the longest-lived people, the centenarians and the supercentenarians, we find that they have a distinct microbiome compared to the average person who’s dying much earlier. For example, they have higher levels of a specific bacteria known as akkermansia. There are different ingredients that have been found to have a favorable impact on the microbiome. And within NOVOS Core, those include ginger, pterostilbene, fisetin, rhodiola, and the micro-dose lithium.

                                That was all 12 of the hallmarks of aging that scientists have identified to this point. And as I hope you can see, we have multiple ingredients that impact each of these hallmarks of aging. So, it’s a combinatorial synergistic approach that we’re taking, being mindful of also not having any dissynergies, which are essentially negative synergies that can also take place when you combine ingredients. These are things we were careful to avoid while formulating the product.

Dr. Weitz:            And then, you have your Boost product, which is NMN.

Chris:                     Correct. Yeah, NMN, nicotinamide mononucleotide, is a precursor, a direct precursor to the molecule NAD plus. NAD plus is involved in energy production. It’s involved in the production of sirtuins, which are enzymes or proteins that repair our DNA. They help to maintain the epigenome. So, there’s a lot of vital processes that come from NAD plus in the Krebs cycle. And as we age, we have less NAD plus, we have less NMN. And there are many studies finding in animals, as well as in humans that NMN can improve health span and energy production. Some people even report anecdotally online that it reduces gray hair. A lot of different benefits people are experiencing from it.

Dr. Weitz:            Why did you decide to go with the NMN as opposed to NR?

Chris:                   A few reasons. One is if you think about NR, it’s actually a precursor to NMN. And so, you have to convert the NR to NMN and the NMN to the NAD. The question for a while was, is NMN actually absorbed through the gut? And we got the answer. Yes, it is absorbed through the gut, so you don’t need the NR. We wrote an article about this. This is actually one of the more popular articles on our website. If you search for NMN versus NR, we talk through that, and I think there’s close to two dozen different points that we raised for why we chose NMN over the NR.  But essentially we feel that it’s more effective and NR is, it’s difficult to absorb through the gut. The liver converts a lot of it, and ultimately, we think that you get more bang for your buck with the NMN.

Dr. Weitz:            Interesting. Yeah. It seems to be not that easily available as it-

Chris:                   NMN.

Dr. Weitz:            Yeah, NMN. Yeah.

Chris:                   Yes. Well, there’s this ongoing issue where there’s a question of whether it is going to be restricted to prescription sell only or over the counter. And this is an FDA-level issue. It’s not yet determined. So, we’ve been advised to continue selling it. Ultimately, it’s a natural substance. It’s found in human biology. It’s also found in food like tomatoes and so on. And so, the question really comes down to whether there’s any reason to restrict consumers from being able to purchase something that is found in the foods we eat and in our bodies to prescription-only use.  And it really comes down to a loophole that one company is trying to exploit to get exclusive rights to it but that is far from definitive at this point, and many companies in the industry are fighting that. In fact, I’ll be meeting with members of Congress next month to discuss the issue specifically.

Dr. Weitz:            Interesting. One company is trying to make it a prescription drug, yeah?

Chris:                   Yes. And one very well-known scientist is on the board of that company. The company is called MetroBiotech, but I won’t throw any mud. I won’t name names, but there is someone well-known in the longevity space who’s on that board.

Dr. Weitz:            Yeah, I think I know who you’re talking about. Well, that’s interesting. Okay. Awesome discussion. Final thoughts for our listeners and viewers?

Chris:                   Sure. Well, I would say that when it comes to longevity, there’s no magic pill. And NOVOS despite the fact that we create formulations, I would not try to sell you on the idea that there is a single magic pill that’s going to extend your lifespan, and you can neglect these other aspects of your life. There’s all of these components that come together, everything from diet to activity to stress reduction, rest and recovery, in particular sleep, making sure that you’re not deficient in any critical required nutrients. These are the vitamins and minerals that there are RDA is set for. And it’s nearly impossible to get an adequate dosage through diet alone.

                                And then, there’s longevity supplements as well, which are shown to improve health span and lifespan. So, it’s all part of this bigger picture. And NOVOS as a company, we’re public benefit corporation, so my intention is to improve human health whether people are customers of ours or not. Of course, we hope people will sign on to our platform and purchase our products because we really do truly believe in them and we’re proving them out with science. But if not, we still want to improve people’s health spans and lifespans. So, we provide a lot of free resources on our website.

                                We’ve got almost 150 articles on our website written by MDs and PhDs, scientifically referenced. We offer free tools. For example, we just launched last week this longevity assessment that you can fill out. It’s a questionnaire, and then we give you recommendations for what is most important for you to focus on. So, those are the red, recommendations, yellow for moderately important, and then green, these are the things you’re doing well. And we’ve got articles linked to each of these recommendations for you.

                                We’ve also got something called Face Age. Face Age is an AI power tool where you can take a selfie and it will, based on a data set of more than 12 million people, be able to tell you how old your face looks biologically, your eye age, your skin health markers like wrinkling and pore size and so on. But most importantly, we then give you advice for how to improve all of these scores. It’s another metric that you can keep track of over the months or years ahead to see how that’s evolving with time. So, we’re trying to get as much out there for free for public consumption as possible.

Dr. Weitz:            That’s pretty cool content. Where is that available?

Chris:                   So, if you go to novoslabs.com/faceage, you’ll find that tool there.

Dr. Weitz:            Wow. Very cool.

Chris:                   It was just featured last week in Daily Mail, and we had more than a million people hit that in just a couple of days.

Dr. Weitz:            Really? Wow.

Chris:                   Yes.

Dr. Weitz:            Very cool. So, you guys developed the algorithm point?

Chris:                   We partnered with a team of researchers to develop the algorithm.

Dr. Weitz:            Wow. Very cool. All right, Chris, thank you very much and we’ll talk to you soon.

Chris:                   Thank you for having me, Ben.

 

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Dr. Weitz:            Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify, and give us a five-star ratings and review. That way, more people will discover the Rational Wellness Podcast.  And I wanted to let everybody know that I do have some openings for new patients, so I can see you for a functional medicine consultation for specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions, or for an executive health screen, and to help you promote longevity, and take a deeper dive into some of those factors that can lead to chronic diseases along the way. That usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing. And we’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective.  So, if you’re interested, please call my Santa Monica Weitz Sports Chiropractic and Nutrition office at 310-395-3111, and we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.

 

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Dr. Mark Pimentel discusses New Research Findings on SIBO and IBS at the Functional Medicine Discussion Group meeting on May 25, 2023 with moderator Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 

 

Podcast Highlights

4:24  Dr. Pimentel started a fellowship at Cedars in 1996 on motility and his colleagues questioned why he would want to get involved with treating IBS patients, who are psychologically altered?  Patients with IBS seemed like regular folks who were struggling and it is too easy to attribute medical conditions that are not well understood to psychological causes. He reflected on when heart disease was thought to be primarily due to stress and in the early 70s if you had a heart attack, you were told that you needed to quit your job.  But it turned out that what caused their heart attack was more due to the steakhouse with the cholesterol and the alcohol and the smoking and your genetics and all the other things we learned about cardiovascular disease.  One of his colleagues in 1996 told him that “IBS is a disease of hysterical women.”

5:41  Anti-diarrheals.  Even in the last three years, the AGA guidelines say that anti-diarrheals like Imodium should be first-line therapy for irritable bowel syndrome because they’re cheap.  This is not a good reason to recommend a medication, rather than trying to figure out the cause of IBS and then treating that.  This is because the research that Dr. Pimentel has conducted and published for the last 26 years that demonstrates that SIBO is the main cause of IBS has still not been fully accepted by the GI community. 

6:36  Food poisoning is the cause of about 60% of cases of IBS-D and there is now enough research data to prove this.  The bacteria that cause food poisoning, whether it be E. coli or Campylobacter or Shigella or Salmonella secrete an endotoxin–Cytolethal Distending Toxin (CDT) and specifically the B version of CTD–CDTB–that leads to SIBO/IBS.  The immune system reacts to the CDTB and those anti-CDTB antibodies end up cross reacting with a structural protein in the intestinal wall called Vinculin.  Thus the immune system is attacking the body, an auto-immune reaction.  This leads to damage of the nerves that control the intestinal cleansing waves, which leads to a buildup of the bacteria in the small intestine (SIBO).  These small intestinal cleansing waves are peristaltic waves that are occur when you haven’t eaten for more than 3 or 4 hours, which help to clear out excess bacteria.  These cleansing waves are caused by the deep muscular plexus-interstitial cells of Cajal.  Dr. Pimentel has developed a second generation test that measures antibodies to CDTB and to vinculin via blood testing that is extremely accurate, the IBS Smart test from Gemelli Biotech. 

25:37  Methane SIBO (IMO) does not appear to be caused by food poisoning.  By paralyzing the gut in the case of hydrogen and hydrogen sulfide SIBO, this can lead to diarrhea. In the case of methane, this causes the gut to hypercontract and this overcontraction of the gut muscles leads to constipation.

29:33  In a study published in 2020 Dr. Pimentel’s group showed that a lactulose breath test–not a glucose breath test–and using the 90 minute cutoff of more than 20 parts per million increase in hydrogen it correlated well with the bacteria in the gut seen in culture and the hydrogen-producing enzyme machinery in the small intestine was elevated.  This shows that the hydrogen is being produced in the small intestine and not in the colon. (Leite G, Morales W, Weitsman S, Celly S, Parodi G, Mathur R, Barlow GM, Sedighi R, Millan MJV, Rezaie A, Pimentel M. The duodenal microbiome is altered in small intestinal bacterial overgrowth. PLoS One. 2020 Jul 9;15(7):e0234906.)

30:33  For the first time in 26 years Dr. Pimentel and his group in a study presented at DDW this year have been able to validate a breath test by correlating it with culture done on MacConkey agar but not blood agar and the cutoff should be 10 to the 3 rather than 10 to the 5. And with a network analysis of the data you can see that the microbiome of the small intestine starts to get significantly disturbed by the time you get to an increase in the bacteria of 10 to the 3.  By the time you get to 10 to the 5, the diversity of the bacteria in the small intestine changes drastically with decreased diversity and mostly proteobacter.  With methanogens we know that Methanobrevibacter smithii is the bad actor and with hydrogen sulfide one of the bad actors is Fusobacterium varium, which is very aggressive and is seen in stool as well as in the small bowel.  The cutoff for hydrogen sulfide was originally five and then it became three and now two will be the new cutoff for a positive finding on the Lactulose 3 gas breath test.

36:11  Breath testing validation.  Dr. Pimentel’s group finally published a study that validates breath testing  and in fact a system of breath testing by comparing it to a microbiome analysis. (Villanueva-Millan MJ, Leite G, Wang J, et al. Methanogens and Hydrogen Sulfide Producing Bacteria Guide Distinct Gut Microbe Profiles and Irritable Bowel Syndrome Subtypes. Am J Gastroenterol. 2022 Dec 1;117(12):2055-2066.)  We also see that the patients with methane, the IBS-C patients, tend to have very low hydrogen levels because the methanogens consume hydrogen as fuel.

                                        

                       

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Dr. Mark Pimentel is a Gastroenterologist who is head of the Pimentel Laboratory and Executive Director of the Medically Associated Science and Technology (MAST) program at Cedars-Sinai, which is focused on the development of drugs, diagnostic tests, and devices related to condition of the microbiome, with a focus on IBS. Dr. Pimentel has published over 150 scientific papers and he has written two books, A New IBS Solution, and he cowrote The Microbiome Connection: Your Guide to IBS, SIBO, and Low-Fermentation Eating with Dr. Ali Rezaie.  Dr. Pimentel speaks around the world at conferences, esp. about SIBO and IBS. Here is a list of some of Dr. Pimentel’s key publications: https://www.cedars-sinai.edu/Research/Research-Labs/Pimentel-Lab/Publications.aspx

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

 

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Podcast Transcript

Dr. Weitz:                            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting-edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me and let’s jump into the podcast.

                                                I want to thank our sponsor for this evening which is Integrative Therapeutics. And I believe that Steve Snyder is on the line to tell us about a few Integrative Therapeutics products. Steve?

Steve Snyder:                    Actually, since we’re kind of already ready to go, we have a great new curcumin product that’s going like crazy. I’ll just put it in the chat and also an update to the Elemental Diet. I’ll put that in the chat, too. And if you have more questions, you can just catch me after.

Dr. Weitz:                            Maybe just tell us one thing really quick about the Elemental Diets because that’s a very important treatment option for patients with SIBO and IBS.

Steve Snyder:                      So, the big news on the Elemental Diet is that we’ve reformulated it which the big part of it is that there’s a much lower carb content to it. So, we used to be 22 grams of carbs per scoop. It’s now down to 15 grams. And we’ve raised the fat and the amino acid content so it’s still 150 calories per scoop. So, it’s much better tolerated. It’s not nearly as sweet. And we have basically already sold through all the old stuff. So if you’re getting it, you’re getting the new formula and it’s much better. So, there you go.

Dr. Weitz:                            Excellent. Thank you, Steve.

Steve Snyder:                      Yup.

Dr. Weitz:                            Let me introduce our guest. Dr. Mark Pimentel is the head of the Pimentel Lab and executive director of the Medically Associated Science and Technology Program at Cedars-Sinai and a very prolific researcher having published over 200 scientific papers. The Pimentel Lab researches the microbiome and irritable bowel syndrome, one of the most prevalent gastrointestinal conditions.  Thanks to Dr. Pimentel’s research, we now know that most cases of IBS are caused by small intestinal bacterial overgrowth, which now has three categories; hydrogen-dominant, hydrogen sulfide-dominant and intestinal methanogen overgrowth. Each of these subtypes can be diagnosed with the latest SIBO breath testing and this can help guide specific treatments for each subtype.

                                            I just read that ChatGPT, the artificial intelligence bot that passed the exam to become an MD and also to become a lawyer, but it failed the exam to become a gastroenterologist. So now, we know that gastroenterology is the most difficult medical field. Dr. Pimentel, very warm thanks for joining us again tonight.

Dr. Pimentel:                      Thank you so much, Ben. Yes, ChatGPT cannot become a gastroenterologist which is good for us. I’m not certain I’d want a colonoscopy from ChatGPT either. I’m sure they’ll figure that out one day.

                                           So, I’m going to talk a little bit about irritable bowel syndrome and the microbiome and SIBO. And just to introduce you a little bit, the MAST program is … I’m in my office which looks like a rubber room but it’s not. There’s a really nice lobby out there and a beautiful lab in the back. But this is what we do. Our job is to try and figure out the microbiome, unlock the secrets of the microbiome and see if we can help some people with what we do here. And so, super excited to have the facility we’re in now.  But I’ve actually redone some of these slides in a way this past month after DDW sort of reflecting on maybe my age or what, maybe I’m having a late life crisis or a midlife crisis, whatever you want to call it.

                                           But 1996 is when I started fellowship at Cedars and I reflect on what … People said, “Are you going into motility? Are you kidding? You’re going to treat all these IBS patients who are all psychologically altered?”   And it turns out that I understood it very differently when I started to see these patients and I didn’t think of them that way. In fact, they seemed like just regular folk, but they were struggling and suffering. But it was all because when in medicine we don’t know what’s going on, we often attribute it to stress, anxiety, depression and other things. And I also reflect back to the early ’70s where if you had a heart attack, you got to quit your job. You got to quit your CEO. You got to lie on a hammock on a beach and relax or you’re going to have another heart attack because your job is killing you.  But what it turned out to be was the steakhouse with the cholesterol and the meat that was killing you and all the alcohol you were drinking and smoking and your genetics and all the other things we learned about cardiovascular disease and we’re all under stress. So, I don’t know. Yeah. So this was sort of the thinking of the time.

                                                This is a true quote from one of my senior colleagues who said, “IBS is a disease of hysterical women,” which in the context of 2023 seems ridiculous. The final thing I’ll point out in this slide is anti-diarrheals. So, Imodium, okay, Imodium works for diarrhea. But even in the last three years, the AGA guideline on IBS says anti-diarrheals should be first-line therapy for irritable bowel syndrome because they’re cheap.  And my hair curls, it’s already kind of curling, but my hair curls because would you ever imagine that an anti-diarrheal would be first line for Crohn’s or ulcerative colitis? It would make the diarrhea better, but there’s no way they would put that in the guideline. Sure, it’s anti-diarrheal, it stops or reduces diarrhea but it’s not treating the disease. We’re still stuck. I mean, if the fact that the AGA still says this is first line is a little bit silly at this point. But anyways, we are where we are and it is what it is.

                                                I’m here to talk to you about this which is sort of the IBS pathophysiological sequence as we’ve studied it for 26 years, which I’ll try to argue explains about 60% of IBS-D. And the methane explains about the same amount of IBS-C or the constipation side of things. So, yeah, we’re not explaining all of IBS but if we get 60% of it figured out, the other 40% will need more time and more effort. But I think that’s a good start.

                                                So, all of these organisms, food poisoning organisms have a single toxin in common which I’ll discuss leading to autoimmunity, some nerve damage and bacterial overgrowth. And there’s a whole lot of stuff that came out at DDW here, the DDW is the Digestive Disease Week, that really is a capstone to the 26 years in a sense and I’ll explain it as I get there.  Well, what I like to do is I like to start with the bookends and say, “Well, does food poisoning cause IBS?” And the answer is yes. This is a review of 45 studies by the Mayo Clinic 2017. So this is a little dated in the sense that it’s five, six-year-old study. But the same thing is true today. If you add more studies to it, you just get greater power.

                                                If you have a hundred people who go to a wedding and the food is tainted with E. coli or Campylobacter, 11% of those people, if a hundred people get sick, 11% will end up with the irritable bowel syndrome as a result of that. So, IBS is caused by food poisoning. The question is what percentage? And what we believe based on mathematical modeling is that it’s about 60% of all of IBS could start from food poisoning.

                                                The second question is, okay, we’ve been sort of saying, and I’m going to get to SIBO later, but we’re sort of saying that bacterial overgrowth and SIBO are interrelated. Well, but can food poisoning lead to bacterial overgrowth? So, this required animal models. And in early as 2008, we actually did this study. We developed the first animal model, not the first animal model of post-infectious IBS, but the first animal model of post-infectious IBS using a bug that actually causes IBS in humans commonly and is the most common cause of gastroenteritis in the United States. And that’s Campylobacter jejuni.  And so, 33 rats on this side, 33 on that side. Three months later after the infection is cleared, so really a total of four months, we then were able to quantitate the bacteria and look at their stool for consistency just before euthanasia. And you can see 27% of the rats who got Campylobacter now have SIBO. So, food poisoning can cause SIBO. Humans, food poisoning can cause IBS. We know IBS and SIBO are related.  And so, this is the first animal model that shows that when you get Campylobacter and you develop SIBO, the rats have altered stool consistency. So they’re getting an IBS phenotype. But it’s more deep than this and I’m going to show you some stuff at DDW that will really, I hope, impress you.

                                                But if you fast forward to 2022, I’m skipping a lot of studies because we only have a certain amount of time tonight. It would take me three hours to go through all the research to get to this particular summary. The Bradford Hill Criteria is sort of like the gold standard for, “Okay, does a bug cause a disease? What is the evidence?” And you have to meet all these criteria to be the strongest evidence. And this notion that Campylobacter causes IBS meets all the criteria.   So, this is pretty impressive. We finally have a cause for IBS and it’s food poisoning and it’s Campylobacter, but we just now need to iron out or understand the nuts and bolts in between, which is what I’ll take you through or part of that journey. So, here’s what that is about, the nuts and bolts in between. You’ve got the CdtB toxin and maybe some autoimmunity that develops that causes nerve damage. So, let’s work through that.

                                                Well, all four of these organisms, Shigella, Salmonella, Campylobacter, E. coli, look, they all look different. But they only share one specific toxin in common and that’s the CdtB toxin. And this is the active part of that toxin. It’s an A, B and a C and the B is the active agent. So, we had done some studies where we deleted the toxin from Campylobacter and administered that Campylobacter to animals and they did better. They didn’t get as much IBS.

                                                And then, if you look at what the animals were reacting to, so in other words, you get food poisoning, you get exposed to the CdtB toxin and you end up forming antibodies to this, vinculin. And vinculin is right at the end of these actin filaments, the green filaments in the cell which are the skeleton of the cell to keep its shape. And you can see it’s like the vinculin is stretching the cell out to reach out to its partner.

                                                And I don’t have time to go into detail of the different kinds of vinculin other than the body, but there’s really only one type where you get this autoimmunity and it’s the 117 kilodalton vinculin. But that 117 kilodalton vinculin happens to be important for the cells that make the cleaning wave of the gut called the deep muscular plexus-interstitial cells of Cajal.

                                                If you look at the top panel, that’s the healthy animals. A lot of these cells, a lot of these cells. If you go to the middle panel, that’s the Campylobacter-treated animals but do not have SIBO. So they still have the cells but they’re a little vague. But if you got SIBO and you had Campylobacter, the number is diminished. And not only is it diminished, you can see that when you count them, and this was a pathologist counting it blindly, you can see there’s a reduction in ICCs. And these are the cells that drive the cleaning wave.

                                                So, is the cleaning wave damaged in irritable bowel syndrome with SIBO? We actually showed that even before that other study that in 2002, we showed that if you take IBS patients with SIBO and compare them to healthy controls and you put a tube through their nose into the small bowel and measure cleaning waves, the IBS with SIBO patients have weigh less. Not only weigh less, 50% of the IBS patients, none, no cleaning waves in four hours of fasting. So, it is quite damaged in the case of the SIBO patients.   Well, we know from as early as 1977 that if you don’t have cleaning waves, you get overgrowth. This is Vantrappen who’s one of the great physiologists of the last generation and he discovered this. OK. So, now that we have an understanding that maybe CdtB is related to SIBO in some way, let’s really sink our teeth into this.

                                                And what I mean by that is maybe you don’t even need Campylobacter. Maybe all you do need to do is CdtB toxin. And that’s what we did here. We purified the CdtB toxin and we administered it to rats like a vaccine. So they get a shot under the skin in the back. They don’t get it in the gut. They don’t get it through the mouth. They get it in the skin. And then three weeks later, they get a booster.

                                                And of course, they didn’t have antibodies to CdtB before but they sure do after the vaccination. And so, the CdtB antibodies go way up. But look what other antibody goes up after, vinculin antibodies. So the rats exposed to CdtB developed autoimmunity to vinculin which is basically molecular mimicry, which I’ll show you in a second.

                                                But they also got SIBO. So, remember, we injected the CdtB under the skin, they formed these antibodies. And now in their gut, they have more bacteria in the duodenum and more in the ileum. And the vinculin expression, meaning the amount of vinculin in the gut tissue is reduced. So, this antibody is going after vinculin in the gut. And by doing so, we believe it’s causing this overgrowth of bacteria.

                                                So, we think it kind of works like this. You get CdtB exposed. You don’t like CdtB, you don’t like any of it, so you’re forming antibody here and antibody here and one here. But CdtB kind of looks a little like vinculin in that one area and therefore you get this autoimmunity. And that term is molecular mimicry. CdtB is mimicking vinculin in order for you to do something to yourself and create autoimmunity.   So, this is from last year’s DDW but this paper is literally on the verge of publication. We have a major revision at a journal and we’re just fixing that up and we hope to get that back and get that published sometime in the next month or so. So, we’re very close for this to be officially published. But it was presented. So it was presented at DDW last year so it’s open to the public so I can talk about it.

                                                But this is the same experiment again, but a deeper, deeper understanding. So, let me show you. And I’m talking about microbiome now. So, we did it again. We gave CdtB this group, nothing to this group. You see they don’t get antibodies to CdtB. They sure do get antibodies. Because they got the antibodies, their wet weight of the stool went up. And the higher the antibodies were, the wetter the stool was. So, this is pretty good evidence.  Second thing is nothing happened to the colon bacteria. Control, CdtB, control, CdtB. All the big changes were in the small intestine which was very interesting. Again remember, the CdtB is injected under the skin of the rat. It’s not injected in the gut.

                                                But what really was interesting was, so the control group, this is where the microbiome sits as a whole. So, the orange balls are the control animals. Three months later, the green balls are the CdtB-treated animals, three months later. And they didn’t change. Because the animals, like the people at the wedding I talked about at the beginning of my presentation, not everybody gets IBS.

                                                And so, what happens is a group stays like controls. A second group gets increased bacteria but of the E. coli type here which is a hydrogen producer. And a third group goes in the Desulfovibrio direction and they’re the hydrogen sulfide group. So the rats in the development of diarrhea IBS in this model develop two micro types, hydrogen-producing E. coli or hydrogen sulfide-producing Desulfovibrio. And you will see that when we get to the micro types that we just published in humans, it’s the same. So, hang on to that thought of the two micro types in D.

                                                I show this slide, it’s a bit complicated. We took these animals. We took their small bowel. And we looked at what was changing in the small bowel as a result of this CdtB. So, the CdtB, again under the skin. And then the proteins and things that are produced by the small bowel, what’s going on there at that level to create the problems that we know are quote IBS? And that’s this. But I’m going to show it in another slide to summarize it so you understand what’s actually happening.

                                                So, I think I got that down here. I don’t want to miss it. But if I don’t, I’ll come back to it. But basically, there are three things that happen. You get impaired barrier function as a result. You get a change in motility, meaning the proteins that control barrier function are negatively impacted by the CdtB. The proteins that control the signaling for motility are changed in a bad way. And then, you get enhanced visceral sensitivity which is what we know as pain in IBS and visceral hypersensitivity in IBS. So the animal model can explain the entire spectrum of what is irritable bowel syndrome.

                                                Okay. So now, we have these two antibodies and the question is, “Can we diagnose IBS using these antibodies?” Well, we did a first-generation antibody test. And the first-generation antibody test was okay. But then we realized that these proteins are really wonky. That’s not a medical term. But they’re wonky, they’re a little unusual. And you need to treat the proteins in a special way to allow the areas where the antibodies bind to be more accessible. And that’s called epitope optimization.  And so, we performed epitope optimization and we developed a second-generation test. And you can see that if you have anti-CdtB elevated, it’s way higher than IBD. Vinculin, even more impressively differentiating IBS-D from other causes of diarrhea like Crohn’s, ulcerative colitis and so forth.

                                                But this is the most important slide. Look at if you’re positive for both markers, even if you’re positive for one or the other, you’re over 80% post-test probability. And that’s medical certainty. Anything over 80% post-test probability is considered medical certainty. People say, “Well, look, the sensitivity is low.” If you do an either/or, this number will be 56. In the normal testing world, 56% sensitivity, yeah, maybe that’s not so great.

                                                But remember that out of a hundred IBS-D patients, we believe only 60 came from food poisoning. And this is a marker for food poisoning as a cause of IBS, not IBS total. So, if we’re at 56% and 60 is the number we want to get to, then we’re darn close to perfect here. The specificity is over 90%. But look at the likelihood ratio. And this is what determines your post-test probability.

                                                Look at the first-generation test. It’s a 2 and a 5.2. It’s now a 5.3 and a 6.3. Let me show you what that means. So, I’m going to show you every test that’s ever been developed for irritable bowel syndrome. So, pain perception does nothing. So by the way, the pre-test probability of IBS if you see a doctor is about 55%. So, you want to get above 55 with your nomogram using the likelihood ratio.    There was a 34 biomarker panel, got you to 74. That’s not on the market anymore. Bile acids in stool doesn’t get you to 80. The 10 biomarker panel from another company, not on the market anymore, doesn’t get you to 80. Visceral hyperalgesia, if you blow a balloon in the rectum and they get pain at an earlier time. Nobody does this, very complicated. Actually a little bit morbid for the patient. But it’s not bad, it’s over 80.

                                                Volatiles in the stool, not available, but people are studying this and they’re getting some decent results. Look at the first-generation blood test for IBS that we developed. It only gets you to 60 if it’s just vinculin. And it gets you to 80 if you’re a CdtB. Look at what we did to optimize it in the second-generation. Vinculin, CdtB. And if both are positive, the post-test probability is 98%.

                                                So this second-generation test, so there’s only one company with the second-generation test, all the other CdtB and vinculin are using first-generation technology and they just don’t cut it. I mean, they don’t get any … Well, they’re certainly not 80% or 80 with vinculin. And CdtB just barely scratches the surface. So, you have to get the second generation if you want the most accurate test.

                                                And so, it kind of works like this. You’ve got all this beautiful bacteria, all sorts of different shapes and sizes and colors. And then, you get Campylobacter which are the green organisms with the flagella here. They give you the CdtB. You form antibodies to CdtB. And then, you later form antibodies to vinculin. And that takes about two to three months after the food poisoning. Some people never form the autoantibodies. And as these go down, their IBS goes away.  But if you form these anti-vinculin, you’re stuck. You get this change in the nerves. And then you get a buildup of these blue characters which are the bacterial overgrowth. And that leads me to bacterial overgrowth.

                                                So, I’m going to show you some new data, really hot off the press data. So, what we know is that breath testing is abnormal. This is a 2020 meta-analysis. Breath testing is abnormal in IBS, full stop. So, there was a lot of criticism of breath testing because it’s an indirect technique.  So, what does breath testing mean? Is it transit? Is it colon bacteria? Is it small bowel bacteria? And to be honest, if you go back to the 1980s and ’90s, we only had hydrogen back then. And that really looking back was absurd because hydrogen is a fuel for hydrogen sulfide and methane. So if you don’t know methane and you don’t know hydrogen sulfide, you can’t know what the hydrogen level is because the hydrogen’s being used up.  So, if you have … I’ll show you a study that was just published from us. When methane’s there, hydrogen’s down because it’s not that it’s down, it’s being produced a lot, but the methanogens are eating it up. Four hydrogens to make one methane. Five hydrogens to make one H2S.  So, that’s part of the problem with trying to determine if the hydrogen level is high or low. You don’t know because you’ve got these consumers over here on the right. And it turns out methane is what’s causing constipation. And it turns out hydrogen sulfide is what’s leading to or at least associated with diarrhea. So you really got to measure all three gases or you’re kind of in the dark as to what’s going on.

Dr. Weitz:                          And Dr. Pimentel, we don’t think that methane is related to food poisoning?

Dr. Pimentel:                     Yeah. So, the antibodies that I was talking about earlier, they’re only present in about 20% of people with IBS-C. So, whereas 56% of patients with IBS-D have one or either antibody. So, yeah, food poisoning is more the D side.

Dr. Weitz:                          And it’s kind of ironic because by damaging vinculin, you’re damaging motility. And we normally think of constipation as being related to motility problems.

Dr. Pimentel:                     I’m not going to cover that today, but that leads to one other thing about methane. I’ll talk about methane in a minute, but I’m not getting into the details that I think you want to hear. Methane doesn’t paralyze the gut to cause constipation. It causes the gut to hypercontract.  And remember, if your gut is paralyzed, it becomes like a funnel and just drains things through. So the way you cause constipation is you cause the gut to stop moving and hold things. And so, what we see with methane patients is you get these contractions, not like this nice-flowing contractions. It’s like we’re going to hold everything here contractions. We call that segmental contractions versus peristaltic contractions. So methane switches your gears to hold everything as opposed to move everything along.  But in the case of vinculin, vinculin is doing damage to just the cells that cause the cleaning waves. So, you’re just affecting the small bowel microbiome and methanogens are both small and large bowel. And I’ll show you the new data on that which is really interesting.

                                                So even though there were criticisms about breath testing, all this time, people were starting to do culture as quote the gold standard. And I’ll talk a little bit about that later with some new data. But here’s the first culture study 2007 in Sweden. Clearly, IBS has more bacteria in the small bowel.

                                                This is I would argue the most important study because it determines the benchmark number. Again, 60%, similar to the food poisoning thing. This is D, again diarrhea aside. 60% of IBS-D patients in this trial had the cutoff of greater than 10 to the 3 or greater than a thousand bacteria per ML in the small bowel. So, they had overgrowth.

                                                And that leads me to the REIMAGINE study which is what we’re doing at Cedars here for the last few years. And this is a very difficult undertaking because nobody has ever looked at the small bowel microbiome until we started to look at it systematically in the way we have. So, we’re basically taking people who come in for upper endoscopy and no colonoscopy and getting their juice and measuring the bugs in their juice.

                                                And so by doing this, we looked at SIBO. And this is a paper we published now two or three years ago. And you can see that every ring represents a different level of life. So, the kingdom is bacteria, the phylum is here. And you can see right at the phylum level already in SIBO, Proteobacteria is taking up a huge chunk versus non-SIBO.

                                                Okay. And then when you get to, now we’re doing 16s sequencing here. You’re probably familiar with that term 16s sequencing. You’re sequencing the ribosomal RNA of the bacteria. Now, you can get pretty good at identifying bacteria by sequencing ribosomal RNA, but you can’t get past the genus level. So we’ve got Klebsiella and Escherichia, which are taking up the bulk of SIBO. But you’ll see in a minute, we did now in DDW.

                                                But in this study, what we showed is that when you do a lactulose breath test, not glucose, lactulose breath test, and using the cutoff that the experts have all agreed in, 90 minutes, more than 20 parts per million rise in hydrogen. It correlated very nicely with culture. It correlated very nicely with the bacteria of the gut.

                                                And when that was present, when you had SIBO defined by breath test, your hydrogen-producing enzyme machinery in the small intestine was elevated. So, for those who say, “Oh, the hydrogen’s coming from the colon, the lactulose is getting to the colon,” that doesn’t jive with this data. The hydrogen-producing machinery is up in the small bowel. We’re not taking juice from the colon, we’re taking it from the small bowel. It’s up when you have this positive breath test.

                                                But now, let’s go to DDW. Now, we’re really, for the first time, I know this sounds just bizarre. I’ve been talking about SIBO and breath testing for 26 years. But honestly, this DDW, we finally validated a breath test. And let me show you what I mean by that.

                                                So, if you look at culturing the bowel, some groups just culture MacConkey agar, blood agar, anaerobic, aerobic, add up all the colonies on the plates and say, “Okay, is it over 10 to the 5 or not?” Well, 10 to the 5 is not the cutoff, it’s 10 to the 3.

                                                And you can see this is the diversity chart so diversity on the y-axis. And you can see that SIBO has a lower diversity based on culture. But blood agar doesn’t distinguish SIBO at all. The diversity is no different whether it’s 10 to the 5, 10 to the 3 or lower than 10 to the 3. On MacConkey agar is where you see the microbiome deteriorating.

                                                So, let’s take that one step further. This is a network analysis. So a network analysis is like, okay, you got a city and every one of these little round circles is a occupation. In here, it’s a microbiome, it’s a microbe. But let’s call it an occupation. So you’ve got doctors. You’ve got lawyers. You’ve got bakers. You’ve got plumbers. You’ve got gas station workers. You’ve got sanitation workers. You need everybody in harmony in the right proportion interconnected so the city is healthy. So the more interconnected this looks, the better the city, the better the function. And so, this is a healthy human non-SIBO.  And the tipping point for the microbiome to go awry is 10 to the 3. It’s falling apart already. And this is on MacConkey agar. And then when it goes to greater than 10 to the 5, look at this, there’s nothing left. Everything is just destroyed. So, it’s as if you’ve put too many of one character in the city and everybody’s leaving the city, we’re done. Or it’s like the city’s full of criminals and now everybody’s leaving the city because it’s dangerous. And that’s sort of what happens in SIBO.  But I’m going to give you even more details, which is even more exciting in a minute.

                                               Quickly on methanogens, we know the methanogen now. We’ve been working on this for years. M. smithii is the bad actor. It produces high methane and that causes the constipation and the bloating.  This DDW, for the first time, we’re able to see exactly where the methanogens live in humans using sequencing. And it’s in the duodenum and it’s in stool. And it’s usually that Methanobrevibacter smithii that’s causing the trouble. And so, that’s why we changed … We believed that to be true and that’s why we changed the name to intestinal methanogen overgrowth and not SIBO methane. It’s intestinal methanogen overgrowth because it’s not just small bowel, it’s everywhere. And when it goes up, it goes up everywhere.

                                                And then finally, the hydrogen sulfide-producers, we have a lot of data on this character which is Fusobacterium varium, a very aggressive-

Dr. Weitz:                          Dr. Pimentel, let me just ask a quick question. So, the fact that methane is IMO, does that mean ideally, to see significant improvement in symptoms, we need to treat the colon as well as the small bowel?

Dr. Pimentel:                     You need to get the methane down. And if the methane’s coming from the colon and the small bowel which I believe that’s true in the case of methanogens, you have to get the methane down by reducing those organisms in both locations. That is correct.

Dr. Weitz:                          And that could be one reason why rifaximin may not be as effective for methane.

Dr. Pimentel:                     By itself, correct.

Dr. Weitz:                          Right.

Dr. Pimentel:                     Yeah. And we combine it. Yeah, you’re right. And then I’m going to show at least that one study a little bit later. Now, hydrogen sulfide, as I said here, hydrogen sulfide is associated with diarrhea. It’s a different animal because hydrogen sulfide is very reactive. So, the transport of hydrogen sulfide in breath in a bag or in a tube, it’s not stable. So you have to get a very special material to construct the bag.  You have to be able to prove that that transports and that it measures things correctly. You’ve got to develop an instrument that measures all three gases without cross-reacting with each other with the sensors and the orientation of those sensors in the instrument.  And then, you got to do a study to create a cutoff. So, the original cutoff was five and I’ll show you that. And then it became three. And now it’s moving to two and I’ll show you why. It’s always better when you start a new technology that you don’t say, “Oh, anything over one is positive,” because then everybody’s positive. And then, people are disappointed when the science says, “No, no, no, no, it’s two.”   We don’t want to overtreat our patients until we know the science. The first science said if you take a diarrhea patient, this is not D IBS, this was functional diarrhea. They were over five. So, diarrhea patients are over five, generally speaking. And the more severe the diarrhea, the higher hydrogen sulfide. But we learned a lot about hydrogen sulfide in this study. And I’m going to show you another study later that says two is a better cutoff.  But let me just set this study up because this is the first and this is published now as of December 2022.

                                              This is the first study in all the years of breath testing that compares a system of breath testing. And what I mean by that is the bags, the patient, the mailing to the company, the instrument, the result and the patient having either constipation or diarrhea, and that the gases on this whole system correlates with the microbiome. Never been done with a breath test in this way.  And you’ll see the results and you’ll see for yourself that for the first time, there’s a breath test that actually does correlate with the components or micro types of the microbiome. So, it’s a double-blind study for IBS-D, not of SIBO study. It’s a double-blind study for IBS-C. So D is here, C is these two. And they all had breath tests and they all provided samples so we could do the microbiome.  You can see that … Let’s look at D which is blue and look at their breath test just focusing on methane on the breath test. D patients, nada. We didn’t hand-select these for SIBO or non-SIBO, these were just D patients. In the C group, not all of the C had methane. You can see some of the Cs are this orange line down here, but the ones who did have methane, they’re up here. They have a lot of methane and they start with methane. They don’t go up with the sugar, with the lactulose.

                                                Now, I want to focus on hydrogen only. So you’ve got the same three groups. Look at hydrogen. By 90 minutes, in just unselected D patients, you’re already over 20 on average. Yes, there are some who are negative. Yes, there are some who are even higher. But on average, they have SIBO.  Look at the C patients with methane. They have the lowest hydrogen. But I already told you the secret answer to that. Methane patients eat hydrogen. So, they have to have hydrogen. You can’t make methane without hydrogen. So, they’re eating the hydrogen.  So, if you only measured hydrogen on your breath test, that patient would have been a low hydrogen. You wouldn’t know. You have to measure methane. The same thing is happening for hydrogen sulfide. Look at hydrogen sulfide on this test. It’s higher in D and not in C. So, you’ve got to measure all three gases.

                                                But this is the part I was trying to get to and this exciting part that if you have methane on your breath test, M. smithii is elevated. Not just that, it correlates. So the higher the methane levels, the higher the M. smithii was in stool. And the higher the methane levels were and the M. smithii was in stool, the lower your hydrogen got at the end of the breath test with lactulose because all the hydrogen’s being shunted to methane. It’s a negative correlation.

                                                So then, everything’s fitting for the first time looking at breath test, really complicated diagram. Everything with stars in it is statistically significant but let me focus on a couple of things. When the methane, when it’s blue, it’s a positive correlation. When it’s orange or red, it’s a negative correlation. You could tell by the graph here. So hydrogen is down if the methanogen is up. Methane is up if the methanogen is up. And so, that’s how it goes.

                                                But let’s move through. The hydrogen producers that are producing the hydrogen for methane are not E. coli and Klebsiella. They are Christensenella and Ruminococcaceae. And if you want ask more questions about that, we can do that at the end. But we now know sort of the micro type of methanogenesis and it’s not what we used to think.

                                                Okay. So let’s go now to hydrogen. And breath hydrogen is negatively correlated with methane. I’ve already said that. Fusobacterium, positively correlated with hydrogen sulfides. So this is your hydrogen sulfide-producer. And I’m going to go to this. This is basically the same as this just in a more easy to read format.

                                                So, if you’re methane and you’re constipated, these are the enzymes that are upregulated in your gut. Methane production, this is objective measurement. I’m not making this up. This was actually the output from the science. And F420 which is the methanogenesis enzyme. If you’re IBS-D, it’s hydrogen sulfide pathways that are elevated.

                                                So in this study, we defined finally the two micro types for D which are hydrogen E. coli micro type and Desulfovibrio and Fusobacterium hydrogen sulfide micro type, the same as the rats. The rats didn’t get C but this is the C micro type which is Methanobrevibacter. And then these two characters which are the synthroph. Synthroph means your buddy who’s giving you hydrogen or the partner that allows this organism to flourish. So, these three guys go together and these characters go together and break down into two micro types, three total if you look at the whole IBS group.

                                                So now, we started in 2018. We did a consensus on breath testing. Well, the Europeans came along and they said, “We were doing our own consensus.” The Asia-Pacific Australian Group got together and they’re saying, “Now, we’re doing our consensus.” But the bottom line is they’re all about the same. They agree on the criteria of SIBO. They agree on the dosing of the substrates. And they mostly agree that SIBO and IBS are interrelated.

                                                Okay. And now, we have an app that we use. Patients take the app and they take a picture of their stool. The problem with research in IBS is that the patient at the end of the day if they’ve had six stools, which one are they reporting in terms of diarrhea or constipation? Is it the last one they had? Is it the first one they had? Is it because they had six today that they decide what they’re going to put? None of that matters. They take pictures of every stool. We get all of it.

                                                So, we’re able to see exactly what the stool looks like. And basically if you’re methane positive, you’re more constipated. If your hydrogen sulfide positive, you are more diarrhea, more stool volume. But look at when it starts to go up, two. That’s when it’s already statistically elevating. And so, we think two is the proper cutoff because that’s when the diarrhea and the volume of stool is increasing.

                                                Okay. And then I promise one final sort of bit of stuff here. At DDW for the first time again, the small bowel has been sequenced using shotgun sequencing. Different shotgun, it is not 16s, it’s sequencing all the genes, all the DNA of the bacteria. And so, it’s whole genome sequencing. And you’re able to get to the actual species and even strain.

                                                So, let’s look at SIBO versus non-SIBO. Non-SIBO on the left, SIBO on the right. Still, Proteobacteria but look at what’s going on here. This is non-SIBO. More than 50% of everything in the small bowel of a SIBO patient is Proteobacteria. But look at who’s there. One species of Kleb and one species of Escherichia, I’m going to tell you the names of in a second, are taking up nearly half the microbiome. So, it’s literally like an infection.

                                                So, let’s break it down because it’s two species when we get to this low. It’s Kleb. pneumoniae which is taking up 18% of everything, a little bit of aerogenous and then E. coli. E. coli is taking up the other 20%. Now, you see a bunch of E. colis here. These are the strains that are part of it.

                                                But 28% plus 18%, we’re talking about almost … It’s 46% if you add those two together, 46% of the micro biomark, two species. We thought SIBO is just colon back in the beginning like 26 years ago, “Oh, the colon bacteria are blooming in the small bowel.” That’s not it. We thought, “Okay, coliforms are blooming in the small bowel.” That’s not it. It’s two species only, E. coli and Klebsiella, that’s it, Klebsiella pneumoniae specifically.

                                                And when you look at the strains, it even gets even narrower. These two strains, especially K12, correlates with bloating, correlates with gas, correlates with abdominal pain, correlates with diarrhea and correlates with urgency. So, one strain is actually causing a lot of the symptoms. And in the case of Klebsiella aerogenes is worse than the pneumoniae.  So, then when we looked at the metabolic function of these bacteria based on their genome, so this is true metabolic capacity now. We’re not doing 16s. This is deep sequencing. This is shotgun sequencing. Look at the ability to digest carbohydrates.

                                                Now, when I say glucose degradation, it really means all of these things are representing carbohydrate digestion potential. So, the gut of a patient with SIBO is 63 times more powerful at breaking down carbohydrates in a period of time, you could say it like that, than a normal person. So it’s no surprise that if you’re eating non-digestible products or non-digestible carbohydrates, you’re fired up. Your engines are on full alert to break down these sugars and hydrogen-producing pathways are all upregulated.

                                                This is why low FODMAP can work. This is why low fermentation can work because these pathways are so jacked up. Hydrogen sulfides jacked up. And then, some of these histamine pathways are jacked up which could be why people get food sensitivities. We need to do more work on this. It’s just the beginning of trying to understand what’s going on with this microbiome.  But then looking at this network, this city, this harmonious city on the left, that’s normal. As soon as E. coli goes up a little bit and then goes up more, everything breaks apart. So now, we’re not talking about just culture, we’re talking about just one organism going up. And Klebsiella, it’s a disaster. So as soon as Klebsiella starts to go up, the whole network starts to fall apart. The city falls apart.

                                                So, you got to measure all three gases. For the first time in history, these three gases using this test, you’re able to know what the microbiome is doing because these gases correlate with the exact microbiome we see on sequencing and the symptoms. So, for the first time, we’ve really validated breath test. If you use this system, this system is proven.   So, this is what I tried to show you today in a brief presentation because I could spend hours going through all the data for all the different points because there’s so much to talk about now. But food poisoning starts to process. And then this toxin we believe is causing autoimmunity, changing the gut nerves. And then that leads to stasis or reduction in migrating motor complexes, leads to overgrowth now proven by breath test, by culture, by PCR, by deep sequencing both 16s and now shotgun sequencing, which is why IBS is antibiotic responsive.

                                                Well, let’s talk a little bit about treatment because that’s really what it boils down to for people. Rifaximin was FDA approved on the basis that IBS was a microbiome in part condition. And I think we now know more about how rifaximin is working than even when it was approved based on what I just told you.  But we do know even from 2019 that if your breath test is positive, you’re much more likely to respond to rifaximin. And if you make that breath test negative, that’s the patient who responds best to rifaximin. So even then, the signal was there.

                                                When it comes to methane, this is the only double-blind study we had. Neomycin alone doesn’t do it. Neo plus rifaximin does it. And it makes the constipation better and the methane go down. Now, as Ben was saying, maybe rifaximin gets part of it down, neomycin gets the other part down or maybe they’re synergistic in some way. We don’t understand why the two of them are required.  Now, I’ll explain a little bit about neomycin and the problems with neomycin right now that have probably been resolved, but we’ll get to that in a minute. For hydrogen sulfide, the only thing we can lean on is this bismuth study from the 1990s. So, we actually use this with rifaximin as I’ll show you. That’s what I do in my practice, but not a lot of data using rifaximin and bismuth yet although we’re collecting patients.

                                                So, this is my way of doing things in my clinic. You can use the data as you wish and decide on your own how you want to do things. But if I have a patient with chronic diarrhea or mixed, I want to know if they have these antibodies because if they do, it changes how I have to treat the patient. It changes how I tell them to travel. Be more careful because this anti-vinculin antibody, in my experience, the higher it is, the harder the patient is to treat.

                                                I do the three gas breath test on everybody now because now, we’ve validated this three gas breath test against the microbiome and now it’s very clear. And so, if they’re hydrogen, I try to give them rifaximin alone. If they’re hydrogen sulfide in my practice, I use rifaximin with bismuth. I sometimes travel prophylax them if they’re vinculin antibody is really high.

                                                And I do follow these antibodies because if they only have CdtB, it will go down with time and then they might come off everything. I’ve got patients who are done. Their IBS disappeared as we watch the anti-CdtB disappear. And then I start to withdraw therapy.

                                                In the constipation side, I don’t know. I don’t really do the antibody test because it’s only about 20 to 25% that are positive. I’m not sure it’s as cost-effective as it is in the diarrhea side. I do the three gas breath test again for one other reason which I didn’t mention. We do see this quite often. If you have hydrogen sulfide and you have methane, let’s say you have both positive, methane wins. And what I mean by that is you’re constipated, methane overpowers the diarrhea effect of hydrogen sulfide.

                                                But if you treat the methane and the hydrogen sulfide is there, you could have diarrhea because the hydrogen sulfide will be unleashed, so to speak. So we do see these changes in dynamics in the three gases depending upon what we use to treat. But if it’s methane, I use rifaximin and neomycin because the double-blind study supports that.

                                                You could substitute neomycin for metronidazole. We do that in our practice. When patients are either allergic or other reasons like kidney function, we use metronidazole. But recently, neomycin was not available. So the generic company that makes neomycin had some trouble with supply chain and had to I guess shift gears to make other products in their product line. But now, neomycin is available again. So, I’m thankful for that because I thought they were getting rid of it all together.

                                                So, here we go. Circa 1996, I’m going back to the beginning of my presentation again. This is what we thought of IBS. This is how we treated IBS. This is how we treated the women with IBS by saying these sorts of things or feeling these sorts of things. And this is now what we know using the microbiome studies that we’ve done over the years. There’s stuff in here I hadn’t talked about because we just don’t have time, but lot is going on now.

                                                So in conclusion, IBS is commonly a small bowel microbiome disease. SIBO is an important contributor to this IBS. E. coli, Klebsiella, two species, who knew? I mean, that’s what’s causing SIBO and it’s accounting for the hydrogen. And if you get rid of hydrogen, as I showed you on that breath test study, the IBS gets better.

                                                This is the character. M. smithii for methane causing constipation. Get rid of that, get rid of the methane, the constipation gets better. Hydrogen sulfide, now we need to know this one to understand more completely the diarrhea. And we see in our practice, we need to do more studies. We have one randomized control trial which I can’t talk about that shows that hydrogen sulfide goes down, diarrhea gets better. But I can’t talk about the drug yet. We’re still working on it.

                                                This new three gas breath test is the first breath test ever validated against the human microbiome. So, the whole system works in that breath test and you can rely on it. Second-generation testing, it’s the only one that actually gets you above the threshold of 80, which means it’s medically accurate.

                                                And now that we all know all this stuff, new treatments are coming, we’re developing new treatments. Right now, we’re doing an experiment in the lab trying to block methane with some chemicals and drugs that we have. I was doing that earlier today with our lab people. So, lots going on. Very exciting time.

Dr. Weitz:                            Excellent, excellent. I’d like to ask a question that’s coming from Dr. Rahbar who I guess didn’t make it. But is it true … It’s a several part question and it relates to potential relationship between archaea and fungal overgrowth.

Dr. Pimentel:                     Yeah.

Dr. Weitz:                          So the first question is, is archaea generally need an anaerobic environment?

Dr. Pimentel:                     So, archaea are generally strict anaerobes so they generally need strict lack of oxygen. But remember, we say that and yet in the small bowel where we believe there’s more oxygen because it’s a more vascular area, they’re growing. And so, the problem is if you have a lot of bacteria in the small bowel eating up oxygen, then maybe it makes it relatively oxygen-deficient. And so, we don’t understand that dynamic completely, but certainly stool is more anaerobic and more likely.   But methanogens, we did our first SIFO, fungal overgrowth data at DDW also. And SIFO, anything over 10 to the 3, it correlates with symptoms. So, we’re starting to see SIFO less common but it’s there. And it doesn’t correlate with methanogens, but it does correlate with SIBO. So, what I mean is you can have SIBO and you will have no SIFO. But if you have SIFO, you often have SIBO at the same time. Does that make sense?

Dr. Weitz:                            Yes. Now, it is the case that there’s a number of doctors, especially in the functional medicine type space, who feel that treating fungal overgrowth helps patients with methane, SIBO. And so, the thought is that perhaps fungal overgrowth is making the small bowel more anaerobic. And apparently, there is some data that when you’re trying to grow methanogens in the lab, they add fungi to the dish to facilitate that.

Dr. Pimentel:                     Yeah. So, I don’t know that data. I’d love if somebody has it to send it to me because I’d love to read it. But I had have not seen that study. What we do see in the microbiome of the duodenum is that we don’t see methanogens go up when we see the fungal go up, but we do see SIBO go up. But it may be different in the colon. So, maybe exactly what you say on the colon. I don’t have an answer to that from our data yet, but we certainly have all the sequences so we can check that.

Dr. Weitz:                            Okay. Let’s see.

Dr. Pimentel:                     You want me to go through the questions or are you going to go ahead?

Dr. Weitz:                            Yeah. Carrie, you’re asking about relationship between probiotics. What is this over under-absorption of fat in the small intestine, Carrie?

Carrie:                                   I was up in the middle of the night.

Dr. Pimentel:                     Oh, lost.

Dr. Weitz:                            Yes. Are you there, Carrie?

Dr. Pimentel:                     You’re on mute, Carrie.

Carrie:                                   Sorry. Hi. So, I was up in the middle of the night reading about SIBO like nighttime read. And I was curious about the effect of fat absorption on SIBO because I see a lot of people with SIBO that don’t absorb fat well. And I came across a study that was finding a correlation between certain probiotics that could improve the fat absorption and also hinder the fat absorption in people that were hyper-absorbing.   And they didn’t mention what they were. And I was curious if you have read anything about that, heard anything about that, could talk to that at all?

Dr. Pimentel:                     Not in those specific terms but what we do know is that when SIBO is present, there is a change in bile acid degradation. And you can often get bile acid being converted prematurely like in the small bowel instead of the colon into these more toxic bile acids. But also inhibiting because you’ve degenerated the bile acids, maybe it will inhibit the absorption of fat because bile acids are critical for fat absorption. So, it’s possible to get fat malabsorption with SIBO. And that’s been seen in the past.

                                                In terms of probiotics, what’s interesting and I’m not going to dive too deep into probiotics unless you want me to. But one of the things we see over and over and this is going to maybe surprise to maybe some of you or maybe you already know this, lactobacillus does no good for this small bowel. It’s a disruptor like E. coli and Klebsiella. So, it’s like the gang moved into town and it disturbs the microbiome.  And then, the second thing that we see is there are three bugs that are associated with bad unhealthy aging when they’re present in the small bowel. Again, it’s E. coli, it’s Klebsiella and higher lactobacillus growing in the small intestine. So, that’s kind of shocking to me and we’re very surprised by that. But we just published that age paper about a year ago and the disruptor paper about two years ago that lactobacillus is not good for the small bowel.  So, bifido might be okay but not lactobacillus. So, hopefully that’s a little bit helpful to your question.

Dr. Weitz:                            Steve, what’s your question? Patients have a history of SIBO, probiotic Strep if history, rheumatic fever.

Dr. Steve Wasserman:                    Yeah. Some probiotics contain Strep, Streptomyces, whatever. And if they have a history of that, I never give that because a cross-reaction especially if they had a history of rheumatic fever or bacterial endocarditis. Is there a cross-reaction with giving that strep and a probiotic?

Dr. Pimentel:                     Yeah, I don’t the answer to that question. It could be okay but I don’t know. But I see your point and I agree with you. I mean, I wouldn’t give Streptomyces. So, you’re talking about Streptomyces specifically streptococcus.

Steve:                                Correct.

Dr. Pimentel:                     Streptomyces. Yeah, exactly. Also, Streptomyces produces streptomycin which is an antibiotic and you could be allergic to streptomycin. And so if you’re taking Streptomyces and you’re allergic to streptomycin, that’s not a good thing either. So, there’s a couple of reasons why that might not be a good idea.

Carrie:                                   Thank you. And what probiotics do you like with your patients that have gotten well?

Dr. Pimentel:                     So, I think my house is turned upside down in the last three years. The reason I say that is when you do the lactobacillus studies, when you see the lactobacillus studies from the early days, it might be good for the colon. It’s not good for the small bowel. So now I’m thinking, “Okay, I have to rethink what probiotics are good or bad because they might have differential effects on the small bowel versus the colon.” And until I know, I don’t even know what I’m doing anymore.

                                                And so, I feel a little confused. I don’t feel like I want to give up on probiotics, but I need to know more because as we know more, it’s just like anything else. You don’t know what you don’t know until you know it. Sorry, that was a very twisted sentence. But we’re learning so much about all these different regions of the bowel that it’s fascinating and unraveling. It’s like we found SIFO. We weren’t sure we were going to find SIFO.  Everybody talks about Candida in the small bowel and how important it is and how it can be pathologic. But until you actually sequence, here we are, we found it. It’s true. And that’s a really important finding. We need to continue to study that.

Dr. Weitz:                          And how often did you find the Candida?

Dr. Pimentel:                     Remember, the patients who are getting endoscopy in our unit are getting it for a reason. We’re in the middle right now of doing what’s called a Healthy Control Study. Complicated because you got to take super healthy humans and scope them which is a bit of a risk. So, the IRB just finally approved that protocol for us.  So, the current REIMAGINE study has all people coming for endoscopy for a reason. So they all have some, whether they have GERD, mostly it’s GERD and other things. So, they’re symptomatic for a lot of reasons. So, about 25% of them have SIBO as it turns out. And about 3 or 4% of them, I have to get the exact number and I may get back to you but it’s roughly that, might have SIBO. So, it’s a low number but it’s not zero and it needs to be looked for. And in particular, patients who don’t respond to SIBO treatment might respond to SIFO treatment.

Dr. Weitz:                            And is there an overlap? Do most of the patients with SIFO also have SIBO or it’s a separate?

Dr. Pimentel:                     It’s often an overlap, too. So maybe the mechanisms that cause SIBO lead to SIFO in some instances or in some individuals where they’re susceptible to that fungus. So, yeah, very interesting. And some of the weird things we find in SIFO is that it’s not hyphated organisms. They’re more the yeast-type organisms. So, it’s just different. It’s fun. It’s going to be fun to continue to explore that.

Dr. Weitz:                            It’s interesting. Maybe some of the practitioners who are seeing the worst of the worst patients are seeing a higher percentage of patients who have this SIFO with SIBO. And maybe that’s why given the antifungals is helping those patients.

Dr. Pimentel:                     Absolutely. Because we’re taking a hundred patients in the REIMAGINE Study, these are from all sorts of gastroenterologists. They’re not SIFOs or SIBO specialists. So, this is all comers. In my practice where I see a lot of SIBO, the percentage could be higher, absolutely. So, you’re right. I mean, because you’re sub-selecting your population.

Dr. Weitz:                          Now, some of your research is showing a correlation with blood sugar and even artificial sweeteners with SIBO.

Dr. Pimentel:                     Right. We just presented that at DDW, big DDW for us this year. But it turns out that we found, I think the number was somewhere with 50 to 70 different organisms are changed in the small bowel because of sweeteners that are not aspartame. Aspartame is a protein but all the carbohydrate-based sweeteners, they’re the ones that change the microbiome and not always in a good way.  Aspartame hardly does anything. It’s a protein. And so, it sort of substantiates this notion that maybe you can take aspartame, but you can’t take these sorbitol, Stevia, Splenda, Splenda meaning sucralose. If you have SIBO and you take those, and I showed you, the fermentation potential, the small bowel is jacked up. And if you take sucralose, you’re going to ferment that like crazy because the E. coli and Klebsiella pneumoniae there are jacked up to ferment it as quickly as possible before anybody else does. And that’s really what’s going on I think.

Dr. Weitz:                            JoEllen asked what was the third species associated with abnormal aging? You mentioned E. coli, Klebsiella and what’s the third one?

Dr. Pimentel:                     And lactobacillus. And I’m blanking on the exact species of lactobacillus we put in that publication. But I’ll try and get that to you, Ben, the publication.

Dr. Weitz:                            Great, thanks. Are you still working on using the statins for blocking the methane?

Dr. Pimentel:                     Well, we did the first statin work and it does reduce methane. But the problem with lovastatin is it’s got this weird thing where it converts to hydroxy acid then gets absorbed. And so, we tried to formulate a version of lovastatin that would get released in specific areas of the gut.   And I guess the design was overcomplicated or what, but it reduced your cholesterol but it didn’t reduce the methane too much. So, it kind of faltered. So I think the way the formulation was made, made it even better for cholesterol but didn’t really do much for methane. So, we have to figure out a way to drop methane. And we’re working on that in the back here and we’ll have something shortly I think.

Dr. Weitz:                            Okay, excellent. I think that’s the rest of the questions. Thank you so much for your time, Dr. Pimentel. This was excellent.

Dr. Pimentel:                     I appreciate it and I appreciate all your attention and great questions. So, thank you so much.

Dr. Weitz:                            Great, thank you. And bye, everybody. We’ll see you next month.

 

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Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify and give us a five-star ratings and review. That way, more people will discover the Rational Wellness Podcast.   And I wanted to let everybody know that I do have some openings for new patients so I can see you for a functional medicine consultation for specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions or for an executive health screen, and to help you promote longevity and take a deeper dive into some of those factors that can lead to chronic diseases along the way.  And that usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing. And we’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective.  So, if you’re interested, please call my Santa Monica White Sports Chiropractic and Nutrition Office at 310-395-3111 and we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.