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Dr. Edison De Mello speaks about the Keys to Better Gut Health with 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

Dr. Edison De Mello 

Dr. Ben Weitz is available for 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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Dr. Mark Pimentel provides an Update on SIBO and IBS with Dr. Ben Weitz at the Functional Medicine Discussion Group meeting on September 23, 2021.

[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

6:52   The REIMAGINE study is the project in which Dr. Pimentel and colleagues mapped out the microbiome of the small intestine.  The Human Microbiome project was published in 2007 and they declared that they had mapped out the microbiome of the gut, but it was based on stool studies, so it did really only represented the microbiome of the colon.  [Here is the first paper published by Dr. Pimentel and others on this REIMAGINE study:  Mapping the Segmental Microbiomes in the Human Small Bowel in Comparison with Stool: A REIMAGINE Study.]  This study required a lot of work and resources to be able to collect accurate samples and sequence the microbiome of the small intestine.  It is difficult the sequence the small intestine for a number of reasons, including that the mucous is so thick that they had to add mucolytics to liberate the bacteria and they had to develop special tools and validate them before conducting the trial, so it took years to prepare the conduct it.  And they discovered that the microbiome of the small intestine is quite different from the colon.  They also discovered that the small bowel is fairly uniform from the duodenum till the end of the ileum, whereas it was thought previously that you had more and more bacteria as you get closer to the colon.

9:28   Now we know that the bacteria in the small intestine have not overgrown from the colon up into the small intestine through an incompetent iliocecal valve, as was previously believed by some SIBO researchers. The small bowel contains more proteobacteria and much less bacteroidetes than the colon.  What happens in SIBO is that because of damage to the motility of the intestine, E. coli and Klebsiella grow like weeds and crowd out many of the other commensal bacteria.

12:13  Ehler’s Danlos Syndrome (EDS).  There was a thought that patients with EDS who have ligamentous laxity have hyperlaxity of the ileocecal valve leading to an increased risk of SIBO.  Dr. Pimentel explained that what happens with patients with EDS is that they have visceroptosis, which means that their gut sags into their pelvis, which creates bends and twists in their small bowel, creating obstruction, leading to SIBO.

13:48  Dr. Pimentel’s group published data from the REIMAGINE trial that shows that PPIs (proton pump inhibitors like Prilosec) don’t cause SIBO, though they are a risk factor for C. diff colitis.  They also published a paper showing that in postmenopausal women, their microbiome gets shifted in a very bad way, but if they’re on hormone replacement therapy, their microbiome in their small intestine looks like they’re premenopausal.

15:24  This data that PPIs don’t cause SIBO means that taking PPIs will not likely affect the results of the SIBO breath test.  On the other hand, PPIs by reducing stomach acid will reduce methane production, since methanogens feed on hydrogen that is contributed by hydrochloric acid.  You should stop probiotics for about a week before taking the test.  Patients should not take laxatives within 24 hours of taking the SIBO breath test. This also goes for herbal laxatives and magnesium. Patients should also stop antibiotics and antimicrobial herbs prior to taking the test. On the other hand, if the patient is still bloated with whatever they are taking, then we can conclude that it’s not working and likely will not affect the test result.

23:00  About 25% of those who have a flat line on a two breath test, which we previously diagnosed as being positive for hydrogen sulfide SIBO, are positive for hydrogen sulfide on the three breath test.

23:50  The organisms that cause hydrogen sulfide SIBO is more complicated than those that cause methane SIBO. With methane SIBO we have Methanobrevibacter smithii, Methanobrevibacter stadmenii and then a couple of other minor methanogens, and we’ve actually shown that M. smithii correlates with constipation, correlates with the methane on the breath test, and so forth.  Dr. Pimentel said they have shown that M. smithii correlates with constipation, correlates with the methane on the breath test, and so forth.  In the case of hydrogen sulfide, though, there’s multiple organisms that can produce hydrogen sulfide, including pseudomonas, Fusobacterium, Desulfovibrio, and Bilophila.

26:16  Dr. Steven Sandberg-Lewis, who spoke at our meeting a couple of months ago, he said that he’s been finding a number of patients with hydrogen sulfide SIBO positive with constipation.  Any time you have a patient that does not fit the pattern, such as a patient who is positive for hydrogen sulfide SIBO who has constipation, Dr. Pimentel recommended that you work them up with a colonoscopy or a CT scan to see if they have a tumor or a blockage in their colon.

27:49  Treatment for hydrogen sulfide SIBO often includes bismuth, which dates to a study from 1998 from a gastroenterologist, Michael Levitt, who wrote an article in the New England Journal of Medicine about flatus and how bismuth inhibits sulfate reduction pathways, thus reducing gas production.

29:24  Biofilms.  Some of the microorganisms that cause SIBO, like Methanobrevibacter, reside in the mucous layer, which is essentially a biofilm, so busting this mucous layer a bit may be helpful in erradicating them and maybe bismuth is helping with this.

30:54  Hydrogen SIBO.  The organisms that cause hydrogen SIBO are mainly E. coli and Klebsiella and sometimes Aeromonas. 

32:10  Methane SIBO.  Dr. Pimentel explained that they will be publishing how many methanogens are found along the small intestine in different sections, as well as in the stool. In terms of treatment, he recommends rifaximin and neomycin based on the double blind study, rifaximin with metronidazole as a substitute. He also finds Allicin to work well and he also still likes lovastatin, and the veterinary literature is strong, but the problem is that it gets absorbed, so he is still working on a formulation that will not get absorbed.

33:23  While the type of E. coli that causes hydrogen SIBO is not the pathogenic, E. coli that has the gene for CdtB endotoxin, there are still lipopolysacharides that other chemicals that may be getting released that can cause inflammation and pain.

37:02  Dr. Sam Rahbar is an integrative gastroenterologist in LA and he’s recently published on some patients who have tick-borne illness such as Lyme disease and it often seems to be correlated with patients with methane SIBO or IMO.  Dr. Pimentel said that they have not analyzed the genetic material that they found to look for spirochetes or other parasites yet.  Dr. Pimentel also said that he agrees that sometimes fungal overgrowth (SIFO) is a factor in IBS, but it is not as common as bacterial SIBO and he refers to Dr. Satish Rao, who is part of his research group, who has done more work on fungal overgrowth. 

39:48  Are elevated levels of Methanobrevibacter on a stool test indicative of IMO?   Yes, as long as the levels are above 10 to the 4 and they are associated with constipation. 

41:06  Lovastatin has been used successfully by some doctors off label for IMO at a dosage of 30 mg at bedtime.

42:24  Some doctors have suggested using 120 minutes as the cutoff time for evaluating a breath test instead of 90 minutes for patients with slow motility, such as those with constipation, but the problem is that if the patient has gastroparesis or is a narcotic user, you don’t know what their transit time is and even 120 minutes may not be enough.

43:26  Mycotoxins.  

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 100 scientific papers and he 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 nutrition consultations, including remote consults via video or phone, 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, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or go to www.drweitz.com. Phone or video consulting with Dr. Weitz is available.

Podcast Transcript

Dr. Weitz:                            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading and nutrition experts and researchers in the field to bring you the latest and 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.

Welcome, everyone, and thank you for joining our functional medicine discussion group meeting tonight, and we’re very excited to have Dr. Mark Pimentel joining us for a discussion on the latest updates on small intestinal bacterial overgrowth and irritable bowel syndrome.  I’m Dr. Ben Weitz. If you have any questions, please type them into the chat box and I’ll either call on you or ask Dr. Pimentel when it’s appropriate. If you’re not aware, we have a close Facebook page, The Functional Medicine Discussion Group of Santa Monica. I’m recording this event, and I’ll post it on my YouTube page, and I’ll also include it in my weekly Rational Wellness Podcast.  If you’ve not listened to it, please check out the Rational Wellness Podcast, subscribe on Apple Podcast or wherever you listen to podcasts. If you joined, please go to Apple Podcast and give us a ratings and review.

We have two sponsors for this evening, Integrative Therapeutics and Vibrant America Testing. I know that the representative from Vibrant is here. So go ahead and tell us a little bit about Vibrant America Testing.

Margot:                                Hi. My name is Margot. I work at Vibrant America in Los Angeles. We work with Dr. Ben Weitz. So Vibrant is a CAP and CLIA-certified full service lab in Northern California with everything from basic blood panels to autoimmune diagnostics. So today, I wanted to bring up one of our most popular panels. It’s the Total Tox-Burden. It includes 31 mycotoxins, 20 heavy metals plus 39 environmental toxins all for under $400. So if you guys are interested in learning more, please email me at margot.h@vibrant-america.com or you can check out our website at www.vibrant-america.com.

Dr. Weitz:                            Okay. Thank you. It looks like Steve Snyder is not here. So let me tell you something about Integrative Therapeutics. They’re one of the few professional manufacturers of high quality nutritional supplements that we carry in our office. They’re sold through practitioners. They have some great products for SIBO. They have the leading brand of the elemental diet, and they have it in the dextrose and non-dextrose version. That’s one of the treatments for SIBO. If you’re not aware of the elemental diet, you should definitely find out more about it. You can talk to Steve Snyder from Integrative Therapeutics.  They also have a great natural pro-kinetic motility activator, which is a really excellent product and we use that all the time. So I want to thank Integrative Therapeutics and Vibrant America very much for helping sponsor tonight’s podcast, tonight’s functional medicine meeting.

Now, I want to introduce Dr. Mark Pimentel, who’s head of the Pimentel Lab, an executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. Dr. Pimentel really needs no introduction, but he is a prolific researcher having published over 150 scientific papers. His lab researches the microbiome and the irritable bowel syndrome. As most of us know, irritable bowel syndrome is probably the most common gastrointestinal condition affecting between 10% and 15% of people in the United States and around the world.  For many years, prior to Dr. Pimentel’s research, IBS was thought to be a diagnosis of exclusion. Once inflammatory bowel disorders, Celiac disease, parasites, and all the conditions that could be diagnosed with a stool sample or looking through a scope, you are then left with IBS. IBS was and still is seen by an unfortunate number of gastroenterologists as a condition of either unknown cause or caused by stress or anxiety. In fact, antidepressants were once one of the most popular medications to treat IBS.  Dr. Pimentel is the first researcher to demonstrate that small intestinal bacterial overgrowth is a cause of IBS in the majority of cases, and that SIBO could be diagnosed with a lactulose breath test. Dr. Pimentel also pioneered the use of rifaximin, a non-absorbed antibiotic as a treatment for IBS. He’s developed an autoimmune model of IBS being caused by an episode of acute gastroenteritis. He’s developed a blood test looking at antibodies vinculin and cytolethal distending toxin to diagnose this autoimmune cause of IBS.  He’s discovered that the methane-producing organism, Methanobrevibacter, causes constipation. Dr. Pimentel and colleagues have recently renamed the methane version of SIBO as IMO, which stands for intestinal methanogen overgrowth. Most recently with his REIMAGINE study, Dr. Pimentel for the first time ever has mapped out the microbiome of the small intestine, which is a monumental achievement.  Most importantly, Dr. Pimentel has given hope to millions of patients with IBS that they might be able to feel better and stay better. So thank you, Dr. Pimentel, and thank you for joining us tonight.

Dr. Pimentel:                     It’s my pleasure. Thank you for inviting me.

Dr. Weitz:                          Absolutely. So how do you want to start?

Dr. Pimentel:                     Well, you tell me. You usually do an interview? Is that what you’re hoping to do tonight?

Dr. Weitz:                          Sure. Absolutely. That’s just fine.

Dr. Pimentel:                     I got to tell you, you always ask the best questions. So I love this podcast for that reason. You’re always well-prepared.

Dr. Weitz:                          Exactly. Well, thank you, thank you. So let’s start off with your mapping out the microbiome of the small intestine. Why don’t you tell us about how you were able to do that and what’s some of the latest information that you’ve gotten out of that?

Dr. Pimentel:                     Well, the human small intestine, what I’d like to say is that the Human Microbiome Project was published in 2007. One of their declarations was, “Well, we published the Human Microbiome and this is what the gut represents based on stool studies.” I was always shocked by that because I felt like, well, stool is stool, but what about the small intestine? What about other parts of the gut? Maybe it’s different. It took us a decade to start to get our act together in terms of getting the REIMAGINE study off the ground because we needed a lot of resources and some of the sequencing equipment. Now, we’ve got everything here at the MAST program.  The problem with the small intestine is it’s not easy to sequence. The mucous is too think. So we realized you couldn’t do what you do with stool. You couldn’t process the stool the same way or the small bowel the same way as stool, and we have to add mucolytics and other things to liberate the bacteria before you get their DNA, but we did all that. We’ve published validations of how you’re supposed to handle the small intestinal microbiome.

While we found a ton of stuff since starting, we found bacteria that produce all sorts of things that humans produce manipulating the human body, and you’re going to see some of that. There’s a paper, again, September, sorry. Ben, I can’t tell you things, but next week there’s a paper coming out. I feel like I’m teasing you too much, but there’s a paper coming out that is the next iteration.  Your point was last year we published and made the cover of the journal what the small bowel looks like. The small bowel is completely different than the colon. A couple of pearls. It’s interesting. The duodenum, jejunum, the ileum, they look identical. We used to think, “Oh, the closer you get to the colon, the more dirty it is, the more colonic it looks like.” It wasn’t what we saw. It was, literally, duodenum, jejunum, ileum looked the same. Then it’s like a cliff. The microbiome completely changes once you hit the colon. I think that’s really so poignant. We have other pearls like people don’t-

Dr. Weitz:                          Can’t I ask you a question about that fact?

Dr. Pimentel:                     I’ll do it for that one.

Dr. Weitz:                          So I want to get right back to it, but does the fact that the level of bacteria you’ve seen throughout the small intestine, does that tell us anything about whether the bacterial overgrowth comes from below up or from above down? In other words, we originally were thinking that the bacteria from the colon were overgrowing into the small intestine. Does the fact that there’s not more bacteria at the distal part of the ileum, does that indicate that that’s not the case?

Dr. Pimentel:                     So all of this notion, believe me I’m guilty of saying the same thing, all of this notion that overgrowth is the colon bacteria coming up into the small intestine is from older data that says, “Well, if the ileocecal valve is incompetent then the stool is reflexing into the small bowel and that contaminates the small bowel,” but as the REIMAGINE study is telling us, that’s not exactly how it happens.  What happens is the small bowel contains generally more proteobacteria than the colon. The small bowel contains no bacteroidetes, hardly at all, but that’s half of what’s the colon. So it’s the composition that’s different, but what we find with SIBO, in sequencing I mean, is that there’s weeds that develop, E. coli and Klebsiella. When they start growing because the flow of the small bowel is not correct, then you get SIBO. E. coli and Klebsiella are just rampant. They run up like weeds and then they crush everything else around them. So it’s not really that the colon bacteria are coming up. It’s that E. coli and Klebsiella are taking the opportunity to become those weeds that they want to be.

Dr. Weitz:                          Is this largely because of decreased motility? We still think that’s one of the main factors?

Dr. Pimentel:                     Yeah, decreased motility. One of the slides I finally added to my new slide deck is there’s a paper that came up because people were saying, “Well, you say, Dr. Pimentel, that adhesions slow motility and maybe you get SIBO from adhesions, but where is the paper that’s published that shows this?”  Well, a paper just came out with sequencing the small bowel, again, in patients with partial bowel obstructions, and sure enough, it’s E. coli, it’s proteobacteria, and so SIBO in that. The point of that paper is anything that slows the gut down, we are correct, it does generate SIBO and allows these E. coli and Klebsiella to take the opportunity to be the weeds.

Dr. Weitz:                            So along the same lines, we sometimes see patients with Ehlers-Danlos syndrome and they have a higher incidence of SIBO, and we would think now it was because of laxity, maybe, in the ileocecal valve. I wonder why patients with that condition looking at hyperlaxity would have an increased risk of SIBO if it’s not coming up from below.

Dr. Pimentel:                     Yeah. So I mean we published one paper on EDS where we’re looking at visceroptosis. So I don’t know if you know the term visceroptosis, but it means that the gut is sagging into the pelvis, and by doing so, it creates all sorts of bends and twists in the small bowel. So I think physically, it creates impairment like your hose bent in the garden and the water doesn’t flow through it. I think that’s what’s going on is just everything is crushed on top of each other down on the pelvis.  That’s a characteristic sign. So the way you do a visceroptosis is you give the barium, you get them to stand up and take a picture front and all the bowel should be nice all over the place, but in the Ehlers-Danlos, it’s all flat down on the pelvis. It’s sad to see it because it’s not a pleasant thing to have for the future for that patient.

Dr. Weitz:                            Okay. If you want to continue on your telling us about some of the findings from the REIMAGINE study.

Dr. Pimentel:                     This is what I get excited about every day. Well, what I was going to tell you is that one of the other things we published, so not everything is in September and I can’t talk about it, but we did publish that PPIs, proton-pump inhibitors, don’t cause SIBO. The sequencing data does not support that, but PPIs do do something really interesting. They reduce clostridial species in the gut. You probably know this, Ben, but PPI is a risk factor for C. diff colitis.  So it’s like you have this neighborhood that’s supposed to be full of clostridium but for some reason, PPIs make those clostridia go away, but that gives an opportunity for some houses to be support another type of clostridia that isn’t good and that might be C. diff. So anytime you leave an opening, other organisms take the opportunity to come in there and take over. So maybe that’s why C. diff grabs hold in these PPI-treated patients. So there’s that paper.

We showed in another study presented at DDW that women who are postmenopausal, if you look at their small bowel, postmenopausal women, their microbiome gets shifted in a very bad way, but if they’re on hormone replacement therapy, their microbiome in the small bowel looks just like they’re premenopausal.  So it’s stuff like that that we’re finding. Again, another paper next week that will get some press, I think, that’s going to be another impactful paper on just getting the knots and bolts of what’s going on in the microbiome.

Dr. Weitz:                            So you mentioned PPIs don’t affect SIBO. That brings up, I’ll jump to a question, which I wanted to ask you about. How important are the pretest procedures before somebody gets a breath test and what are the recommendations? Does that patient stop taking PPIs? Does that mean that’s no longer important?

Dr. Pimentel:                     Well, this paper suggests you shouldn’t have to worry about it. So now, there’s a caveat to that. Patients with methane, for example, when you reduce acid in the stomach, you’ll reduce methane production. We showed that in another paper. We don’t see a lot of methanogens in the upper duodenum. So we can’t actually see that methanogens are being affected by PPI in that PPI study. So there’s reasons for not being on PPI, but to be honest with you, I don’t think PPIs do much to the breath. That consensus was three years ago, so we didn’t have the luxury of that data at the time.

Dr. Weitz:                           Interesting. So does that mean possibly for functional medicine practitioners supplementing with hydrochloric acid for patients with methane SIBO or IMO might be beneficial?

Dr. Pimentel:                     The opposite because methanogens can use hydrogen of any sorts.

Dr. Weitz:                           Okay. Okay. Okay. Okay.

Dr. Pimentel:                     Yeah. So it’s possible that you could be making or putting more gas on the fire with acid.

Dr. Weitz:                           Okay. Yeah, yeah, yeah. So since I asked the question about pretest procedures, what other pretest procedures do you think are most important to get an accurate result and what things need to be stopped over what period of time? How about probiotics?

Dr. Pimentel:                     Yeah. I think most probiotics that you take don’t produce hydrogen, but we generally recommend not beyond those for about a week before the test. Where we get into trouble, and this is a question I got earlier today on another call is, “What about my constipated patient taking laxatives, “Are you telling me I can’t take a laxative for a week before the breath test? I’ll die,” because it’s really hard for these patients.  The North American consensus is meant to be a rule of thumb. It’s not meant to be a gospel, but it is true that I have patients where they come in, I was sure they had SIBO, they do the breath test, it’s negative, and then I talk to them and they say, “Yeah, I had a massive diarrhea the morning of the breath test just before I came to the office to do the breath test because I took all my laxatives last night.”  So if you flush the gut, you’re going to have a negative breath test and that screws up the test, obviously. So you just got to be careful in some of these patients with constipation that they didn’t just take a monster amount of laxatives the night before because they were worried about how bloated they get with the breath test.

Dr. Weitz:                          Okay. So they’re supposed to stop laxatives.  What about herbal laxatives?  What about magnesium and vitamin C? Is that the same thing?

Dr. Pimentel:                     Vitamin C, not as much, but, yeah, herbal laxatives, I mean, anything that’s going to cause you to be purging within 24 hours of the test can have an influence, for sure.

Dr. Weitz:                          Including magnesium citrate.

Dr. Pimentel:                     Yes. Yes. Absolutely.

Dr. Weitz:                          What about herbal antimicrobials?

Dr. Pimentel:                     Yeah. Well, any herbal antimicrobials are antimicrobials, but the way I deal with that is, for example, if a patient says, “I’m still bloated with whatever I’m taking,” then they’re still bloated with whatever they’re taking.  A, it’s not working and B, they must have SIBO.  So it shouldn’t affect. Then the other thing is a lot of times patients will do a breath test after antibiotics to make sure it’s gone.  So I have no problem.  You don’t have to wait a month to do a second breath test.

Dr. Weitz:                          Now, has the new Trio breath test, which measures all three gases, has that recently been recalibrated so that fewer patients would test positive?

Dr. Pimentel:                     So the new breath test is the sensors are supposed to be more accurate down to 0.1 or 0.2 parts per million. If you look at the readings and how it’s reported, you don’t just get 49, you get 49 point something because the sensors are certified to be sensitive to that level, not that you need that extra sensitivity, but the bag system is designed to retain all the gases very well and it’s validated that those bags filled with your air, your lung air, can last a week and hold hydrogen sulfide, methane, and hydrogen correctly as it was on day zero.  So that’s all certified by the CLIA Lab. So in that sense, you’re getting a more accurate result.  Also, the CO2 tends to be higher than other testing because of the way the system works.  So it’s a closer to true alveolar gas and, therefore, you could say you don’t have to adjust the gas.  The biggest problem with breath testing is when you get a bad sample and you get a low CO2 and you have to … So what you do is you correct the CO2 up to 5.5. If you have to correct it from one to 5.5, then you got to multiply every number by five and a half. The more you correct, the more error you impose on the breath test. So it’s important that you get good samples.

Dr. Weitz:                          Has the test been changed? In other words, were they getting too many positives and did they have to change the calibration of the test?

Dr. Pimentel:                     I don’t know.  For hydrogen, methane, hydrogen sulfide?

Dr. Weitz:                          No, for hydrogen sulfide, yeah.

Dr. Pimentel:                     Well, no.  So hydrogen sulfide, okay.  So I understand your question now. I’m sorry.

Dr. Weitz:                          Yes.

Dr. Pimentel:                     So hydrogen sulfide, so when we did our first validation of hydrogen sulfide, we selected functional chronic diarrhea patients. The functional chronic diarrhea patients were finding that their hydrogen sulfide was over five parts per million compared to constipation, compared to healthy.  Just recently, and this has not been published, but it’s been used for validation of the test. We completed a group of D-IBS patients. So you have D-IBS and then the diarrhea patients who are functional diarrhea. So they’re more severe. They’re having diarrhea every single day. Whereas DIBS is on again off again diarrhea. The DIBS is almost often over three parts per million. So now that we have that data, it drives a change in what we think is positive, so anything over three now because constipation is almost always less than three. So as data come in, the science dictates how you interpret the test. It’s the same thing as … Sorry. Was somebody asking?

Dr. Weitz:                          No. I just didn’t mute them as they were coming in.

Dr. Pimentel:                     Okay.

Dr. Weitz:                          Okay. Let’s see. What was the question? Have you gone back and seen if patients who got a flat line on the two breath tests, does that correlate with a positive result for hydrogen sulfide on the three breath test?

Dr. Pimentel:                     Yes. We’ve shown that up to a quarter of patients. Up to a quarter of patients are testing positive for hydrogen sulfide in general, and we’ve seen that, but what I mean is up to a quarter of patients with flat line are testing for hydrogen sulfide. There are still some flat liners that could be unexplained as either poor transit, gastroparesis, maybe even bowel. There’s many reasons why you could have a flat line besides hydrogen sulfide, but, yeah, about a quarter of patients are hydrogen sulfide.

Dr. Weitz:                            Can you talk about the organism Fusobacterium varium that you have found to be … This is a question that Alison asked me to ask you. That appears to be linked with causing hydrogen sulfide SIBO.

Dr. Pimentel:                     Yeah. Thanks, Allison for that question.  So the methane story is simpler.  The methane story is you have a couple of methanogens, Methanobrevibacter smithii, Methanobrevibacter stadmenii and then a couple of other minor methanogens, but we’ve actually shown that M. smithii correlates with constipation, correlates with the methane on the breath test, and so forth.  In the case of hydrogen sulfide, though, there’s multiple organisms that can produce hydrogen sulfide. For example, pseudomonas can produce hydrogen sulfide.  Fusobacteria can produce hydrogen sulfide.  Desulfovibrio can produce hydrogen sulfide, and there’s Bilophila can produce hydrogen sulfide.  So there’s a little bit of a laundry list of hydrogen sulfide producers.  I think Allison is referring to a study we did where we took Fusobacterium and we gavaged or inserted it into the bowel of rats in a rat study.  The purpose for this study was to show putting a bacteria that makes a lot of hydrogen sulfide, will in the animal create the animal to produce hydrogen sulfide and we can detect it.  So we were able to detect an increase in the animal’s production of hydrogen sulfide in their body.  The second part of it is as they grew this Fuso in their body and produced hydrogen sulfide, the animal started to have diarrhea, but then the animal, because this organism wasn’t natural to them, eventually cleared the organism.  The hydrogen sulfide resolved. The diarrhea resolved.  So it’s essentially trying to fulfill Koch’s postulates of cause and effect.  An organism that produces hydrogen sulfide, you put it in, it produces hydrogen sulfide, you get the diarrhea, the organism goes away, the hydrogen sulfide goes down, the diarrhea goes away.  So we’re just trying to prove the point that hydrogen sulfide production causes diarrhea.

Dr. Weitz:                          Now, Dr. Steven Sandberg-Lewis, who spoke at our meeting a couple of months ago, he said that he’s been finding a number of patients with hydrogen sulfide SIBO positive with constipation.

Dr. Pimentel:                     So anything we do has an overlap. There’s no black and whites in medicine. So if you were to look at our graph with a dot plot, you have patients who are constipated, for example, that have, and I could show a graph, but there are occasional constipation patients where their hydrogen sulfide is high and we don’t understand why, but just remember this that if I put a blockage in my colon, let’s say I had a tumor in my colon, and the bowel is obstructed. I would be constipated, and then bacteria in the colon would build up. If you happen to have sulfate-reducing bacteria and they build up, you’d get hydrogen sulfide, but you’re constipated because you have a tumor in your colon.  So anytime in my practice when I see something that doesn’t fit, outliers like that, I go to further workup to be honest, something doesn’t fit, because 90% of people with hydrogen sulfide don’t have constipation. So if I see a constipator, I’m going to work them up further, maybe a colonoscopy, maybe other things.  So these are all clues to something else possibly affecting them.

Dr. Weitz:                          So what do we know about, since we’ve been talking about hydrogen sulfide SIBO, what do we know about treatment for hydrogen sulfide SIBO? I noticed that you tend to use bismuth as part of your protocol and I’ve talked to a number of functional medicine practitioners who also use some form of bismuth. Why do you think bismuth might be helpful?

Dr. Pimentel:                     Well, it was a study from 1998 from a guy, Michael Levitt. I don’t know if you’re familiar with him, but he was a gastroenterologist in the ’70s, ’80s, and ’90s, and he has a New England Journal of Medicine article on flatus. If you can imagine a bunch of flatus article on New England Journal now unless COVID causes flatus, then you’ll get that published.

Dr. Weitz:                            … or if vitamin D causes flatus then that would get published, too.

Dr. Pimentel:                     Yeah, but to be honest, what he was studying was intestinal gas production and it was seminal work at its time. He actually described what he thought was the mechanism is that it inhibits sulfate reduction pathways within the organism and then that reduces their energy and they can die from that. So it was paper of 1998 that I use in my presentation that describes that, but, yeah. I mean, this is all we got to go on at the moment, but stay tuned for more studies that are coming.

Dr. Weitz:                          So here’s some speculation. I think that there’s some data to show that bismuth may be helpful in breaking up biofilms. Have you, in looking at the bacteria in the small intestine and SIBO, have you seen biofilms present and do you think that might be a factor when we treat SIBO?

Dr. Pimentel:                     Yeah. So I mean, the difficulty with biofilms is the way we see it in the REIMAGINE study is you’ve got a layer of thin liquid right on top, then you’ve got mucous, and then when you biopsy the mucosa in between the villi, there’s another layer of mucous. So there’s various biofilms, and each of those layers has a different microbial composition, but we see some of those organisms in the deeper layer.  So, for example, Methanobrevibacter loves the mucosa. So we don’t see a lot of the Methanobrevibacter up in those higher layers of the liquid layers, but busting the biofilm or the mucous can help you in treating some of these patients. So maybe bismuth is working by busting up the mucous and helping you get at these organisms, but we haven’t layered out H2S yet. So I can’t give you an honest answer as to where H2S organisms are residing most commonly.

Dr. Weitz:                          So let’s go to hydrogen SIBO. Which organisms are primarily involved with hydrogen SIBO?

Dr. Pimentel:                     Oh, this we know a lot about. So the REIMAGINE study, we did publish last year a very important paper and we’ve had these debates on these calls as well previously, but E. coli and Klebsiella, those are the two weeds in the garden, but we also showed that the breath test correlated with all the sequencing, and that the hydrogen production pathways are increased in the small intestine of patients with hydrogen SIBO because of the E. coli and Klebsiella.  The reason that’s important is because there are people who said, “Oh, the hydrogen is coming from the colon. It’s coming from colon bacteria and lactulose getting to the colon.” What that paper showed was that that’s not the case. This is happening in the small intestine, and it’s E. coli and Klebsiella. You remember those two, and a little bit of Aeromonas, which I’ll sprinkle in there because we do see a little Aeromonas going up as well.

Dr. Weitz:                            What was I just going to say? I can’t remember what I was just going to say. So I had a thought there. So when it comes to methane SIBO or now it’s called IMO, what’s the latest? What have we learned from the REIMAGINE study on that?

Dr. Pimentel:                     Yeah. So the one thing we’re going to be presenting or submitting to DDW in December is now what we’re doing is we’re mapping intestinal methanogens along the entire intestine. So we’ll show you how much is in the duodenum, the jejunum, the ileum, and then subsequently in stool, and we’ll be able to map it out. In terms of treating IMO, things haven’t changed all that much. We still give rifaximin and neomycin based on the double blind study, rifaximin with metronidazole as a substitute.  Obviously, there’s no FDA-approved drug for IMO because it doesn’t work that way, but that’s what the data and the literature supports at the moment. There are other treatments. Allicin is another product from garlic that seems to work well with reducing methane. We still like lovastatin. Lovastatin, the data in the veterinary literature is very good, but it’s tricky with lovastatin because it gets absorbed.

Dr. Weitz:                            Oh, I know what my question was now with the hydrogen. So do you think that E. coli can produce endotoxins? We know endotoxins are produced by Campylobacter with food poisoning that can often be the cause of SIBO to start with. Do you think that endotoxins secreted by the bacteria that cause hydrogen SIBO or the other forms of SIBO are playing a role in some of the pain and symptoms patients are experiencing?

Dr. Pimentel:                     Yeah. So okay, first of all, hydrogen is something we’ve looked at for years. Hydrogen, no matter how high it is, doesn’t predict the severity of the symptom, whereas hydrogen sulfide does. So the higher it is, the more diarrhea you have, the more pain you have and the more urgency you have, but in terms of the toxin, I think you’re referring to the CdtB toxin.

Dr. Weitz:                          Yeah.

Dr. Pimentel:                     E. coli, pathogenic E. coli has that gene for CdtB, but native E. coli to the gut, which is what’s producing the SIBO, it generally doesn’t. It’s not a pathogen. It’s more of a colonizer, and now it’s blooming, and that’s what’s causing the SIBO, but Campylobacter definitely has CdtB and that’s what triggers your antibody production, CdtB antibody, and then the anti-vinculin antibody, which is the blood test for IBS.

Dr. Weitz:                          Okay. So we don’t think that endotoxins is playing a role other than the endotoxins from Campylobacter that leads to the autoimmune reaction.

Dr. Pimentel:                     I wouldn’t say it that way. I mean, I think I know where you’re going with this, but, for example, E. coli has lipopolysaccharides and other things, other wall chemicals that don’t make you very happy. So having all that E. coli and Klebsiella around does create a bit of an inflammatory response, we think, and in addition to the hydrogen and all these gas dynamics that we’ve been talking about for the last little while.  What lipopolysaccharides or these endotoxins are doing exactly is unclear. Again, we have a study that we just finished. It’s a very large animal study and we see a lot of effect of these endotoxins on the cytokines in this animal, but, again, I can’t really talk about it at the moment, but you’ll see some of that data in a few months.

Dr. Weitz:                            Somebody asked a question about the biofilms. So in the functional medicine world, there are various compounds, nutritional compounds that we’ll use to try to break up biofilms, and some of them are enzymes. There are some products that use a combination of bismuth with some other substances. If we were to use agents that we think might help break up biofilms, would that be something that we would do prior to using antimicrobials or at the same time or what would you think would be the timing of the use of that protocol?

Dr. Pimentel:                     I think some of the data we have that’s published on E. coli is that a lot of these E. coli and Klebsiella are swimming through the mucous. So breaking up the mucous is something we’re very interested in in terms of trying to improve our treatments.

Dr. Weitz:                            Okay. Okay. Good. So let’s go back to IMO. So Dr. Sam Rahbar is an integrative gastroenterologist in LA and he’s recently published on some patients who have tick-borne illness such as Lyme disease and it often seems to be correlated with patients with methane SIBO or IMO. I wonder in your research, have you seen any evidence of spirochetes or other parasites in the small bowel?

Dr. Pimentel:                     So the REIMAGINE study, we have the genetic material from the small bowel. We haven’t actually done this. You have to take the sequences and throw it in a database that looks at parasites or fungi or other things. So we haven’t don’t the parasites yet, but, I mean, there’s data from Sweden and other countries in Europe on the role of spirochetes, for example, in IBS specifically, and they’re finding increased spirochetes in the colon, but the connection to IMO, I don’t have any data for that yet. I’d be curious to see exactly what the data looks like from Dr. Rahbar.

Dr. Weitz:                          Okay. A lot of us have found that the methane SIBO or the IMO is more difficult than hydrogen SIBO, and a lot of times when the patients don’t resolve, we try using different antimicrobials. We look for other possibilities. I think Dr. Rahbar has also spoken at the fact that sometimes he’ll see fungal overgrowth. So the question for you is in your data, did you see candida or other fungus in the small bowel related to IMO?

Dr. Pimentel:                     I think Satish Rao is the ultimate expert on this from Georgia. He’s published a lot of the work on this, but we do see fungal overgrowth occasionally, maybe a handful of times a year in my practice. Dr. Rezaie sees it in some of his refractory patients also. So where he thinks it’s overgrowth or bloating, he treats them, they’re not getting better, and then uses an antifungal and it seems to be effective. He’s also cultured candida in some of these patients as either part of the REIMAGINE study or through the clinical lab and then treated them. So it’s definitely there. It’s definitely present in some of these patients, but I would say it’s not as common as the bacterial SIBO, for sure.

Dr. Weitz:                          Okay. Since IMO occurs throughout the entire digestive tract not just in the small intestine, right?

Dr. Pimentel:                     Right.

Dr. Weitz:                          So would elevated levels of Methanobrevibacter on a stool test could just possibly be indicative of IMO?

Dr. Pimentel:                     So Methanobrevibacter smithii in a stool test, if you go back to a paper we’ve published now a number of years ago, 10 to the four, up to 10 to the four or 10,000 smithii per milliliter is considered physiologic, meaning you don’t have any symptoms, you don’t have constipation, but anybody over 10 to the four was constipated. Anybody over 10 to the six then you start to see it in the breath.  So, yeah, there is some merit to doing stool M. smithii, but you have to use that trial, but we’re getting better at evaluating M. smithii in the stool using QPCR and some of the new refinements are going to have some surprising results, but the point I’m trying to make is, if you see M. smithii in the stool, often that’s normal as long as it’s very low in number.  So you just have to be careful how you interpret those stool tests.

Dr. Weitz:                          Okay. Somebody asked a question about using lovastatin. It sounds like she’s considering possibly using lovastatin.

Dr. Pimentel:                     Yeah. I mean, the dose we use for lovastatin, again, it’s an off label use, is 30 mg at bedtime, and we do see methane reduction, but it’s a little bit, it’s challenging because if you just use plain old lovastatin, there’s always a risk of muscle aches and other side effects of lovastatin.

Dr. Weitz:                          I’m not sure where that echo is coming from. Have you looked into the use of red yeast rice as a possible alternative?

Dr. Pimentel:                     I haven’t personally used it, but I know some people who have and have gotten some decent responses from it because red rice yeast does have lovastatin, natural lovastatin in it.  So that could be effective.

Dr. Weitz:                          Yeah. There’s actually products on the market that we tend to use that make sure that there’s no lovastatin, but they seem to have the same effect, and we see much lower side effects of muscle problems using it versus statins.  So for patients with slow motility such as those with constipation, should we consider a cutoff of 120 minutes instead of 90 minutes for interpreting a positive test?

Dr. Pimentel:                     Yeah. The problem is you don’t know who and what they have. So, for example, there are patients who might have diabetes for a few years and for all intents and purposes they just have bloating. You do the test and they have gastroparesis and you see a flat line because the lactulose or glucose never left the stomach. So it’s those things that create trouble because you don’t know they have gastroparesis and then you get a flat line test, but waiting 120 minutes, waiting three hours, you don’t know how long to wait for each of those individuals because you don’t know what their transit is. Narcotic users have the same issue.

Dr. Weitz:                          Okay. A number of us in the functional medicine world who have difficult to treat IBS slash SIBO patients sometimes will look at the possibility of mycotoxins or exposure to mold and we have found a certain amount of benefit from this pursuit and have had, I know personally have had a number of patients with difficult to treat SIBO who got better after we looked at the possibility of mycotoxins, found that they had some exposure to mold. Do you think that there might be in some way that SIBO might make patients more likely to experience either be more sensitive or to experience symptoms with exposure of mycotoxins?

Dr. Pimentel:                     Yeah. So I mean, my understanding of the literature of mycotoxins is very limited, so I’m going to have a very muted response to that because I don’t know enough about it, but what we are seeing and Mike Camilleri from the Mayo Clinic just is publishing a paper now where there is increased intestinal permeability in some of these patients and in IBS patients.  So the worry is that you have some increased permeability to whether it’s food, food allergies, food antigens. There’s another nature paper that came out of Europe saying that patients with IBS, for example, are more susceptible to allergens maybe because the tight junctions are more open.  So as we start to see maybe the anti-vinculin antibody is allowing these tight junctions to be more open, all of that work needs to still be done, but the pieces are coming in to place. We just don’t have all the answers yet.

Dr. Weitz:                          What about the relationship between IBS and IBD, inflammatory bowel disorder?  I know I’ve seen patients with IBD who also had IBS, and when we treated the IBS, their IBD improved.  What do you think might be the relationship?

Dr. Pimentel:                     I’ve had an on and off relationship with IBD in the sense that there was a period of time where I thought IBS may be a precursor to IBD or maybe even SIBO was a precursor to IBD, but I actually don’t think so anymore. I think IBD and IBS are completely separate entities. I’ll give you the evidence, I think, and things change with time, but from what I understand currently, food poisoning causes IBS. Anti-vinculin, anti-CdtB antibodies are associated with irritable bowel syndrome, but they’re not associated with IBD. So understanding the pathophysiology of that host infectious IBS tells me, “Well, that develops IBS and SIBO,” but we’re not seeing that in IBD at all, not like that.

The other thing is I would challenge you to find me an IBD patient with IMO. They don’t happen almost ever. We did a study where we looked at breath test in IBD patients and out of a huge list of IBD patients, only three had IMO and all three of them when you called them, they were constipated. They weren’t having diarrhea. They weren’t having IBD-like symptoms.  So I don’t know, but what we do see with IBD is that if they have strictures, they’ll have stasis, and if they have stasis, they’ll have SIBO, and if you treat the SIBO, they will get better, but the reason for the SIBO is not IBS. The reason for the SIBO is a mechanical issue due to the strictures and the narrowings and other things that the IBD produce. So that’s how I see it currently.

Dr. Weitz:                          Many of us will use a low-FODMAP diet for SIBO and I know you have the low-fiber diet from Cedars-Sinai. Do you think that there should be a different diet for patients with hydrogen versus methane versus hydrogen sulfide? A number of practitioners will use a lower sulfur version of the low-FODMAP diet for patients with hydrogen sulfide, for example.

Dr. Pimentel:                     Yeah. I’m getting this question a lot, and I’d like to enthusiastically say that the future is we might have three different diets, but I don’t think we worked out what those diets are yet. I have encouraged some of my hydrogen sulfide patients to go on a low-sulfur diet, but I’m not sure that’s the whole story for them in terms of making them better because I’m giving them antibiotics as well.  So we need more data, more time to unravel that, but what is clear is that from studies done in the past is that people with hydrogen sulfide in their gut that low-sulfur diet does reduce that. That’s been published. So I would imagine that that would, but I don’t have any objective data since the breath test has become available to be able to say, “Aha! This is your diet that you should be on.”

Dr. Weitz:                          Have you seen fasting to be a benefit for patients with SIBO?

Dr. Pimentel:                     I love fasting for my SIBO patients. That’s for sure. I mean, the longer they’re fasted, the more opportunity they have for cleaning waves. The more likely they can naturally clear their bacteria out and so to keep things going. So yeah, I mean, skipping breakfast is something that some of these patients do on their own, but the longer they fast between meals is also part of the low-fermentation diet we developed because it’s not just a diet.  It’s trying to make sure you don’t eat between meals constantly keeping your gut with food and bathing the bacteria with food. It’s not how we used to eat. I mean, thousand years ago, we kill the buffalo, ate the buffalo before it rotted on the field. We didn’t have a refrigerator. We didn’t have potato chips or 7-Eleven. So you eat and then you don’t eat for three days. That’s how life was. Anyway, it’s just-

Dr. Weitz:                          Have you ever recommended patients do an extended fast, maybe a couple of two, three days of water only or something along those lines to calm it down?

Dr. Pimentel:                     I’ve seen patients do that on their own, and that sometimes does work for them, but I don’t generally ask patients to do that because it’s pretty tough.

Dr. Weitz:                          What about the use of the elemental diet? Are you still using that on some patients?

Dr. Pimentel:                     Oh, absolutely. I mean, I’m the one who published that fist trial on elemental diet showing it’s more effective even than antibiotics. So I really like the elemental diet. I think the challenge of the elemental diet is that it is hard for patients to do, but look, we’ve done thousands of patients on the elemental diet, literally. So if we would hit a wall and we want to get rid of the overgrowth, the elemental diet has been quite effective for us.

Dr. Weitz:                          Do you typically do it for two weeks?

Dr. Pimentel:                     So in the study, we have in the past done one, two, and three weeks. So by two weeks, you get your maximum effect and you gain a few percent if you do an extra week, a third week, but I can tell you that there’s two time points in the elemental diet treatment that patients hate me, the first two days and the last three days because in the last three days, they’re like, “I can’t wait till this damn thing is done,” and the first two days, they can’t believe they’re doing this. So the dartboard with my face on it is at the beginning and the end.   You know at the end, what we see is a dramatic response, and then patients, I mean, I have patients who do this three times a year and they just love it. They have the fortitude to do it and it makes them feel better than antibiotics. So it’s not all negative. I don’t mind being the face of the dartboard if it makes the patient feel better.

Dr. Weitz:                          Do you ever see patients who started out maybe as hydrogen SIBO and end up as hydrogen sulfide SIBO or switch from one form to the other?

Dr. Pimentel:                     So we’re still early in the hydrogen sulfide part of things, but I have almost never seen somebody switch from hydrogen to methane, but I have seen if we get rid of methane all of a sudden the hydrogen goes way up because it was always there. It had to be there to make the methane. So I have seen the flip side, but never going from hydrogen as their baseline after treatment to methane, almost never. Maybe one in 10 years that I saw that happen.

Dr. Weitz:                          We got a couple of questions about the elemental diet. Are you using the integrative product or what product are you using for the elemental diet?

Dr. Pimentel:                     Yes, I’ve used sometimes the integrative diet. Sometimes I use Vivonex. So those are mainly the two products. Peptamen because it’s almost elemental, it may be more palatable for some patients, but those are the two products I mainly stick with.

Dr. Weitz:                          With the elemental, they have a version with dextrose and one without dextrose.

Dr. Pimentel:                     I don’t think it matters to me the dextrose because I think it gets absorbed so quickly it doesn’t really affect the situation. I do have patients who ask me about whether they could have coffee while they’re on it. I always answer, “Well, the study was done with no coffee. If you do coffee and you don’t get better after, don’t blame me,” because I don’t know. I mean, it’s neutral. It’s calorie neutral, but they always ask me all sorts of questions.

Dr. Weitz:                          When I put patients on the elemental diet, I usually give them herbal antifungals because of the possibility that they’re eating a high-sugar diet that can fuel the growth of candida or other fungal organisms.

Dr. Pimentel:                     Yeah. Well, I for sure see candida especially thrush in their mouth on the Vivonex and elemental diets. So, yeah, that’s not an unwise thing.

Dr. Weitz:                          Okay. So I’ve seen where you had a chart of what the microbiome looks like in patients with SIBO and there’s real limitation of a lot of the healthy organisms and you end up with overgrowth of proteobacteria and Firmicutes in particular seem to be really suppressed in patients with SIBO.

Dr. Pimentel:                     Yeah. That’s correct. That’s exactly what we see in the small bowel.

Dr. Weitz:                          So does it make sense to use certain types of probiotics to take up that space that’s been vacated so that we make it more difficult for the proteobacter to continue to occupy the small intestine?

Dr. Pimentel:                     I would love for that to be developed, but I don’t have any evidence to suggest that that would work at this point. The evidence suggests it could work, but I have no evidence to suggest that it does work. One of the things that we’re seeing in another paper is that lactobacillus is a disruptor of the small bowel. It’s doing things like E. coli is doing. So you look at lactobacillus, “Oh, it’s good for your colon. It’s good for your colon.” It’s not good for your small bowel I can tell you that now and you’ll see some data coming out shortly on that. We’ve already talked about that previously. Lots of new things coming in and I’ll be adding that to my slide shortly.

Dr. Weitz:                          Yeah. There’s some new probiotics on the market. There’s now an Akkermansia muciniphila, which is one of the important Firmicutes, which had to be produced in a non-oxygen environment, very difficult, and they finally brought it to market. I wonder if that would be something that would make sense to try to regrow the Firmicutes.

Dr. Pimentel:                     Well, if I know Akkermansia well, it also makes a lot more mucous. So are you making more environment for proteobacteria to hide or I don’t know. I’m not criticizing. I think we have to do more work. I think it’s interesting. I think having it gives us the opportunity to look at those kinds of questions, but, yeah, I’m still not clear yet.

Dr. Weitz:                            Yeah, because I mean, even if we kill the E. coli or the other organisms, we still want to regrow the healthy bacteria in the small intestine. So I wonder if maybe prebiotics would be beneficial.

Dr. Pimentel:                     Yeah. I mean, all of that is on the table. So, again, Ben, I’m not pushing back. I just won’t know what the cocktail will be, but what I think I show and I think the slide you’re referring to or the depictions you’re referring to is the network analysis that we did.  The network is not one organism. It’s not three organisms or five organisms. It’s 100. So what I would love to do is to see the 100 come back and not in a fecal transplant because feces are not the composition of small bowel, but we should do a small bowel to small bowel transplantation, and then we might be talking this stuff. I wish we have that because I think that might be the trick, but single organisms, I don’t know. I have to see.

Dr. Weitz:                          Yeah. Is that something you’re working on?

Dr. Pimentel:                     Not small bowel transplant, not yet. No.

Dr. Weitz:                          Okay. So what’s the best way to reset the motility of the gut?

Dr. Pimentel:                     I really like using prucalopride Motegrity to push motility when it’s down. You can also use low-dose erythromycin. That’s what we old school did. Low-dose naltrexone does some of that, too. I know some people use that, but I like Motegrity now. I’ve had a lot of good success with it in the last couple of years.

Dr. Weitz:                          What do we know about patients who have histamine intolerance and SIBO?

Dr. Pimentel:                     Well, I mean, there are histamine-producing bacteria in the gut. So we have to find those characters and characterize them. Histamine is a really difficult thing. The histamine chemical has a very short half life, hard to measure. So we’re trying to track those characters, but we’re not having a good success with that yet. Stay tuned. We are trying to get at them, though.

Dr. Weitz:                            Okay. I think that’s pretty much all the questions I have. Let me just look through the questions that people have asked here. FODMAP diet, let’s see. Somebody asked, “If you were to use rifaximin plus allicin, would you only do it for two weeks?” which is the way you typically use rifaximin versus when we use herbs, we typically use them for four to six or eight weeks.

Dr. Pimentel:                     So I do use allicin in the form of Allimed is what I generally use. Usually, by itself, and I get some good success with methane. The problem with the allicin is over time the methane returns. Sometimes I keep them on it indefinitely to try and keep it down, but then methane still breaks through. It only goes down for a while.

Dr. Weitz:                          Have you used Atrantil?

Dr. Pimentel:                     I have a few patients on Atrantil and some success there. I don’t use it routinely, but, yeah, I have a few patients who benefit from it.

Dr. Weitz:                          Okay. I think that’s all the questions. Thank you so much for your time, Dr. Pimentel. Any final thoughts you want to leave us with?

Dr. Pimentel:                     No, Ben. You always challenge my brain with the most difficult questions, but I love it because there’s still a lot to learn, obviously, and I can only tell you what I know and I hope that in three months I’ll be able to tell you a lot more of what we’re finding this month and next month and just keep you guys informed, but thank you for all you guys do. I think it’s a challenge to treat these patients, and I know we’re all working together to try and find better treatments.

Dr. Weitz:                          Absolutely. Thank you everybody for joining and we’ll see you next month. Thank you so much, Dr. Pimentel.

Dr. Pimentel:                     All right, Ben. Thanks again. Take care.

Dr. Weitz:                            Thank you for making it all the way through this episode of the Rational Wellness Podcast. If you enjoyed this podcast, please go to Apple Podcasts and give us a five-star ratings and review, that way more people will be able to find this Rational Wellness Podcast when they’re searching for health podcasts. I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica Weitz Sports Chiropractic and Nutrition Clinic. So if you’re interested, please call my office 310-395-3111 and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you and see you next week.

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Dr. Isaac Eliaz speaks about The Survival Paradox with 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

3:45  The Survival Paradox is that what helps us survive is also what shortens our life.  Inflammation is often referred to as the cause of chronic disease, but what really causes inflammation?  Inflammation results from our survival response, which is our sympathetic nervous system response, our fight or flight reaction.

7:48  Our biochemical survival response centers around a group of proteins called alarmins, of which the driver is Galectin-3.  Galectin-3 is expressed within minutes from tissues under stress and it has the ability to bind to different carbohydrates and it can bind to sugars, to glycolipids, to oxidized lipids, to heavy metals and other toxins.  Galectin-3 is involved with every chronic disease.  Short term inflammation is good because it promotes healing, while long term chronic inflammation can be problematic.  Galectin-3 is a more upstream molecule, while many of the other inflammatory mediators like Interleukin-6 and TNF alpha are downstream molecules.  This is why just neutralizing Interleukin-6 may not work. By addressing galectin-3, we cut down the whole inflammatory process.

10:12  The survival paradox is our whole experience of life. It’s how we treat ourselves, our microbiome, our family, and our community. It’s how we treat people who don’t agree with us. It doesn’t work when we fight.  The architect of the Survival Paradox is Galectin-3 and it can be blocked with modified citrus pectin.

Dr. Isaac Eliaz is a medical doctor and acupuncturist and he has been a pioneer in the field of integrative medicine since the early 1980’s. He is a respected researcher, formulator, author and clinician. He has published dozens of scientific studies, esp. related to Galectin-3 and modified citrus pectin, the nutritional compound that he developed that can inhibit galectin-3.  He has a busy private practice in Santa Rosa, California, the Amitabha Medical Clinic with a focus on cancer, Lyme disease, and other chronic illnesses and he has just published his new book, the The Survival Paradox: Reversing the Hidden Cause of Aging and Chronic Disease. 

Dr. Ben Weitz is available for 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.

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, I’m very excited today to speak to Dr. Isaac Eliaz about his new book, The Survival Paradox: Reversing the Hidden Cause of Aging and Chronic Disease. When we are facing threats to our survival such as trauma or disease, this triggers our stress response, which is also our survival response. This does allow us to run from a lion, but it doesn’t help us to marshal our immune response to fight off cancer or heal from many of the other inflammatory chronic diseases that are the major killers for today. This stress response triggers inflammation, and the activity of galectin-3, which is an inflammatory protein that can harm us if it is not controlled.  Dr. Eliaz refers to galectin-3 as our survival protein, and research shows that it is involved in quite a number of chronic diseases, including Alzheimer’s disease, arthritis, heart disease, diabetes, chronic kidney disease, liver fibrosis and metastatic cancer. Fortunately, there is a way to get rid of and control galectin-3, and that’s this incredible nutritional compound that Dr. Eliaz developed, known as modified citrus pectin, and known as Pectasol-C. Dr. Isaac Eliaz is an MD, an acupuncturist and he’s been a pioneer in the field of integrative medicine since the early ’80s. He trained in Tibetan Buddhism for decades. He’s a respected researcher, formulator, author and clinician. He’s published many scientific papers, especially related to galectin-3 and modified citrus pectin. He has a busy private practice in Santa Rosa, California, the Amitabha Medical Clinic, with a focus on cancer, Lyme disease and other chronic diseases.  He’s advanced the use of plasma apheresis, as well as other groundbreaking treatments for cancer and other inflammatory conditions. Most importantly, Dr. Eliaz is a wonderful human being who cares deeply about his family, his patients, and the planet, and he’s been contributing to promoting the interests of all of them. Isaac, thank you so much for joining me again today.

Dr. Eliaz:              Hi, Ben. It’s so good to talk to you again. I love our talks, and thank you for the warm introduction. I really appreciate it.

Dr. Weitz:            Absolutely. It’s always a pleasure to speak to you. Congratulations on getting your book, The Survival Paradox, published.

Dr. Eliaz:              Thank you, thank you. I’m very excited about it. It actually launched today, so I’m so glad to talk to you on launch day.

Dr. Weitz:            Now, I think this book is a long time in the coming, right?

Dr. Eliaz:              Yes. This book specifically, I worked on it for three years, with the help of a lot of people, but it expresses decades of studies, of contemplation, of clinical work as a clinician, as a doctor, as a Chinese medical doctor and as a healer. Together with decades of training in meditation, and it kind of all came together in the realization of The Survival Paradox. It’s something, it’s that’s hard to wrap our head around it. It’s actually what helps us survive, is actually what shortens our life. But this is really what paradox is, right?

Dr. Weitz:            Right. Tell us a little more about what the survival paradox is.

Dr. Eliaz:              There are different angles to look at it, but I actually want to take an angle that you like, because you like biochemistry. We recognize now that inflammation is a driving force for every chronic disease, right?

Dr. Weitz:            Yes.

Dr. Eliaz:              So in integrative medicine, we know it for quite some time. I mean, I have been referring to it in an intense way for about 30 years, and people in the last 20 years, and now I think the uncontrolled inflammation cytokine storm has come to the forefront. But is inflammation really the cause? It’s really not the cause. Inflammation is a result, so we are stuck with treating the result without looking at what caused the inflammation. Well, what causes inflammation is our survival drive.  And so that’s the first major contribution of the book, is I take the audience, the biohackers, longevity people, or the mind-body people, the people with chronic diseases, the doctors, the healers and I now say, “Okay. We know about inflammation, but this is just a result. That’s really an expression of what? Of our survival drive.” How can it happen? We are innately built to survive, it’s built within us. It’s our ego clinging, it’s our identification and it has been like this forever. Every living being wants to survive, and if it’s true, it has to be automated, and we can’t control it, and that’s the case.  We have an automatic survival response too, and from your work with your patients you know it so well through your autonomic nervous system. The sympathetic response is the survival response, it happens in milliseconds, and we get a sympathetic flow. Then when we get out of survival mode, the body relaxes by being balanced with the parasympathetic, so survival response sympathetically is either fight response, with changes in breathing, in heart rate, in circulation to the digestive system, bladder, sweat, et cetera. We don’t need to go into the details. And then we either fight or we run away. When we run away, we move into survival metabolism, we move into glycolysis. That’s why short-term sprinting doesn’t use aerobic metabolism, it uses glycolysis.

Or we go into fear, we hide, we shield ourself. Ideally, we respond and then we can relax. In ancient time, we were in danger, and then we got out of danger, we relaxed in our hut, around the fire and the parasympathetic system now is just… This is not the days. We are now at the sympathetic flow all the time, because we get text messages and radiation and cosmic radiation and computers, and people want us to respond in seconds. We are in total sympathetic flow. This by itself degrades the immune system, degrades our whole being. It’s profound, but then… But we still have a chance to balance relatively quickly. If we go on the weekend and relax, we feel the difference.  We can talk a lot about it, why it’s so hard to come back from a vacation.  Why we get exhausted when we come from vacation, why everybody experience it.  Because we change our receptor ratios on the surface between parasympathetic and sympathetic.  We’re not ready to the sympathetic heat, but that’s a side topic.  If you want, I’ll revisit it. But then we got our biochemical survival response, and the driver of the biochemical survival response is a group of proteins called alarmins.  The driver is galectin-3.  And why?  Because galectin-3 is like the bus, like the train, like the skeleton. It gets expressed within the minutes from the tissue that is under stress, and it has the ability to bind to different carbohydrates, or it can bind to oligosaccharides, to glycoprotein, protein with sugars, to glycolipids, oxidized lipids that carry also heavy metals and toxins and to different growth factors. It carries them to wherever the body wants, so we’ve got this basic structure that is so versatile, it can affect every possible disease. Indeed, galectin-3 is practically involved with every chronic disease.

Dr. Weitz:            But you’re also seeing that there’s some benefits to galectin-3 in the short term.

Dr. Eliaz:              Absolutely so.

Dr. Weitz:            Just like there is with inflammation. Short-term inflammation is good because it promotes healing. It’s the long-term, chronic inflammation that can be problematic.

Dr. Eliaz:              Absolutely, so the long-term sometime is 10 minutes, it’s already long-term, the response. Galectin-3 indeed, it starts the injury repair, but it doesn’t turn off. Now, galectin-3 is really the upstream molecule and all the cytokines follow down, so a lot of treatment that try to neutralize interleukin-6 remove cytokines, they’re not working, it’s too late. If we look at changes in the level, if somebody’s at the top of the arrow, you don’t need to… Right here, Ben, there is a very small change. Look, from here to here, it’s a tiny space. But look what happens when we go down, now we got this amount of space, so galectin-3 will go up by 50%. Sometimes will double, few reactive protein interleukin-6, TNF alpha will go up a thousand times, because these are downstream… These like a whole waterfall, whole cascade.  By addressing galectin-3, we cut down the whole inflammatory process. That’s the physical biochemical aspect of a survival product. It’s only one aspect, survival product is our whole experience of life. It’s how we live our life.  It’s how we treat ourselves.  It’s how we treat our microbiome.  It’s how we treat our family, our community. It’s how we treat people who don’t agree with us.  It’s all the Survival Paradox.  It doesn’t work when we fight, it never worked and never will work, it’s a short term solution. Understanding this, we start to get a deeper glimpse of the Survival Paradox.  In the book, really I take the reader through the whole journey.  What is the Survival Paradox?  Who is the architect of the Survival Paradox?  Galectin-3. The effect of a survival response.  How it’s created, and then how it affects inflammation and fibrosis. How to block it with modified citrus pectin.  Then I talk about the pivotal chapter in part one, is the heart of survival. How is the survival of the heart is our key to transformation, because the heart survival energy, the heart survival role is to transform the survival role. It’s built within us, that’s the beauty of it. Otherwise, what’s the point of writing a book if there are no solutions? Then I go… So people, it’s like a wow. I’ve had people who are practitioners for decades, or people who are medical writers who have had chronic disease for decades and they tell me, “Isaac, I didn’t really realize it until the book was done.”  They tell me, “No, Isaac, I’ve been in this field for 30 years. I’ve been treating my problem for 30 years. You turned my whole thinking upside down, I was totally off. I didn’t get where the problem is.” Then I take this, and I go through every serious disease. Of course, I do a lot of cancer work, so the biggest chapter is cancer. Then I go about heart disease and kidney because they are related in Chinese medicine, water and fire. As a side comment for anybody studying or practicing Chinese medicine, this book has jewels of Chinese medicine. From decades of esoteric studies of Chinese medicine, and I kind of sprinkle them through the book. Then I go, liver, and lungs, so I cover the basic organ system. I go through the metabolic system, which I know you’re so interested in. I go through the neuro inflammatory system.  I go through the immune system and I go through the microbiome. Then I start talking about solution.  I present detoxification in a much bigger picture, much broader understanding than just eat this or do that.  Then I go to maybe my favorite chapter, or the three favorite chapters.  Is the healing our scars of survival, how we heal our scars, our physical, mental, emotional, psychological, psycho spiritual. Our scars and discover the full ancestors. Genetic and more important, epigenetic. I really go through what a cell goes through, because a cell is a living creature. It has boundaries, it decides what comes in and what goes out, and it can make some decisions. Sometime good decisions, like it wants to play with the environment and be in harmony, and sometime it goes into survival paradox mode and wants to survive.  It doesn’t care about the environment, it creates a micro environment. It doesn’t communicate with the system, it becomes more aggressive. How do we call it? We call it cancer. 

I talk about how to heal scars and I give my own story. Being a holocaust family from a Holocaust survivor, how my grandmother responded, how my grandfather responded who named after. My mother, then how I by healing my Holocaust trauma which wasn’t mine, was from my grandfather which I didn’t know but I’m named after, took away all my symptoms after 60 years. And how my mother healed without knowing that I healed my own, it’s a beautiful story. Then I go to the real depths of transforming the survivor paradox, at least from an understanding. It takes years of practice. Is a survival response really the cause? Not really.  What causes the survival response? What causes survival response is the survival response. We cannot accept that everything changes. That everything that is born, everything that expresses itself is going to fall away, a very basic Buddhist principle. We don’t accept impermanence, we solidify our experiences. That’s the essence of survival, we don’t want things to change.  How do we change it?  Through the book, the emphasis from modified citrus pectin, from lifestyle, from specific advice in the light of survival, so whatever for the practitioners, you’ll do the same stuff you do. But you love a different flavor, you love a different understanding, different eyes. Then I go through the major transformative organ, and we are built to transform our Survival Paradox, is the heart.  Through the book, I give dozens of stories of my heroes and of my patients, how they healed. Sometimes they healed and the disease went away, and sometimes they healed and they died, but they still healed. These are very inspiring stories, and it was hard to choose who to put in there wasn’t space for everybody. But I got the vast majority of my heroes in, and so it’s inspiring, it’s really. The book is alive and I really think it’s almost like a manual that you can read. It’s very con… On one level, it’s an easy read. It’s very, because my precious daughter, Lily, really upgraded the writing and editing. She’s a brilliant writer and it comes from my heart, you can feel it. But it really has, it really has a lot of valuable information.  Then at the end, I provide close to 80 pages of valuable appendices, so practical, detox protocol, diet protocols, what supplements for which conditions, what dosages. I give them practicality, but I don’t exhaust the reader with the details. I want to teach the reader how to change things, instead of just giving them five steps for this, eight steps for this. In this sense, yeah I think the book can really help many people. That’s the feedback I’m getting from… Sometime, it’s almost shocking to me.

Dr. Weitz:            Interesting. I’ve really been enjoying this discussion, but I’d like to take a minute to tell you about a new product that I’m very excited about. I’d like to tell you about a new wearable called the Apollo. This is a device that can be worn on the wrist or the ankle, and it uses vibrations to stimulate your parasympathetic nervous system. This device has amazing benefits in terms of getting you out of that stressed out sympathetic nervous system and stimulating the parasympathetic nervous system. It has a number of different functions, especially helping you to relax, to focus, to concentrate, get into a deeper meditative state, even to help you sleep, and there’s even a mode to help you wake up. This all occurs through the scientific use of subtle vibrations.

                                For those of you who might be interested in getting the Apollo for yourself to help you reset your nervous system, go to apolloneuro.com and use the affiliate code, Weitz10. That’s my last name, WEITZ10. Now, back to the discussion.

Dr. Weitz:            Every time I talk to you about galectin-3 and modified citrus pectin, this whole story is so amazing and I always come away from the conversation going, “This is amazing. This is so important and I’m just shocked that nobody else is talking about it.”

Dr. Eliaz:              Well, it’s a little bit my life journey. I’m kind of always ahead of the curve. It’s a very lonely journey. I’m used to it, I like it. I’m used to it, but really the only person often you can talk to is yourself, and then get back to-

Dr. Weitz:            I talk to myself all the time.

Dr. Eliaz:              I know, now look I talk to doctors, I can understand their language. I understand they can’t really understand how I think most of them. If I find somebody who does, my God, I’m rejoicing. My family can. And they both say my precious wife [Gillen 00:19:26], my daughters, one with a spiritual teacher Lihui, and one who is finishing medical school in UCSF.

Dr. Weitz:            That’s great.

Dr. Eliaz:              They have this kind of understanding. But you know… We talked about chronic disease, but what we have realized in the last few years, is that galectin-3 is a driver of acute disease, myocardial infarction, but most important sepsis. So actually-

Dr. Weitz:            Wait a minute. The galectin-3 is a driver of myocardial infarctions?

Dr. Eliaz:              It will make myocardial infarction worse.

Dr. Weitz:            Okay.

Dr. Eliaz:              And yes, but for example, If somebody goes and get… When we look at acute damage to the body, the most important organ that affects our whole health despite the heart when it stops working, it’s our longevity organ, in Chinese medicine is the kidneys. Very often we in sepsis, in crises, in circulatory problems, we get what is called acute kidney injury, AKI. Very common, completely overlooked and as a dear friend of mine, really a giant in nephrology, Dr. Prof. Glen Chertow. He’s the head of Stanford nephrology. Says, “You know, Isaac, people die because of AKI, not with AKI.” He’s been trying to say it for decades, and this has been my observation, not being a nephrologist, and galectin-3 drives it. I’ve published two really important papers with great authors.  With the person who is the most well known, critical care doctor in the world ranked number one, with John Kellum and other very well known doctors. We showed that when a patient comes to the intensive care unit with sepsis, with no pre-existing conditions, they got a blood infection, the level of galectin-3 at the time of admission will determine who will get acute kidney injury and who will die during the ICU, it’s insane.  No other markers is better.  A patient did get a coronary artery bypass, people don’t know.  One of the reason and the fears of doing coronary artery bypass, is acute kidney injury, 10% to 30%, 5% to 10% get serious kidney damage and 2% to 5% die.  None of them should die, because most of the surgeries are elective surgeries.  You find there the problem and you do the surgery.

The level of galectin-3 before admission to the surgery, will determine who will get AKI in this study we published. The level of galectin-3 when you leave the surgery and go to the intensive care unit, is the best marker in who will get AKI [inaudible 00:22:14]. And in the most acceptable animal model, both for sepsis and for circulatory injury, acute kidney injury, when we gave Pectasol for a week before the procedures, the animals that got it had a dramatic decrease in AKI and mortality. Another thing that I’m developing galectin-3 apheresis, when we took animals with the septic model and we filter the blood with a specific antibody that removes galectin-3 from [inaudible 00:22:48], eight out of nine of animals where the column was empty, shame column what we call fake column.

Eight out of nine died, compared to only one out of ten, is the one who got one single apheresis. And try, because when you remove galectin-3 very early on, an hour after the injury, interleukin-6 goes down and kidney damage goes down and survival goes up. This shows us, how is this survival response uncontrolled, and it’s all happened in an hour. Long term is not two weeks. You know, the burden is a massage and relax. Babies know how to do it. When we get a cut when we are babies, it heals right away. But our bodies we have more injuries and we have more traumas, and our metabolisms changes. We lose our resilience, our flexibility and this loss of flexibility affect our injury repair. But not only physical, emotional, psychological. We see it in medicine.  I will study a certain area in medicine whatever belief system, and then three years later I will see something that is different than this, I let go of the other thing, that’s okay. Doctors usually cannot handle it, they feel threatened. Why do they feel threatened? Survival response. This is a survival part of… Ben, is deep, it’s really who we are. It can really transform our life, it can connect us with our heart because their heart is the organ that is built to transform the Survival Paradox.

Dr. Weitz:            It’s interesting. I was just talking to another doctor about a patient who has acute rhabdomyolysis and his creatine kinase went high and doctors are saying that if it doesn’t come down right away, he could have acute kidney injury. Would galectin-3 also be a factor in his condition?

Dr. Eliaz:              Usually yes, because of the acute. But the problem here, that the kidneys are bombarded with rhabdomyolysis, that just blocks the nephrons. It’s like a filter that is full of stuff and can’t filter anymore. But yes, you have to reduce the inflammatory response and definitely, but it’s a little bit more of like an unusual reason. The most common reason for AKI is sepsis and perfusion injury, blood is not getting to the place.

Dr. Weitz:            Yeah, this was just from somebody over exercising.

Dr. Eliaz:              Exactly, very important. In the book, I talk about over exercising. That is not a good thing, and it’s very interesting. Then I kind of made my statement melaware. But that’s exactly, when we exercise too much, we put strain on our system and the changes the metabolism. Wow, that’s quite something from over exercising. This person must have really over exercised, my gosh.

Dr. Weitz:            Is galectin-3… Is it contained in our diet at all?

Dr. Eliaz:              No, galectin-3 is a protein produced by the body.

Dr. Weitz:            Okay.

Dr. Eliaz:              It’s produced by macrophage, it produced at the tissue level, but we have to remember, we are not the only ones who want to survive. Cancer wants to survive, so it will use galectin-3 to shut down the immune system. For example, cancer patients getting immunotherapy, if their galectin-3 level is high, they will not respond to immunotherapy, it’s well known, it is very expensive treatment. But infections also want to survive, our microbiome wants to survive. When we tweak our microbiome well with harmony, then microbiome serves us. It even activates chemotherapy in cancer, it activates immunotherapy. When we attack our microbiome with inappropriate diet, with stress, with antibiotic, the microbiome will respond with a survival response. How will it respond?  By utilizing galectin-3 to dock into the lining of the gut and create a biofilm. Galectin-3 is the skeleton of the biofilm. Here is an example of a relationship between us and the microbiome. Now, obviously we are in this insane pandemic where COVID wants to survive. The spike in protein of the COVID is practically identical to galectin-3, identical okay. Galectin-3 blockers will play a huge role in preventing severe COVID, because that’s the same survival drive. There a lot of galectin-3 receptors in the lungs, highest amounts in the body. For example, a large study from Mexico City from a very good day. The last author is a very good researcher and physician who I published with, I kind of turn it on into galectin-3 when she was in Harvard, and she helped with my apheresis study, brilliant woman. They did a study in the emergency room checking COVID patient coming to the emergency room. The level of galectin-3 in the ER, regardless of the amount of involvement of the lung, at the time of admission, determine the severity of the disease and who will die.

Dr. Weitz:            Really? What was the cutoff for severe COVID?

Dr. Eliaz:              For them, it was 30. But you know, I wouldn’t jump on it. It’s a big issue, because there’s so many different kits and methods, and that’s a very important message for the clinician. Now we’re moving more into galectin-3 in a way with the Survival Paradox. Don’t tailor your treatment of using modified citrus pectin, to the level of galectin-3. Galectin-3 levels, are very complicated, in the diagram if I can find it quickly while we talk. If you can look at here, you can see that galectin-3 can be in pentamers-

Dr. Weitz:            Right.

Dr. Eliaz:              Five, and monomers.

Dr. Weitz:            Okay.

Dr. Eliaz:              The antibodies that detects galectin-3 and the diagnostic counts this as one. Because it binds here, it comes this is one. People have more monomers will have higher level of galectin-3, and it’s a genetic MMP-9 effect. There’s a total balance between the two, so you really give modified citrus pectin, based on the health of the person. That’s why, who needs to address galectin-3? Anyone that is breathing. I’m not exaggerating okay, Ben? Anybody above the age of 30 has to start taking modified citrus pectin daily. It’s the most important supplement, not because I developed it. Again, all the research was done on Pectasol, we have now 72 papers. It’s because galectin-3 drives every chronic disease, some of them you don’t see the effect.

You can use your supplements, and you can use your herbs and you can use your drugs, you can do chiropractic adjustments, you can do acupuncture, MCP will help the results, because it allows the medicine, whatever you’re doing to get into the problematic tissue. It reduces inflammation, it stops the fibrotic process, it regulates immune response and it removes heavy metals, and toxins and mold toxins. It’s really this gift from nature, and when we started the journey, I collaborate with Dr. Avraham Raz, which is really the person who discovered the galectin-3 and the use of modified citrus pectin in the early ’90s. Then I discovered a lot of the uses of modified citrus pectin, and we published one very important paper recently together and we work together. We always say to each other, it’s amazing.

We never thought 30 years ago, 25,26,27 years ago for me, that galectin-3 would be so big. It was really all about cancer metastasis, again, survivor of the cancer. Malignancy helped it metastasize and attack. Then it affected the primary tumor. But I started observing in the late ’90s, an anti-inflammatory effect. Joint pain, memory, blood pressure getting better and I made this very important discovery that in inflammation and fibrosis, people thought I’m crazy. 10 years later, it became known and now it’s the focus of so many universities. A lot of [inaudible 00:31:46] science after my work, but it’s fine. It’s nice when other people follow what you discover. But it’s a fundamental supplement in every program, and I’ve been very bad in putting it out. The ratio between research and how known it is, is not good. There’s so much research and people are not aware of Pectasol. It’s a must.

Dr. Weitz:            Right.

Dr. Eliaz:              For people who are sick, they really need to take 15 grams a day. We see it with joint pain, with digestion, with Lyme disease, mycotoxins, protection especially chronic kidney disease. People who have deteriorating kidney disease, unless they’re really close to a total failure where they have a problem with what they’re taking, they should take a lower dose if their EGFR is under 15. They got to use modified citrus pectin. It will most probably slow the process, stop it and some people it completely reverses. I’ve people were like, “Were deteriorating quickly. We’re already stage three chronic kidney disease.” They just added Pectasol and they completely reversed, which is unheard of.

Dr. Weitz:            Purpose it would be like 15 grams a day?

Dr. Eliaz:              Yeah, until you get to the late stage, full dose. Because guess what? Also it protects your heart. It protects your brain. It protects your circulation. The kidneys are not an isolated event, so our focus with apheresis for example, isn’t sepsis and acute kidney injury. We really believe that if we take out galectin-3, we know it from the studies, we show it now in the animal studies. If we take galectin-3 from a septic patient right away, they will not die. You know how many? Hundreds and hundreds of thousands of people a year die from [inaudible 00:33:39]. Millions, 11 million over the year die from sepsis.

Dr. Weitz:            Right. Your apheresis is when you take the blood out, filter it out, like in this case, filter out the galectin-3 and then put it back in?

Dr. Eliaz:              Yeah. Again, this is in development. We’re three four years away if we raise enough money. But you know, we own a favorable path. We got committed people working with us, and so it’s very exciting. Meanwhile, in the clinic I use a different device, an LDL apheresis. It just pulls out oxidized lipids and inflammatory compounds, kind of like the downstream effects. But we are still seeing very significant benefits. But in my opinion and again, I’m a cancer guy. But now I’ve accumulated enough patients, that practically almost everyone with chronic kidney disease is benefiting. It’s insane, people don’t notice. You ask Reagan and Fuller, can you improve Chronic Kidney? I can… It’s possible to improve chronic kidney disease. I’ll tell you, listen. Did you drink a bottle of vodka last night? It’s impossible. What are you talking about?

Dr. Weitz:                            I’d like to interrupt this fascinating discussion we’re having for another few minutes to tell you about another really exciting product that has changed my life and the life of my family, especially as it pertains to getting good quality sleep. It’s something called the chiliPAD, C-H-I-L-I-P-A-D. It can be found at the website chilisleep.com, which is C-H-I-L-I-S-L-E-E-P dot com.

So, this product involves a water-cooled mattress pad that goes underneath your sheets and helps you maintain a constant temperature at night. If you’ve ever gotten woken up because temperature has changed, typically gets warmer, this product will maintain your body at a very even temperature, and it tends to promote uninterrupted quality deep and REM sleep, which is super important for healing and for overall health.

If you go to chilisleep.com and you use the affiliate code, Weitz20, that’s my last name, W-E-I-T-Z, 20. You’ll get 20% off a chiliPAD. So, check it out and let’s get back to this discussion.

Dr. Weitz:           Is galectin-3 affected by non-steroidal, anti-inflammatories, corticosteroids, any of the other anti-inflammatories, curcumin. Do any of these things affect galectin-3?

Dr. Eliaz:             The one below galectin-3, but when inflammation gets better, over time galectin-3 will go down. We have to understand, I published a very interesting case report on a cancer patient who had an autoimmune disease. As I was helping your autoimmune disease and the cancer was still growing in preparation for chemo, the galectin-3 actually came down while the OC125 went up. But then she had this insane response to chemotherapy because she wasn’t inflamed anymore. Yes, so it’s a result again. Inflammation, it’s a result of reduction in inflammation. Inflammation is very tricky, because you can have over inflammation very common, but you can have under inflammation. One of the group of people with inflammatory response is in appropriate and they go more into fibrotic response is Lyme patients.

You can see in Lyme patients that C-reactive protein will be very low, almost universally. TGF beta 1 if fibrotic marker stimulated by galectin-3 will be very high. And galectin-3 will be very low, because they lost their repair capacity. You give them modified citrus pectin, or you do apheresis, you regulate it. CRP goes up to normal, so from undetectable it will come to 0.2. TGF beta will come from 20,000 to 5,000, 6,000 and galectin-3 will go up from three or four, which is under to 6,7. It’s very important for practitioners, and holistic doctors know this. When you look at the blood test, forget the norms. Because standard or standard, standard is very loud. The standard here is very different than standard here. Sometimes blood tests are illusionary, just like the cause of diseases.

You can see a cancer patient with no inflammation. You do apheresis, nothing comes out. How exciting? No, I know it. I’ve experienced it. I look at every filter, I can see the patient, it’s a insight. The disease is so anchored, that the body is not releasing it. Or it’s very, it’s very deep and the body cannot reach it. You treat the patient, suddenly the markers change, they come into the middle range. Now they’re expressing, suddenly they start pulling all the toxins until they begin the apheresis. MCP, Pectasol and addressing the Survivor Paradox, addresses it. We have to peel off this shell, this protection and then the body can make its changes, and that’s the depths of the Survivor Paradox. Again, modified citrus pectin is one very important essential part, it’s only part of the picture. The real transformation of the Survival Paradox is connecting with our heart, which I would like to explain unless you have another question.

Dr. Weitz:            Sure, go ahead and explain that.

Dr. Eliaz:              If we look at our body and really unlike it… every time I think about it. We have about… I like to round it to 50 trillion cells. Some people say 37.5, I have no idea why they got to this number. 50 trillion, okay so not million. Million times a thousand is billion. And a billion times a thousand is trillion. 50 trillion cells. Each cell, Ben, can have between hundreds of thousands to 1 million reactions a second. A second, okay?

Dr. Weitz:            Right.

Dr. Eliaz:              We got 50 trillion cells going through 1 million reactions, okay. So it’s 10 to the 13, times 10 to the 6. So it’s 10 to the 19, almost Avogadro number. Almost like like you know… It’s insane, almost infinite. Reactions, every second okay? All of this in our body, plus 100 trillion organism in our microbiome, and we all function and we are alive. If you don’t call this a miracle, I don’t know what is a miracle. It’s a miracle of life. We have to really appreciate it. How can it happen? Because of mutual support. Because each cell understand, it’s a part of a bigger system. When this falls away, when we get trapped in the Survival Paradox, that’s when cancer starts, autoimmune starts, stress and suffering starts, fight starts and it affects everybody.

The cell knows that it’s a part of the system, but it still wants to survive by itself. How does the cell does it? It chooses what to take in, and what to take out. It has a semi permeable membrane round it, it as receptors. Now, of course the receptors can be affected by the environment and the cell doesn’t have so much choices. By default, the insulin receptors are blocked. There is no normal glucose metabolism. AMPK get blocked until one goes out. You’re going to glycolysis. You either get metabolic disease or you get aerobic glycolysis Warburg effect in cancer, so the cell is part of the environment. The cell has to take care of the environment as it can’t care for itself. But the cell excretes what it doesn’t want into the environment.

Then suddenly, we’re in a tissue and liver and I would love to give the kidney example. If the kidney feel that it doesn’t get enough blood, doesn’t get enough oxygen, it just goes into survival crisis. What happened when we can breathe? We go into survival crisis. What does the kidney does? It says, get me more blood. This happens whenever we have sclerosis in the kidneys, or you have renal artery stenosis. What does the kidney do? It excrete vasopressors to increase the blood pressure. The heart now pumps blood at pressure. What does it do? It increases the damage to the kidneys. The kidneys get less blood, eventually the kidney will go into failure, the most common cause of kidney failure and that will happen doing [Keber 00:43:01], during surgeries when you shut down the circulation.

And eventually the body will die. Every organ is for itself, except one organ in the body, our heart. Our heart’s survival, it takes dirty blood from all over the body. Whatever other cells don’t want, the heart accepts with an open heart. it doesn’t say I’m going to take blood only from the liver, but not from the lung, or not from the brain, or not from your right foot, it takes everything. Remember, from a timing point of view, anything getting to the heart belongs to stuff from the past, that was released from the cells and let go. All this stuff we’re letting go from the past so it can be a molecule that the cell got an hour earlier and it doesn’t want. But it can also be a carbon molecule, that the cell got 30 years ago while the body was going through trauma and now the cell released it like during detox, so the heart takes all of it.

Instead of fighting, saying no, I’m not going to give it like a cell can shut down, arterioles can contract and expand. The heart simply connects to the universe through the lungs, through the breathing. The lungs really is the role… is to serve the heart, it’s the only role. We let go of our volatile toxins of carbon dioxide. Our drama, is nothing for the environment as long as we take care of the environment. If we don’t care take of the environment, we’re not going to get clean air. If you think about it philosophically, anybody listening to this. The molecule of air in your mouth, or in your nose, the moment it gotten comes in, it’s connected to you and it’s connected to the whole universe, right? It’s one big space.

Dr. Weitz:            Right.

Dr. Eliaz:              That’s the connection we have. Now we take air that comes into the lungs, the lung contract and it sends blood everywhere without discrimination. Aorta is a rigid artery. It can’t contract and expand. It send blood up, down, left, right. It’s downstream that we start playing monkey business who gets blood, who doesn’t get blood. And who does the heart nourishes first? It nourishes itself through the coronary artery. The beauty of this for me, wow. I mean, I’ve never heard this description until it came to my mind, I was meditating. The heart nourishes itself, in order to nourish other organs so it can contract, do its work. It nourishes itself is part of nourishing everybody. When our heart is open and we give love, compassion, nourishment to others, we can also give love, compassion, nourishment to ourselves.

That’s the healing of the Survival Paradox. But if we just want to love ourselves and focus on ourselves, it’s called narcissism, it’s very different. The heart is the only organ who knows itself after it finished its work. Think about it when it finished its work, in the gets the blood. It’s connected with the universe. It got oxygenated, it sends a blood all when it’s out of the heart, totally selflessly takes care of itself. This means that we have built-in to do this and that’s why certain meditation techniques, they take in suffering and transform into love and compassion. [Tonglin 00:46:45] is a classical meditation. It’s so easy to learn and so profound, because we are built to do it. We don’t have to experience… It’s who we are. That was the how it does.

We do it physiologically anyway, we just connect with it on a mental meditative level, emotional level, psychological level and suddenly we don’t have the same reactivity. When we do this, things change. That’s why there’s so many studies on the healing power of love and compassion. But the heart also has a greatest electromagnetic field in the body, a hundred times greater than the brain. The electromagnetic field of the heart is a few yards. Which means that we heart-to-heart connected. People around us, we are connected heart-to-heart, that’s why we can feel people around us. But more than this, the heart electromagnetic field is touching every cell in the body in every single second. This is what I call this, and is the topic of my next book, Open Heart Medicine.

When we open our heart, we connect with our infinite healing power. Because the essence of transforming the Survival Paradox, is recognizing the impermanent for people who are more [inaudible 00:48:10] illusory quality of our experience. If everything is changing all the time, then anything and everything is possible. That’s why one of my favorite saying that I know I probably told you before is, not everybody is going to be a miracle, but everybody can be a miracle, and that’s tapping into our infinite healing potential. That’s the transforming and freeing of the Survival Paradox. This is really based on a certain vision I had many years ago when I was in the mountains for months on my own, that gave it to me in a very esoteric way related to some Tibetan studies.  But then I realized, my God forget about this. This is practical, it’s who we are. We have this in each of us, because it’s all in our heart and it’s a life journey. I mean, I’m just a beginner myself. But it’s a journey and then I think as His Holiness Dalai Lama says, “There is no limit to love and compassion.” It always can grow and open and open, and that’s a different level of healing. That is beyond just physical healing, it’s beyond the physical disease. But when we put it together with blocking galectin-3, we’re changing our lifestyle with proper exercise. Then we get amazing physical benefits of course.

Dr. Weitz:            And of course, with respect to the heart. Galectin-3 is a major factor in heart failure, with which resulting in fibrosis and also plays a role in aortic stenosis.

Dr. Eliaz:              Huge and interesting, and you are really well versed in the Galactin-3, the literature. Galectin-3 plays a specific role in what we call ejection fraction preserved. In the worst heart failure, which is a one man’s. The heart doesn’t become too big, the heart becomes stiff, fibrotic. Why? Because galectin-3 drives fibrosis. But if you think about a fibrotic heart that doesn’t contract, there’s a beautiful song in Hebrew that was written about the Western Wall, the Wailing Wall of the Temple. It’s about the big stone. They said, there are stones, which are like a heart, and the heart of people which are like stone. So when we have a stony heart that doesn’t want to give, we get fibrotic. We get aortic stenosis, and I’ve seen patients like this. Where they are self focused, they can’t give. [inaudible 00:50:49] are not a ware that they can’t give. They will get fibrotic heart and when you start changing it, the heart will get better. That’s the beauty of the mind, body. It’s so intertwined, it’s like wow.

Dr. Weitz:            Right. So you’ve written about galectin-3 playing a role in Alzheimer’s disease and playing a role in the formation of amyloid plaquing.

Dr. Eliaz:              Right, a lot because the amyloid plaque is the Alzheimer plaque. The galectin-3 concentration is 20 fold compared to the normal in a central nervous system tissue in the microglia, the astrocytes, are driven to become inflammatory through galectin-3. The microglia are very similar to the macrophage in the body, they clean up the mess and they need to be there. But when they go out of control, just like in the body, then it affects. Rights, I discuss all of this in the book and I really want to emphasize. I mean, people will see this later on, but people are saying it today. During this one week of September 21 to 28 starting today, the eBook, The Kindle is available for only 99 cents, my publisher is making it available. Really, because my goal is just for people to just really… I’m really showing my heart in this book, so I put the time, I put the effort, I really want as many people to really read it and-

Dr. Weitz:            Have you talked to Dale Bredesen or some of the doctors in his group about incorporating this into their protocol for reversing Alzheimer’s?

Dr. Eliaz:              No, I was in touch with the Buck Institute a few years ago. But the guy who wanted to start the research left it.

Dr. Weitz:            Okay.

Dr. Eliaz:              But yes, of course there is… Now we realize that Alzheimer is a vascular metabolic disease. It really is, I mean it’s… I mean, I think about a dear relative of mine who had Alzheimer’s and she was getting better. She was taking a lot of vitamins, she was getting better but a family member of her got so upset at her and made her stop and she really deteriorated. [crosstalk 00:53:07].

Dr. Weitz:            Yeah. Medicine Now for the first time has published a study showing reversal of Alzheimer’s in 25 patients and how they’re getting ready to [inaudible 00:53:17].

Dr. Eliaz:              Absolutely. Alzheimer’s is a reversible disease. Big, absolutely. I mean, it’s not easy-

Dr. Weitz:            But only with functional medicine approach.

Dr. Eliaz:              Only with functional.

Dr. Weitz:            Because the conventional medical approach really has nothing to offer at this point in time.

Dr. Eliaz:              Yeah, right definitely.

Dr. Weitz:            [inaudible 00:53:36], perhaps you can tell us a story about how you developed this modified citrus pectin?

Dr. Eliaz:              Yeah. I’m a native of Israel and I’m 62 years old, It was 1971, and I was 12 years old and we took a walk to our neighbor, [Theuthan and Leoco 00:53:52]. Both of them had PhDs in organic chemistry, were the pioneers in the citrus industry in Israel. Israel in the early 20th century, all the way too late, was pretty much, most of the open land was citrus orchards, so they were experts. Then Ruth out of the blue, she turned to me and she say, “Isaac, one day they will find a cure for cancer from the citrus fruit.” It stuck in my mind and 24 years later when the first study and NCP came out with Avraham Raz, I called her. I told her, Ruth it’s Isaac. I’m calling from San Francisco, my mother got her number.  You probably don’t remember, I remember what you told me when you were 12 years old, and she put me in touch with the key pectin researchers in Europe and they helped me to develop modified citrus pectin, and since then I can say comfortably that modified citrus pectin, Pectasol have added tens of thousands if not hundreds of thousands of years of life to people. It’s really such a privilege to have the opportunity to make such a contribution. Really Ruth is the one who spiked this in my mind. But it’s really important. If I was caught in a box that it’s only cancer, I wouldn’t see the other indications that the sometimes I get emails from researchers. “Hey, you got to check these.” I don’t know, well guess what? We already published or we already discovered or yeah.

It’s a very growing field, but we don’t want to get lost in the details. In medicine, it’s easy to get lost in the details. Because we know so many details. It’s important to remember the big picture. The big picture is that Survival Paradox shortens our life. You want to know what is a proven anti aging treatment, blocking galectin-3 using modified citrus pectin. Because galectin-3 drives aging. Drives chronic diseases, there is no argument about it. You really understand how when we finish Survival Paradox, our longevity improved not only from a point of view of the length of time, but from the quality of our life.

Dr. Weitz:            Galectin-3 really should be part of a longevity program.

Dr. Eliaz:              Blocking galectin-3 absolutely. The first supplement you take, because it works in logistically with so many others.

Dr. Weitz:            Do we know if modified citrus pectin affects AMPK, or any of the-

Dr. Eliaz:              Of course, absolutely. Definitely it does. Of course, because galectin-3 blocks insulin receptor, shuts down AMPK and mTORC1 goes up. That’s why, but-

Dr. Weitz:            A similar way to Metformin?

Dr. Eliaz:              Yeah of course, but for me it works intracellularly. For example, it’s with a great combination, but from a natural product, I use MCP with Honokiol, because Honokiol will enhance AMPK, and block [ENTO1 00:56:53], and block AKP and block [HIF 00:56:56] I don’t have a diagram here and I think in the book, I took it out. It’s my favorite diagram, but I didn’t want to make the book to medical. It’s the oil factors that will block PDH, Pyruvate Dehydrogenase that will shut down normal metabolism in the mitochondria. Honokiol with MCP and we’ve demonstrated enhanced synergistic anti-inflammatory, antioxidant effect. We have multiple patents on this. We published a number of papers on this, and we at some point we’ll develop a newer inflammation product based on this combination.

Dr. Weitz:            Oh yeah. Definitely you should be testing that on rats or dogs.

Dr. Eliaz:              Yeah, we are. We’ve already published a number of papers on this one I think.

Dr. Weitz:            What about using MCP with berberine which is [inaudible 00:57:40].

Dr. Eliaz:              Oh yeah, of course. Berberine is very similar.

Dr. Weitz:            [inaudible 00:57:44].

Dr. Eliaz:              I prefer Honokiol because it is has a more wider range of benefit. It also changes glutamate into GABA, so it reduces excitatory effect, so it’s very relaxing. It has more of an ever inflammatory effect. It’s synergistic with practically every cancer treatment, because the same mechanism, so we use them together. MCP, Honokiol is a great combination for glioblastoma is for example, for brain cancers. Yeah, definitely.

Dr. Weitz:            Interesting. What would the dosage MCPB? Would that be 15 or 20?

Dr. Eliaz:              Yeah. No, it would be 15. If the galectin-3 is high, you can go up to 20. Then Honokiol, you can go up to one gram three times a day. The main side effect is diarrhea sometimes, so it stop and it goes away.

Dr. Weitz:            For galectin-3, what should be the target? What’s considered low? What’s considered high? What’s optimal, if I wanted to be on an optimal longevity program.

Dr. Eliaz:              Ideally, optimal will be eight to ten, eight to eleven. It’s lower now, because they are both platform which is what is used, give lower numbers. Again, it’s another problem, but it’s definitely. If you look at normal blood based on the BGM manual kit, they will say under 17.8 is normal, something under 22. If you look at the Framingham Offspring Study, 8,000 people with microalbuminuria already have a problem, the average is 10.9. The 20%, the 40 lower point quintiles, they were like nine or ten, compared to the highest one which was 15.6 only, three times all cause mortality in 12 years, three times.

Dr. Weitz:            Wow.

Dr. Eliaz:               It’s 15.6. Somebody will think it’s normal. Yeah, so basically, when it comes to modified citrus pectin, you should take it based on your condition. If you’re totally healthy, like you don’t have inflammatory condition or not a problem, and your galectin-3 is low, it’s at ten, eleven. Then you can take five grams a day. If you’re over 40, go up to 10. If your galectin-3 goes to above 14, you need a full dose already. Why? Because there’s more galectin-3 to handle. It’s not user, not user. Just more galectin-3, so you need more you MCP to actually block it.

Dr. Weitz:            Is there any benefits to recovering from a long term viral infection?

Dr. Eliaz:              Oh, yeah, because of course you want to get the post infectious fibrotic effect. Of course same with virus and with radiation, same with surgery. Same principle of course. You want the healing like-

Dr. Weitz:            So it’s like long term symptoms after a viral infection? This could be an important part of the protocol.

Dr. Eliaz:              Very important. It’s like I write about it in the book. There is this Buddhist concept of writing in water or birds flying in the sky, then it disappears, that’s how you want your healing. With no scarring, with no remnants. What causes the remnants, what causes the scarring is galectin-3. It drives the scarring process.

Dr. Weitz:            As a chiropractor, I treat many musculoskeletal [inaudible 01:01:01] like herniated discs and tendinitis. I’m assuming that galectin-3 is probably playing a role in those conditions and the modified citrus pectin.

Dr. Eliaz:              Absolutely, and you will see effect. The other supplement that is amazing for this chronic inflammation, and especially for dental health, almost a miracle is Padma Basic. Anybody with gingivitis, with root canals problem, with periodontitis, Padma Basic three twice a day.

Dr. Weitz:            What is it?

Dr. Eliaz:              Padma Basic. Padma basic is a Tibetan based herbal formula.

Dr. Weitz:            Okay.

Dr. Eliaz:              It’s really not concentrated in the herbs themselves, but it’s an approved drug in Europe since 1965 for circulatory problems.

Dr. Weitz:            Oh, okay.

Dr. Eliaz:              It’s very important during COVID times because it reduces inflammation. But the really amazing things, is dental problems. It’s insane. Nothing like it for dental problems. And of course, Honokiol and modified citrus pectin are very important for dental problems. And there’s much higher level of galectin-3 in the plaque, in periodontitis and so these are all important [inaudible 01:02:20].

Dr. Weitz:            Interesting. Some of the longevity, researchers are looking at periodontitis as sort of a marker of aging.

Dr. Eliaz:              Of course. I mean, I send every patient of mine gets an [inaudible 01:02:32] beam just to look at pockets of inflammation. It’s a much bigger problems than mercury in the teeth. Yeah, definitely and it will reduce it. Padma Basic, I mean all the three compound Padma Basic, modified citrus pectin and honokiol, but Padma Basic is insane. Of course to improve your circulation, open up. It has meta-analysis clinical trial, drugs don’t have it. But for the dental, I’ve just realized because of multiple patients recently. My God, the community needs to know this. We have something, they published a study on chronic pulpitis, which is really inflammation, infection of the root of the tooth where you need root canal, and 80% daily root canals, and pains went down in days. I’m seeing this clinically in patients.

Dr. Weitz:            Really?

Dr. Eliaz:              Yeah, and only three twice a day.

Dr. Weitz:            Wow.

Dr. Eliaz:              Amazing tuff there. Really a gift from nature, a gift from the Himalayas.

Dr. Weitz:            Oh, I’m going to have to look into that. That’s something that I’m not-

Dr. Eliaz:              Yeah, I’ll send you. Send me an email, I’ll send you the study.

Dr. Weitz:            Okay.

Dr. Eliaz:              Very cool, yeah.

Dr. Weitz:            Great.

Dr. Eliaz:              It regulates immune response with the cytokine storm, yeah.

Dr. Weitz:            Oh, cool, awesome. Okay thank you, Isaac.

Dr. Eliaz:              Thank you and for… Yeah, and everybody’s book is available on amazon.com, or you can go to survivalparadox.com. We have a really nice landing page with information and yeah again, we’re making it so affordable, the book. Because it has a really… It really has a unique message. I think it’s time to take our approach to medicine to in different vibrational level, tradition awareness level.

Dr. Weitz:            Yeah, it’s about time we start focusing on health and not just disease.

Dr. Eliaz:              Yeah, and beyond inflammation, what’s beyond inflammation.

Dr. Weitz:            Right.

Dr. Eliaz:              Thank you, I love talking to you. I’m looking forward for the next time.

Dr. Weitz:            Absolutely, thank you so much.

Dr. Eliaz:              Thank you, yeah. Bye, Ben.

Dr. Weitz:            Thank you for making it all the way through this episode of the Rational Wellness Podcast. If you enjoyed this podcast, please go to Apple Podcasts and give us a five star ratings and review, that way more people will be able to find this Rational Wellness Podcast when they’re searching for health podcasts. I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica Weitz Sports Chiropractic and Nutrition Clinic. If you’re interested, please call my office 310-395-3111 and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you and see you next week.

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Ryan Smith speaks about Measuring Biological Aging via Epigenetic Methylation with Dr. Ben Weitz at the Functional Medicine Discussion Group meeting on August 26, 2021.

[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

5:36  Epigenetic methylation.  DNA methylation is essentially inactivating of a gene transcription.  When a methyl group is placed on a particular gene, that gene typically gets turned off. This occurs especially at the CPG islands, which are the sections of our DNA when we have cytosine and guanine based pairs repeated over and over.  This process is related but separate from situations where you find out that patients have polymorphisms in the MTHFR and/or the COMT genes and who may require supplementation with methylated B vitamins like methylfolate and methyl B12.

10:30  While epigenetic methylation is used to measure aging, it is also being used for other things, including detecting cancer, including a new test known as Galleri from Grail, which is a liquid biopsy that is able to detect cancer very early, including at stage zero before it’s able to be found by any other method.  It can detect over 28 different types of cancer.

12:37  Ryan and the TruAge test are focused on using epigenetic methylation to measure biological aging. Dr. David Sinclair in his new Lifespan book talks about aging as a disease.  And to slow down and reverse aging we need to prevent cancer and other chronic diseases like heart disease and diabetes. Approximately 80% of adults in the US over age 65 have at least one chronic disease.  And if we reduce aging, then chronic disease risk will drop.  Prior to epigenetics (methylation clocks), telomere length has been validated as a way to measure biological aging, but it has low predictive capabilities. Epigenetics is both highly validated and highly predictive. The lower your biological age, the longer you are going to live.  70% of all cancers occur in people 65 and up.  For every one year you are older biologically, you increase your risk of getting cancer in the next six years by 6%.  If you are two years older biologically, you have a 12% increased risk of getting cancer in the next six years and you have 34% increased risk of dying of cancer in the next five years.  If we can reverse your biological age by seven years we can cut disease in half.  If we can slow biological aging by 20%, the US would save over $3 trillion dollars in healthcare spending.  We can also tell you how old your immune system, how many CD8 and CD4 T cells you have, how many granular sites you have. And if you reduce your aging rate, you can reduce all of these different aging phenotypes.  Aging should be treated as a disease.

44:12  Interventions to reverse aging.  While the first published intervention trial to reverse aging, the TRIIM trial (TRIIM stands for thymic rejuvenation and immunorestoration) by Dr. Fahy and others, used growth hormone, Metformin, DHEA, zinc, and vitamin D, most of the longevity researchers including Dr. Sinclair and Dr. Longo have found that lower growth hormone levels are associated with better aging.  Despite the benefits seen in this trial, the data does seem to show that higher growth hormone and IGF-1 levels are negative for longevity.  And data on Laron dwarfs show that they have a growth hormone deficiency and they tend to live longer.  Some of the recent data indicates that it may be DHEA that most consistently correlates with longevity of the three interventions in this trial.  When you look at Dr. Horvath’s original algorithm, which looks at 353 spots on the DHA over 80 of those spots are located at or near glucocorticoid receptor elements.  This means that the more cortisol you have, the more stress you have, the more it might impact your epigenetic aging and DHEA can mitigate the effects of cortisol.  Here is the TRIIM trial:  Reversal of epigenetic aging and immunosenescent trends in humans.

Ryan Smith is the co-creator and vice-president of TruDiagnostic which offers the TruAge test, which uses an epigenetic methylation clock to measure biological aging.

Dr. Ben Weitz is available for 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.

Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talked 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.

Thank you for joining our functional medicine discussion group meeting tonight on epigenetic methylation in aging and disease with Ryan Smith.

I want to thank our sponsor for this evening is Integrative Therapeutics, which is one of the few high quality professional brands of nutritional supplements that we carry in our office, super high quality, very innovative. I’m just going to mention a couple of their products. They have a specialized form of curcumin called Theracurmin. There’s been a fair amount of research on it. It’s a water dispersible. And for two capsules, you get the full dosage, which makes it a lot easier and more convenient than some of the other leading forms of absorbable curcumin.

Another one of their products is a product called Heartburn Advantage, which we use a lot for gut patients. And so this is a product that includes a natural prokinetic that improves motility of the gut, and also includes deglycyrrhized licorice and zinc carnosine for soothing and healing the lining of the gut. So it’s great for patients with reflux. And we also use it for SIBO patients.

Dr. Weitz:            Tonight, our topic is epigenetic methylation in aging and disease. I’m sure most of us know what epigenetics is, which is essentially, and Ryan will give us a much more detailed explanation. It’s a set of triggers and switches that turns our genes on or genes off. Put it another way, it’s the factors that result in whether our genes are expressed or not.  Methylation can be tracked and correlated with aging. And methylation clocks are what the latest research is showing us is the best way to measure biological aging as compared to chronological aging. And this is very applicable to those in the functional medicine community who are advising our patients in diet and lifestyle programs to promote longevity.

My goals for tonight are to learn about how to test for biological aging, how to interpret such testing and how to touch on some of the latest research on interventions to promote longevity. Ryan, this is Ryan Smith, co-creator and vice-president, TruDiagnostics or for the TruAge tests. Ryan, maybe, you can give us a little bit about your background.

Ryan:                    Yeah. Absolutely. So first and foremost, thanks so much for having me. I’m excited to talk tonight. I am always excited to talk about this topic and introduce it to new people, because I think it’s always something a little bit sci-fi, something a little bit different than sort of the clinical application that they probably know about methylation right now.  I definitely have a PowerPoint. I don’t know if you’d like me to show it or not. I’m happy to, but I can’t show it at the moment–I can’t present at the moment. And so it might be good if you can allow me to share it and maybe the host, I’d be happy to do it, but yeah,… 

Dr. Weitz:            Please mute yourself…. Okay. Okay, good. I guess we should be good.

Ryan:                   Excellent. Yeah. Again, thanks for having me. My background is a little bit diverse, biochemistry undergrad. I went to medical school at the University of Kentucky. Passed step one. Did really well, but got to the clinical stuff and just hated it. So shortly thereafter, we created a compounding pharmacy that sort of specialized in peptides and proteins called Tailor Made Compounding. We had a lot of success. But as we were doing new and innovative pharmaceuticals and molecules, one of the things I always wanted to know is how is this having an effect on the long run? How is it affecting health span, life span outside of the immediate benefits you might have from a day-to-day basis?  And so I’d always been really interested in this as a diagnostic when I first heard about it, particularly because it was able to predict things like death, predict things like the age of your body. And as we know, aging is the number one risk factor for all chronic disease and death.  And so knowing that was a modifiable factor and one that we could now manage was really, really exciting to me. And so, we decided to create TruDiagnostic because I saw there was a really big need in this epigenetic methylation space for really good clinical algorithms. And so we started this company and doing commercial test in July of 2020, and we’re over a year old now. We’ve tested over 12,000 patients, have one of the largest private epigenetic databases in the world and in some of the most robust testing algorithms in the world.  And so we’re really excited to talk about everything and go through and give an introduction into methylation. And so, yeah. So just to go ahead and get started, for those of you who aren’t familiar, I would love to just quickly go through epigenetic methylation. And here’s some of the things that I want to try and go over today, right? What is it? How can you use it clinically? How does methylation relate to aging. And then, how can you use these algorithms in your current practice?

And I always like to start off with this quote, but it says” Five to 10 years from now, the health system that doesn’t use this data to help improve their medical delivery is going to be deemed archaic.” That’s how quickly that this is coming, right? This is even anticipated by some people to overtake blood testing in the next 20 years. And so this is something that if you don’t know about it yet, it will affect your clinical practice. It’ll affect your clinical practice in the next five to 10 years greatly. And that is a great thing.  And this is some of the mission and goals of us at TruDiagnostic, but we really want to improve patients’ lives by helping them make the right decision at the right time and by leveraging this new biomarker to be able to make those decisions. And so I think you gave a great explanation of what epigenetics is, right? It is every cell in your body has the exact same DNA structure, but obviously, the genes which are turned on and turned off in your skin are greatly different than the genes that are turned on and turned off in your heart.

And in the way that they do those sort of changes of turning things on or off are through these types of epigenetic modifications. For the purposes of what we’re going to talk about today, we’re really going to talk about DNA methylation. And DNA methylation is really thought to be that inactivating of a gene transcription. So usually, whenever it’s placed on a particular gene, that gene is turned off, whereas histone modifications like acetylation, on the other hand, are really turning on genes. And so we’re able to measure these things in our cells on our DNA, and then correlate them to outcomes.

And so just to give a little bit more terminology, one of the big terminology points I’ll use often are called CpGs. And these are cytosine and guanine islands where those sort of base pairs are repeated and repeated. That is actually where we’re looking for most of these methylation-related signatures. And so you might hear me talk about that quite a bit, and that’ll be a term that we use because that’s what we’re really measuring. Is methylation on or off those genes. And this is a process by which we methylate our DNA. We attach those methylate groups to cytosines in the DNA.

And to do that, we use a supplement actually that a lot of you might be familiar with, SAMe or the S-adenosylmethionine. So many people, you might be familiar with using it to help treat depression or osteoarthritis or many other things. And I think it’s also important here to separate this from a methylation that you might have already used clinically things like, for instance, MTHFR or COMT genes. It’s sort of a similar biochemical process, but how we’re sort of looking at these and addressing them are completely different.  And so I think it’s also important to say that so that the two separate processes and I think it’s important to make that distinction. And so whenever we talk about this, it’s important to know that this is a very, very new biomarker, really the first time-

Dr. Weitz:              Are those two processes similar? For example, is it the case that if you take a lot of methyl B vitamins, folate, and B12 that you can increase the methylation of the DNA?

Ryan:                     Yeah. Absolutely. They are connected. For instance, we know that some people who have polymorphisms in that MTHFR gene have actually worse biological ages because of it. And so they’re related, but the biochemical process of if you’re able to have the co-factors to methylate will affect the DNA methylation, but the DNA methylation itself is sort of the cause, the root cause I would say, of what genes are turned on and off. And therefore, what we’re expressing in our DNA.  And so they’re related, and they affect each other, but probably not the way that you’re thinking clinically where supplementation with B vitamins or 5-methylfolate or CME are going to have the same effects that you would imagine would be a good thing. And so they’re related processes, but still at the same time, very vastly different from a clinical approach.

And I think we can even sort of talk about that when we talk about some of the treatments, which were to reversing the aging process. And again, not to bury the lead, that is what we can do, is we can. Now that we have an objective way to manage this aging process, we do know ways to sort of to change it. And so before I go into the aging aspect, which is, I think, probably the most exciting, I also want to go talk about some of the other things that epigenetic methylation is used in clinically because although aging is a big part of it, it goes way beyond that.  And so many of you might be familiar with a relatively new test, just came out in the past 10 weeks, called Galleri from GRAIL who was just bought by a woman. And this is a test much like IVG [inaudible 00:10:50] if you’re familiar with those in the past. It’s called the liquid biopsy, which is able to detect a cancer at very, very early stages, even stage zero before it’s able to be found by any other method.  And this is probably the biggest growing area of sort of the commercial market, because cancer is obviously so prevalent. And you want to catch it early so that you can then treat it. And this test can detect over 28 different types of cancers with a single blood test. And so that is a very exciting development and probably one of the biggest areas of epigenetics.  In addition to that, there’s a lot of new drugs, which are being approved that treat different types of things, particularly cancer via epigenetic mechanisms where they can sort of take a drug to turn things on or off from your DNA expression. And so this is another big area as well. And again, I won’t go over it a lot today, but you’ll probably see a lot of this in the future, particularly the GRAIL Galleri test is now becoming widely popular, even though it was only released a few weeks ago.

And so those are other applications which are really, really exciting, but I just want to again stress that this is a new biomarker. Being able to actually get the information whether it’s part of your DNA is or is not methylated is a relatively new thing. Really in 2009, we only could read right around 80,000 of those markers at a time.  And there’s over 26 million for every cell in your body. Even towards 2017, we only had right around 450. Now sort of the baseline for most standard research testing is 850 to 900,000. And that is what we’re doing here. So we’re now finally able to read this data at a large scale. And that’s what sort of making all these developments so much more relevant and what will continue to sort of change medicine.  And so the real application for this epigenetic testing that I want to talk about today is biological age measurement. And many of you might be familiar with this sort of renaissance in the aging community. I always like to point this book out, Dr. David Sinclair’s Lifespan book, because in it, he sort of talks about this idea of aging as a disease and sort of bringing the light to this whole idea of treating aging before it happens.  We talk about those things like cancer. But cancer, one of the biggest risk factors for cancer is actually age. And so with those liquid biopsies, we’re trying to detect it. But if we can address age, maybe we can even prevent cancer from happening or prevent all of those age-related diseases, which is every chronic disease, diabetes, heart attack, stroke, you name. It is usually an age-related disease.  And so even though the national community is picking up on this with now the World Health Organization has added an ICD-10 extension code for age where you can sort of say that these diseases are caused by age. And even things like Alzheimer’s and hypertension weren’t even considered diseases in and of themselves at one point in time. They were considered sort of a sequelae of aging.  And so we know that aging is an important and really at TruDiagnostics, we definitely think that aging is a disease. And some of these statistics even show that 80% of adults have at least one chronic disease if they’re over 65. And you can see that the percentage of population with these chronic diseases over 65 are prevalent. And so we know this. And as I mentioned with cancer, by the time you reach 60, your risk of getting cancer doubles from when you were 50.  70% of all cancers occur in people 65 and up. And so again, aging is a disease and definitely sort of treated like it. But the good news though is that if we’re able to treat aging, we can have massive impacts on population level health.

So for instance, if we’re able to reverse your biological age, so the age of your body, by seven years, we would be able to cut a disease in half. 50% of the people in the world would no longer be sick. In addition to that, if biological aging could just be slowed by 20%, the US would save over $3 trillion in healthcare spending. And so what we are really trying to do is quantify the aging process, let everyone know where they’re at, so they can make the changes to reverse that aging process and improve their health and prevent all of these health outcomes. And we always say, “You can’t manage what you can’t measure.” So what we’re trying to do is give an appropriate way to measure that.  And so when it comes to aging, I also think it’s important to say why chronological age is not a very good measure. Chronological age is obviously everyone knows their chronological age. But everyone probably also knows people in their 70s who looked like they were in their 50s, and people in their 40s who looked like they’re in their 80s. People all age at different rates and that’s this phenotypic variation where depending on how well you take care of yourself, you can change the way that you age.  And so chronological age is still the biggest risk factor for chronic disease. But biological age can be even more predictive and even a bigger risk factor. And so biological age, they’ve been trying to find a way to look at this for a long time way better than chronological age.

And there’ve been a lot of different postulations for the best measurement. These are some of the criteria that American Federation for Aging Research created. But beyond that, most of you are probably familiar with what has been clinically used for the past couple of years, really the past decade, for the best measurement of biological age, which is typically telomeres. And so I won’t go into that a lot. But obviously, most of you are familiar with this, right? Those in caps on your DNA that when replicating solely gets shorter and shorter and shorter and shorter.

And when they do, that’s correlated to this aging process. And so this has sort of been the standard for a long, long time. But it’s probably not the best. And the reason being is that I always love to show this sort of summary from 2017, I should say, which compared all of the different ways to measure biological age. And telomeres, although it’s been the standard methylation related biological age testing is now becoming much more accurate and much more predictive.

One of the big problems with telomeres is that even though it is correlated to age, if you have low telomere length, it doesn’t necessarily mean you’re going to have any type of age-related outcome. It’s sorts of, as this study puts it, briefly telomere length is extensively validated, but it has low predictive capabilities. And really, what we’re trying to do with this aging is to predict the outcomes of disease.  And so telomeres have never been the best. And I always like to show this as well, where this hazard ratio, telomere really definitely has the most studies done on it. But it’s by far the least predictive if you look on this graph. It has the lowest hazard ratio, whereas epigenetics is highly predictive and highly validated, which sort of shows us it is the best way to measure age.

And so, that’s what we do. We use this biological age to give you, essentially, we test your DNA, and we give you an age, how old your body is. And this is a process which is relatively complicated. This is actually the process which we do it. We sort of collect just a few drops of blood. We can do it with just a fingerstick blood test, where then we extract the DNA. And then, we sort of look at all of the different copies at all of those CpG spots. We look at number 900,000 locations to really get an idea of is that location methylated or is it not.  And we sort of sum up all of that to get a percentage of methylation at each location in your genome. And we measure, as I mentioned, a lot of spots. And we’re getting a lot of data. This is sort of what we see at every different location that we look at over 900,000. And so what we essentially get at the top at each of those 900,000 locations is a percentage of methylation. Out of all the copies of your DNA, what was the percentage that was methylated?  So if we’re looking at, for instance, we were talking about maybe an MTHFR-related gene, we can say, “How much of those are methylated?” 80%, 20%, whatever it might be. And then, we plug it into these mathematical-derived algorithms, which are listed below. This is actually one of the first ever biological-age algorithms that came out from Dr. Steve Horvath at UCLA who’s really the worldwide expert in this.  And what did this is able to do is to take those percentages and then to turn it into something that’s clinically useful like age. And these things have been created in sort of another thing. So we’ve talked about how the bio-marker is really new. And really, we now are the first time we’re able to look at it at scale. But the other big development is computer learning and artificial intelligence, where we’re able to use these really large datasets and turn it over to computer for it to tell us these insights. And so that’s exactly how these clocks are created. We sort of train this dataset and these artificial intelligence algorithms to give us a mathematical way to predict an outcome, in this case, age.

And so just to give a little bit of history, the first of these clocks came out in 2013, really the first really accurate clocks. And the first clocks were trained to predict chronologic age. And so the first time that they were used was actually not in relationship to medicine at all. It was used in relationship to things like crime scene investigations, where they would be able to tell how old someone was at a crime scene or to date refugees and see if they were over or under 18 and therefore eligible for asylum.  And so they were used for things way before they were used clinically because the first clocks were just trained to output chronologic age, so, trying to predict your age. And as I mentioned before, chronological age is not the best metric. And honestly, it’s not great to have a test score because if you really want to know clinically how old someone is, you can usually just ask, right? So the second generation clocks, as they call them, started to train against something a little bit different, which was those age-related outcomes, all of those diseases, which are associated with age.  And as a result, they created these algorithms, which were incredibly predictive for age outcomes. And beyond that, they even train them to predict things like death. In the case of GrimAge from this graphic with Dr. Horvath where he’s actually able to predict when you might die, very, very accurately.

And so the idea is that these clocks can be trained to predict just about any outcome. If you want to train it to predict how fast you might run a mile or predict how much hair you might have in your 50s, these things can be trained for that if you have enough data. And so I’ve included some of these things for you to look at, and also the difference between those chronologically trained clocks, the first-generation and the biologically age clocks, the second generation.

But overall, I think that the one takeaway from this is that the lower age you have biologically, the better you are. You’re going to live longer. You’re going to have a better health span. And there are many classical examples of this. One of my favorites to mention is in the instance of cancer, where for every one year that you are older biologically, you would increase your risk of dying or getting cancer within the next six years by 6%.  So for someone who’s two years older, biologically, they might be 50 chronologically and 52 biologically. They’d have a six… or sorry, 12% increased risk of cancer over the course of the next three years. And then, they would have essentially a 34% increased risk of dying of cancer over the next seven years… Five years. Sorry. So again, these things have massive impacts on to our risks. And so, we really want to be able to treat this as a disease and to really measure it.

But even since then, this is a really, really fast area of growth. And so just to show you, so all of the things that we already can do now, we can do a lot more than that. So we can obviously tell you your biological age. But we can also tell you how old your immune system is. We can tell you what your immune cell subsets are, how many CD8 T cells you have, how many CD4 T cells do you have? How many granular sites you have? We can tell you your telomere length, actually, in a way that’s more accurate and more predictive than traditional telomeres length measurements. And we can tell you your instantaneous rate of aging. At this moment, how fast are you aging?  And so all of these things can be used clinically, because if you reduce the aging rate, reduce the aging process, you can reduce all of these different aging phenotypes. And that really is the power. And so that is a little bit of a history. But I also want to talk about how [crosstalk 00:23:02].

Dr. Weitz:            Are you going to go into more detail on these? And if not-

Ryan:                   Yeah.

Dr. Weitz:            Yeah. Okay, good.

Ryan:                   Absolutely. I definitely want you to know. I know that you’ve obviously had some experience, so we’d love to, obviously, for you to guide me as well. But I want to talk about sort of how it’s used clinically. What type of results do you get whenever you run this testing? And then also, what’s a good result? What’s a bad result? And what can we do about it? And so I will go into that.  This is sort of our first report. This is the first one we ever did. And this is an interesting report. And you can see on the left, it gives you your biologic age versus your chronologic age. It gives you where you stand out in the population. And this is actually a very big report. It’s over 78 pages because it provides a lot of context. One of the things that we don’t want patients to do is to get scared, right?

Talking about the biggest risk factor for all of their age, and the fact that everyone knows where they should be at, right? If someone comes back older, they oftentimes get scared. And one of the things that we try and do is add context for that value. What are some of the things that might’ve increased your score at baseline, decrease your score at baseline or up to 40% of this metric is heritable.  And so some of it is within your control, and some of it hasn’t been. And so we try and give some background to those things to change it. But what I really want to focus on today is even some of those other impacts. Clinically, my favorite aging algorithm is what I want to stress the most today, which is this probably the introduction to this. Do you need a pace of aging algorithm metric?  And so this is my favorite. It’s actually considered the third generation algorithm. So it was recently created actually even in 2021 of this year. And what this sort of reads out to you is an instantaneous rate of aging. So it takes a look at you right now and says, “How many biological years per year are you aging?” It’s like a speedometer for your aging.  And one of the reasons this is so great is because it separates what you’ve done in the past versus what you’re doing now. So for somebody who’s lived a lifestyle that might’ve been stressful or unhealthy, you can still get an idea of what behaviors you’re doing right now, and then how to change it. You and I both might take Metformin. But my response might be significantly different from yours. And this allows us to do that personalized medicine to see sort of how we’re changing.

But I also want to go into how this metric was created and how predictive it is. And so this algorithm will never, ever be replicated because of how it was created. The study to create this algorithm started in New Zealand in 1975. And it started with over a thousand three-year-old children. Sorry. And so over a thousand three-year-old children.  And the idea was that they were going to measure across the lifespans of these children their aging rates. And so Duke actually propose this. And the National Institute of Aging actually said “We’re not going to fund you because if you do detect a rate of aging, it will not be significant to these health outcomes.” However, it ended up being very, very significant. And this is just one of the ways we’d like to demonstrate it.  So as of 2019, all of these patients were now 45 years of age. So they tracked them since three to age 45. And every year, twice a year, they took all of the age-related biomarkers you can imagine. They did everything from telomeres length to MRIs of the brain, to retinal imaging scans, to dental imaging scans. They did DEXA body composition scans. They did every type of age-related metric you can imagine.

One of the other things they did was facial aging. And so these people you see on the screen, they’re all the same age. They’re chronologically all age 45. But even on the outset, how their faces look changes due to the rates of aging. You can see on the left, there’s the slowest aging members of the cohort. And on the right, the fastest aging members of the cohort. Again, all of those people are age 45. But it looks like there’s 20 years of difference between those two people, those two groups.  And in fact, there is because they’re aging at different rates. They’re biologically different ages. And so this is just one of the ways that we can sort of show it. But there’s many other ways as well. Particularly, we do believe that actually aging occurs early in life. And that leads us to all of these types of disease, disability, and frailty.

Here are some really good examples. So if you look at the bottom, the X axis, you can see that we plot the pace of aging against the scores on these testing. And as you can see, the faster that you age, the worse you perform on your balance testing. And not just balance, but also on grip strength. And this also holds up things like sarcopenia and body composition. The faster you age, the worse your body count and the worst your balance, the worst your physical performance, the worst, actually your cognitive decline, right?  So the faster you age, really the more IQ points you will lose, the slower that you’ll process that mental speed. And again, all of these things that I’m reporting on now are things that are actually quality of life metrics, health span, not just lifespan. And I think that that’s important to note as well. When we treat aging as a disease, we don’t have to think about living a long time and being super unhappy while we’re doing it.

We also get to think about how we improve our quality of life. And those things are not sort of mutually exclusive. So, if we improve our rates of aging, we improve the appearance of our base. We improve our risk for Alzheimer’s, cognitive disease, grip strength, body composition, physical function measurements. This again is just an example of the differences in facial aging appearances.  It also affects our brain, like, with things like cortical thickness and surface area. And so this is one of my favorite algorithms because it is the most predictive. And you can really take a test now. Take a test in really eight weeks after you implement some type of therapy to see if that therapy is working for you.

And so the goal with this whole algorithm is really to keep that biological aging rate, that rate of aging below one. You want to be aging less than one biological year for every chronological year, because that means you’re essentially aging in reverse, right? If for every one year that you lived, you’re going to be younger sort of biologically.  And even if you’re slightly above one, this carries heavy risk. So, for instance, even if you’re aging at a rate of 1.01 biological years per year, you would increase your risk of death in the next seven years by 56% and increase your risk of a chronic disease in the next seven years by 54%. And those are incredibly high risks. And so again, the idea is we want to treat aging before it happens and really start with a lot of these procedures.

And so a lot of those questions that might come from this is what do I do about it? And quite frankly, that’s one of the hardest questions to answer because this is such a new diagnostic. With that being said though, we’re finding out ways to reverse this process all the time. One of the ways that we know reverse this process is actually caloric restriction.  And so this is a good example of a sort of data from the calorie trial. The calorie trial had sort of two treatment groups, which was a 20% caloric restriction group who basically added a calorie deficit every day for two years. And they were on the right. And you can see their change in biological age was less than half a year, over two years compared to the group who did not do caloric restriction, who aged anywhere from really one year to over two years.  And so we know that caloric restriction is absolutely one of the things that changes this, which probably is intuitive for anyone who’s been paying some attention to things like ProLon and Fasting Mimicking Diet and caloric restriction. And so that is absolutely one of the things that we know can change. But we know a lot about these other metrics as well. And so before I go on to maybe some of the other things we can tell and the other algorithms we can learn, do you think that there’s anything else I might be missing to introduce this topic as a whole?

Dr. Weitz:            No. I mean it’s a vast topic, and there’s tons of things that… I have tons of questions. But I’m going to hold them back till I see exactly where you’re going with this.

Ryan:                   Perfect. Yeah. No. I think the biggest thing is that when you were approaching this from a clinician standpoint, you want to encourage everyone to get these metrics as low as possible. But the younger you are, the better you’re going to live, the longer you’re going to live. And so that’s sort of the idea. But the other idea is that methylation can tell you a lot more things than just your age.  One of the things it can tell you is actually telomere length. And so, via the same mechanism of DNA methylation, we can actually predict telomere length. And again, the correlation for telomeres length to age, it has an R squared value of around 0.35 at a maximum whereas the correlation for this measurement is double that with age. So it’s more highly correlated to age. But in addition to that, it’s much more predictive of outcomes. It’s better at predicting time to death. It’s better to predict time to coronary heart disease and time to congestive heart failure. So in addition to all the other reports we do, we’re actually even able to look at telomere length and predict that as well.

Dr. Weitz:            And if methylation clock is a better predictor, why do we care about telomere length?

Ryan:                   It’s a very good question. And the answer is you probably don’t. But with that being said, it does capture a different part of aging than just the biological aging process we get through methylation. So, I actually just did a presentation about this before this. And one of the things I like to say is that by combining all of these things together, you can get an idea. You can actually explain more of the variance between phenotypic age. So you can sort of explain why someone might age quicker than someone else.  And so it’s an important feature. It’s still one of those hallmarks of aging. But in terms of its predictive capability, these biological age markers, these age clocks tend to be a little bit better than telomeres length completely. That’s a definitely a good question. But again, methylation can tell you just about anything you want, if you have the right data.

And so one of the things we actually look at is the immune system. So we have these things called deconvolution methods, where we essentially are able to predict the types of cells that we actually see in your testing. And so what that looks like for us on its output is we actually read these, if you can even see. I know it’s small texts. We’re actually able to tell you your percentage of lymphocytes, neutrophils, granulocytes. And also, we sort of culminate with this thing called the CD4 to CD8 ratio, which is that ratio of T-cells, which can be incredibly informative about your health status or immune health status.  And for this, you want that range to right one and four. If it’s under one, that means you might have some type of immunosuppression. So we’ve diagnosed things like HIV or chronic lymphocytic leukemia by seeing CD4 to CD8 ratios less than one. We’ve also been able to diagnose hyperreactivity events like auto-immune disease with CD4 ratios above four, which might signal a sort of a reactive immune system.

And so we can learn a lot about your immune system. And it just to sort of show you, there are many, many diseases which are associated with CD4 to CD8 ratios below one. And so that’s what we’re able to do. We’re actually able to use these sort of extrinsic gauge reports to get the age of your immune system but also sort of the overall health of your immune system. And this is obviously something that is very important as we consider COVID-19 or this pandemic where our immune response can greatly affect how much at risk we are.  And again, aging is a part of the immune process. It’s why as we get older and undergo that immunosenescence process, we have the worst immune systems, which is why older individuals are recommended for the vaccine first, because they’re at highest risk.  And so again, this is that idea, the thought process that aging affects all of our risks of all of these other diseases. And so this whole picture together, we can start to say, “How old is your body? How old is your immune system? How well is your immune system functioning?” How is your instantaneous pace of aging? And then, once we get that idea, we can sort of all compete with ourselves to get this as low as possible.

But I should also mention methylation in the case of what we already talked about it in terms of cancer diagnostics, but even beyond that, we can find out insights from low-site specific report. I mean, so this is where we look at individual areas for different disease categories. So we can actually even predict diabetes up to seven years earlier than fasting insulin and HBA-1C.  And so this can be a really early diagnostic to say, “Hey. Should I put my patient on some type of interventional treatment, something just a diet or maybe it’s Metformin, or maybe it’s a GLP-1 or an SGL2 inhibitor.” So the idea is you can even learn these things much like detecting stage zero cancer before you can detect it anywhere else. We can actually detect insulin resistance and diabetes risk before we can in any other metric. And so that’s exciting as well. We can actually-

Dr. Weitz:            Is that part of the TruAge report? Is that just-

Ryan:                   It is. Yeah. So already, we’re able to report out your risk of becoming diabetic. And really, we look at two different markers. If you’re in the risk range for both of those, then, we would highly recommend that you take some type of intervention to prevent the onset of diabetes. Unfortunately, it’s a very, very, I would say, specific test. But it’s not always the most sensitive, meaning that some people who have type-2 diabetes might read as no additional risk. But if you do read additional risk, that means you’re almost certainly likely to do that if you don’t have any other outcomes.  It’s not just diabetes. It also we can do it with obesity. And I’ll sort of fly through these because I want to spend as much time as possible sort of just discussing. But we can actually even predict if you’re likely to become obese. We can predict if you’re likely to lose weight with caloric restriction. We already talked about caloric restriction being great for the aging process. But a lot of patients also want to lose weight with it to improve their body composition. We can actually tell you if you’re going to, before you even do it. We can actually tell you how much you’ve smoked-

Dr. Weitz:            Ryan, is there an intervention if you find out that you have certain genes that are playing a role in while you’re obese? Can you either methylate or undermethylate them? Is there some way to have that happen?

Ryan:                   Unfortunately, the answer is almost certainly yes. But unfortunately, we don’t know yet. And that goes to the biggest disadvantage for this testing is that we’re not sure what interventions are going to change this yet. But we’re very, very quickly learning. There are new studies published about this every week with interventions. And so right now, we, 100%, know ways to reverse your aging. We also know ways… or I should say behaviors, which are correlated with changing those other types of reporting.  But we don’t know about particular interventions to change that risk of obesity or, I should say diabetes yet. But the idea is that they’re already great interventions to change both where your diet, exercise, nutrition, all those things and knowing that you’re at risk you can then make those changes a little bit ahead of time. But that also brings up a great idea, which is that what comes first, the behavior or the outcome?

It’s sort the chicken or the egg thing. And that’s the other great thing about the methylation marks in your DNA. It also presents a history of where you’ve been or what you’ve done your entire life. So we can actually look at, what they call, this exposome. So sort of the history of exposures that are actually found in your DNA, we can actually tell you how much you’ve smoked across your entire lifetime. We can tell you if you’re a former, never, or current smoker. We can actually do the same thing with drinking. We can tell you how much alcohol you’re currently drinking. Are you doing a moderate, mild, or a heavy amounts of alcohol?

And we can do that with more and more things as well. We can actually even predict your response to the medication. So, we can do pharmacoepigenetics. We can, for instance, predict if you’re likely to respond to Metformin from an HbA1c. Are you going to actually reduce your HbA1c or are you likely to have side effects?

In this particular study that we now have an algorithm that predicts if you’re likely to respond to Metformin, or if you’re likely to have those side effects. And for those patients who we know, I would say are, at risk, we might then not suggest Metformin. We might go to another type of intervention. And that’s just the beginning of what will happen.

And as I mentioned with the exposome as well, I wanted to mention we can actually tell you how much mold you’ve been exposed to over the course of your entire lifetime. We can tell you how much lead, mercury, arsenic, plastic, all of these environmental sort of toxins, we can actually see in your DNA. We actually just did a study on COVID-19, where now we don’t even need to take your antibodies to tell you if you’ve had COVID-19. We can see it in your methylation signals.

And so those things are all, I think, very, very exciting. And it leads to this idea of how do we change it, which is sort of found in this sort of diagram where we know all the dietary and societal things, which might increase or decrease the different types of aging processes. And I won’t go into intrinsic versus extrinsic epigenetic age. But it’s another way to even know more about your entire system.

And so these are all the things that we can develop with methylation already. Eventually, it will be one test that reads all of these different metrics. It’s probably a test that can read out your protein levels in your blood, your micronutrient levels in your blood, your hormone levels in your blood. So really, you can do almost all of the testing that you would want to do clinically with one test, if you have enough data and the correlations are tight enough.

And so that is really what we’re hoping for. But I think that the bigger picture is that although this platform is really exciting, being able to treat and quantify aging is even more exciting because you’re able to then prevent the biggest risk factor for all chronic disease and death. And that’s really what we’re trying to do. And so to work with us, it’s really easy to do again, you just order a kit from us. You take a few drops of blood from your finger. You send it back to us. And within two weeks, we give you all of these different reports. And so always happy to talk about that a little bit more. But would love to answer any questions. I know I went through that very, very quickly. And there’s a lot of information. But I’d be happy to answer any questions.

Dr. Weitz:            Can you discuss more about the immune findings and what does that tell us? And how does that help us with our patients?

Ryan:                   Yeah, definitely. So the immune system obviously is highly connected to aging in general. But these immunity convolution methods are essentially like doing flow cytometry testing on your patients to see what percentages of cells they have and how well their immune system is functioning. And so the CD4 to CD8 ratio is just the start. But with that, you can be able to tell if your patients have sort of immunosuppresses or if they have a hyperreactive immune system.

And so what that can generally tell you is, unfortunately, you might need to do some followup testing, right? You might need to say, “Oh, hey, if we see this low CD4 to CD8 ratio, we might want to do some other follow-up testing for things that might decrease the immune response, like, cancer, like HIV, some of those other things, or if you see a hyper-reactivity, you might say, “Hey, I want to start getting some metrics on, if they’re having an auto immune response.” I might want their ANA. I might want some of those other inflammation markers to see if they’re having inflammation.

And so it’s sort of like, I would say, an overall view of how well your immune system is functioning. But we also are able to read the age of your immune system, right? Immunosenescence is a big problem and one that can be helped by taking things to activate the immune system. But we give you the age of your immune system through that extrinsic age measurement, which is able to use a sort of population level data to say where your immune system is in the course of the lifespan.

Dr. Weitz:            Do these results correlate with senescent T cells?

Ryan:                   So, great question. Absolutely great question. And the answer is yes. So, recently, there was a great paper actually published this year from Rutgers University by Dr. Herbig which was really one of the first ways that they sort of quantified senescent T cells across a lifespan. And we’re hoping that we can then create an epigenetic deconvolution method to predict senescent cells. We actually just wrote our APR’s application to the National Science Foundation a week ago. And so that is absolutely something we’re doing, is we’re helping to quantify senescent cell burden with this testing. And we think we definitely can.

Dr. Weitz:            In terms of interventions to reverse the aging process, let’s go into some of that. The first question I have is there seems to be a little bit of a dichotomy between some of research right now. On the one hand, the first intervention that was actually been shown to reverse aging was the TRIIM trial by Dr. Fahy and others. And it used an intervention of growth hormone, Metformin, DHEA, zinc, and vitamin D. And so the thing I want to focus on is the growth hormone component.  And so, the concept is that as we get older, we tend to lose function. We tend to lose muscle. We lose bone. We have less mobility, and that definitely affects quality of life and even biological aging. And that all makes sense that growth hormone would be beneficial except that everybody, including Dr. Sinclair and Dr. Longo, and a lot of the top people doing research on longevity right now are saying that you want lower growth hormone levels. And specifically, they’re looking at IGF-1 levels, which my understanding is tracks with growth hormone. And so therefore, they’re recommending lower protein levels because they say that that leads to lower cancer levels.

Ryan:                   Yeah. So, absolutely great question. And there’s, again, a lot of conflicting viewpoints here. But I will say that for years and years and years, growth hormone and IGF-1 levels have been correlated to shorter lifespans.  And so there is a good body of data on that looking at even Laron dwarfs who have this growth hormone deficiency and they tend to live longer.  And so with that being said, the first trial was looking, that Metformin growth hormone, DHEA trial, that TRIIM trial was set up. Actually, TRIIM stands for thymic rejuvenation and immunorestoration. So the whole thought process, I think there, was using some of [inaudible 00:46:41] work to rejuvenate the immune system, particularly by rejuvenating the thymus.  And they thought that they could do that through growth hormone. And so that was why they chose growth hormone as the main product. And then they started thinking, “How can we reduce the insulin side effects, the insulin resistant side effects that typically come with growth hormone?” And that’s why they included the DHEA and Metformin.

And so the idea there was that they’re going to regenerate thymus, and they absolutely did. Over the course of that one year and a half year, they were able to sort of improve that thymic fat-free fraction, improve lymphocyte to monocyte ratios. They really did enhance the immune system. And then also, they did see improvements in biological aging.  However, if you were to talk to Dr. Horvath who was also an author on that paper, he would sort of tell you now that the data show that, again, higher growth hormone, higher IGF-1 actually do correspond to lower… Or actually, the higher biological agents.  And so it is looking like the more data that we have that maybe growth hormone is not reversing the age like it should. And so actually in our own trials, we can actually see that we see something similar where growth hormone might not be a super positive effect. And so that leads us to ask questions about Metformin and growth hormone, or it’s just Metformin and DHEA. And in our studies, we actually don’t even see that big of a change with Metformin, which is unfortunate because we’re really big proponents of Metformin was really on track to be one of the first drugs approved for anti-aging benefits.

So for us not to see a change in epigenetic age is a little bit disappointing. But one of the things we do see a change and a substantial change with is DHEA. DHEA was sort of an afterthought and I think that drug cocktail. But it seems to be one of the things that’s best to reversing that epigenetic aging process in our datasets. And one of the hypothesized reasons for that is due to the impact of stress on the epigenomes or on this epigenetic aging process of Dr. Horvath’s original algorithm, 353 spots in that original algorithm.  Over 80 of those spots are located at or near glucocorticoid receptor elements, meaning that the more cortisol you have, the more stress you have, the more it might impact your epigenetic aging and DHEA can mitigate the effects of cortisol. And so out of all of those three drugs, we are actually thinking that DHEA is having the best effect. But also Greg Fahy and Intervene Immune and the Clock Foundation are actually now expanding that trial to the TRIIM-X trial, where in the first trial, they only had nine patients. And they’re hoping to, I think now, it’s expanded to 50 or a hundred.  And so hopefully with that improved dataset, we’ll be able to learn a little bit more. But it was a great question. I think the growth hormone might have given us some unfortunate results in that TRIIM trial. There may be not indicative of its overall effect on longevity.

Dr. Weitz:            Let’s see. So with respect to DHEA being beneficial for longevity because it counters cortisol, what about other methods that functional medicine practitioners use to mitigate cortisol, including lifestyle factors, focusing on sleep, breathing, a series of things? What about supplements that modulate adrenal function like phosphatidylserine and adaptogenic herbs? Would those have a similar effect as DHEA?

Ryan:                     So we don’t know. We’re not even sure that DHEA is having an effect through cortisol mitigation. We think that is. But we’re not certain. And so, unfortunately, we don’t have a lot of that data sets. Just look at people who’ve taken this testing and then essentially done these interventions and taking the test and again. In fact, they’ve only been applied interventional trials published.  Actually, to answer that question though, one of the most recent trials published was actually the work I think that you and I have already talked about by Dr. Kara Fitzgerald which actually did look at some of those adaptogens as well as a probiotic and did things like sort of mindfulness and stress management as a way to maybe even impact that change.  And although her trial was in only eight weeks of time, she was able to see improved results with a significant age-related change over the course of just eight weeks. And so that might add more data to say that stress management might be one of those things that is having an effect. I would say, in our datasets, that is a reoccurring theme, although we don’t know exactly.

Dr. Weitz:            Yeah. She actually didn’t use specific adaptogens for adrenals. She essentially used this greens type powder that contains a bunch of healthy phytonutrients.

Ryan:                     Absolutely. Yeah. I believe that’s a Metagenics product and I think the same with the probiotic. But, yeah, absolutely. But I think the idea was that creating sort of a diet nutrition program along with exercise, sort of a whole lifestyle program to reverse the aging process. And again, we welcome any of those new studies, which are coming out. And we have a couple that are coming out as well. One of the ones that we’re actually just finishing this week is one on some Quicksilver-related products and supplements.  We’ve also looked at things like senolytics such as dasatinib and quercetin. And so as these things start to come out over the next few weeks, we’re going to get them out and information to everyone so we can start figuring out what’s going to change these markers for the better, because again, if you change them, then you’re going to improve your health significantly.

Dr. Weitz:            Since growth hormone is potentially correlated with worse outcome, what do we know about some of the other hormones like estrogen, testosterone?

Ryan:                     Yeah, unfortunately, woefully little. And that is not probably surprising to most people because the way that we’re getting these datasets is via big institutions, things like the Framingham Heart Study, some of these big cohorts that have had samples tested 50, 60 years ago.  Unfortunately, a lot of those same data sets don’t do hormone levels. They don’t even measure them in some of these clinical investigations. And so those data sets are hard to come by. The good news is that the majority of the data sets that we’re getting, most of those people are on hormone replacement. So we’re building those data sets. But unfortunately, we don’t know much right now about estrogens, progesterones, androgens although I will say that we are starting to see an unfortunate maybe negative trend for people who have high levels of androgens particularly over the, I would say, the typical standard reference range by significant amounts. It looks to be increasing or accelerating the aging process. So bodybuilders in particular, I would say, we get some really advanced ages for those people who use significant androgens.

Dr. Weitz:            So we have hormones. What do we know about in terms of food, in terms of… I know you’ve mentioned something about a Mediterranean diet. I’m interested in a lot of times when it comes to discussions about diet and nutrition, one of the issues comes up in terms of what types of macronutrients should we be recommending in particular? And we only have three macronutrients. And so we know that sugar and carbohydrates can be correlated with diabetes and cancer.  And yet, there’s some information that especially Dr. Longo seems to talk about this a lot and Dr. Sinclair did that protein is associated with increased cancer. And saturated fat has been associated with heart disease. So what do we really know about longevity and macronutrients?

Ryan:                     Yeah. So again, as it relates to epigenetic methylation, not a lot. The majority of the research that has been done there has been done by a Stanford researcher, Dr. Lucia Aronica, who did a study called the Diet Fit Study, which compared sort of those low carb diets versus other diets. And so, I think that that data has not been fully analyzed yet. But I do think that we probably tend to see a trend in our datasets to show that the ketogenic diets are positive.  And so, I would say low calorie is definitively good. We already talked about that caloric restriction trial. Low calorie and periods of caloric restriction to then possibly increased autophagy, I think, are highly effective. But as it relates to Dr. Longo, here we’re actually doing a study with the ProLon fasting mimicking diet as well right now, to see how that works. And I think that in our initial data, what we’re seeing is that the prolonged fasting mimicking diet does indeed work or over time.  We’re seeing that caloric restriction absolutely worked. But we’re not seeing the same data, the same positive data for actually time restricted feeding. So people might like to eat between those six-hour windows. And unfortunately, we’re not seeing the same benefit unless they’re also, by doing that, doing some type of caloric constriction.

And so we don’t know a lot about the macronutrients yet. Soon, we actually think that we’ll be able to diagnose or to tell you how much of each macronutrient you’ve actually had by just looking at your methylation. But we’re not sure how it affects longevity. And so I will say that caloric restriction is the only thing we know from a diet perspective that’s great. And in the Mediterranean diet as well can reduce that aging process.  And as you might’ve saw on one of those big slides, if you’re trying to improve your aging rates, consumption of at least one drink of beer or wine per week is great along with more consumption of fish, where if we try and change the intrinsic, we would suggest at least eating poultry two or three times a week. And so I would say that, in and of itself, protein doesn’t look to be bad as long as it’s not in excess.

Dr. Weitz:            Interesting. I recently talked to Dr. Antoun from L-Nutra who works with Dr. Longo. And he said that their data shows that fasting and the fasting mimicking diet are beneficial, but that caloric restriction is not. And I’d also like to point out that Dr. Walford, who was the guy who really put caloric restriction on the map is the professor from UCLA who participated in that. What was the name of that trial where he was locked in that space in Arizona for two years?

Ryan:                   Yeah. I don’t recall the name. But I know the one that you’re referencing.

Dr. Weitz:            The Biosphere 2.  And so it turned out that they weren’t able to produce the right amount of food. And so everybody got a lot less calories. And he looked horrible when he got out, and it turns out that he actually didn’t live that long. I think he died of ALS in his later 70s. And so some people point to that as an indication that a caloric restriction might not be that beneficial obviously and N of one, it doesn’t really mean that much but-

Ryan:                   Exactly. And that’s why I love the calorie trial so much is because it’s over the course of a long period of time, two years. It’s mild calorie restriction. It’s 21%.

Dr. Weitz:            What is… 10%?

Ryan:                   20% caloric restriction. And it’s done in several thousand patients. And so it is one of the first and largest studies of its kind on caloric restriction. And I’ll throw it up here again in case it’s helpful. But again, this goes to show you over the course of 24 months the change in biological aging for caloric restriction, which again, if you’re starting here at baseline, you can see that they’re going even less than half a year, versus those who were not, who are in fast agers aging over two years and in slow agers aging a little bit less.  And so again, this is, I would say, just to start of the data analyzing that’s going to happen as a result of the calorie trial. But we do know that it slows aging and extends lifespan.

Dr. Weitz:            What do we know about exercise and its effect on biological aging?

Ryan:                   Again, woefully little. But we do know a couple of things, which is that there is probably a sweet spot which is that people who over-exercise, marathon runners, even professional athletes tend to maybe have worse biological aging. And we think that’s because they have so much reactive oxygen species. They’re sort of over-training. But we also understand that people who don’t exercise essentially then might also have the reverse. And so for most things, even as I mentioned with alcohol, there seems to be a sweet spot where some is good, but too much is bad.  You’re trying to really bind those. It can be difficult. But, again, I don’t think that that diminishes anything of the testing, particularly, even things the DunedinPoAm pace of aging allow you to do those investigations on the one person that matters for it which is you. You can take a test. You can implement some type of intervention. Let’s just say you want to try caloric restriction. And then retest to see how your pace of aging is going.  And we know that by changing that metric, you change those phenotypic outcomes. You change IQ. You change your sarcopenia risk. You change your risk for dementia or cognitive impairments. And so that we know. And so we also know that is a very precise test, which has a lot of the accuracy between samples. So even over the course of eight to 12 weeks, you can get a good idea of how it’s affecting you personally. And that’s really what I encourage everyone to do, is to start getting that information on yourself and then making the necessary changes to reverse your aging process.

Dr. Weitz:            So you can make an intervention and retest in two to three months and see a significant change potentially.

Ryan:                   Absolutely. And the algorithms are becoming even more accurate. We always talk about the sensitivity. Even with things like telomeres, people wouldn’t use the recommended within a period of a year. And for some of the algorithms, we definitely don’t recommend it over a period of year. But the Dunedin pace of aging in particular is very, very accurate. And so for that one, even over the course of just a few weeks, you can see a significant amount of change.

Dr. Weitz:            And what do we know about rapamycin?

Ryan:                   Yeah. So a good bit, actually. So we’ve done a rapamycin trial. And, unfortunately, we haven’t seen any changes or much changes in blood-based methylation. It’s been significant. We’re still increasing our numbers for those investigations. But we do see a change in other types of tissue, which I think is one of the other things about methylation, which is really, really important is that every cell is going to have a different methylation signature. They’re also going to have different aging rates.  If we were to test your brain, we would get much, much lower ages than if we tested your blood. And if we tested your breast tissue, we would get a much, much higher ages. So all that to say that the tissue type is important. And so for rapamycin, we don’t see changes in blood. But we do see changes in saliva. And part of the reason being is it in saliva, we have epithelial tissue that we don’t have in blood. And so we are seeing positive, beneficial changes in rapamycin. But only in saliva and not in blood, which is interesting.

Dr. Weitz:            Is biological aging correlated with mTOR?

Ryan:                   So unfortunately, we don’t have the data. I should say, as I mentioned, in some tissues, particularly liver and epithelial tissue and in skin tissue, the answer would be yes. Rapamycin as an mTOR inhibitor would then decrease the aging of all of those tissues. And so, we do know that mTOR expression levels when inhibited tend to reverse that aging process in most tissues and in most animals.  But again, that’s really the only mTOR inhibitor that’s been looked at. We’re also doing a couple transplant-related studies who have been on immunosuppressive drugs. A lot of mTOR inhibitors are, hopefully, are going to be able to use that for more data as well.

Dr. Weitz:            What do we know about nutritional supplements to promote aging?

Ryan:                   So not probably unsurprisingly, vitamin D is one that has a massive impact, particularly in overweight individuals that can reverse epigenetic age by 1.8 or 1.9 years over the course of just 16 weeks at a concentration of four to 5,000 IU per day. We’re seeing positive things with things like in NAD-related therapies. All the data still needs to be built out. We’re seeing positive things with methylation support supplements like for instance, L-methylfolate or methylcobalamin in people with certain genetic polymorphisms.  We’re seeing that polyphenols and things like ECGC or citrus bergamot, some of those flavonols can actually help as well. And so we are learning a lot more about those nutritional categories and actually about to publish too a very interesting sort of supplement trials in the near future, which I can’t speculate on now, but are very, very exciting.

Dr. Weitz:            Do we know about fish oil?

Ryan:                   So, yeah. Actually, one of, I would say, probably the best second generation algorithm, GrimAge, is the one that is able to predict death. And in that algorithm and some of those datasets, they were able to correlate higher levels of omega-3 to essentially better response or lower biological agents although in other datasets, they haven’t seen that relationship. And again, there’s been more data coming out now that says, “Maybe, it will not increase your life span.”  I think that we still don’t have enough data, particularly because there’s so much variation even between fish oil supplementation. How much bioavailability you have? How much EPA to DHEA? So unfortunately, that standardized study has not been done. But the GrimAge did report a positive association with fish oils and omega-3s.

Dr. Weitz:            What about supplements that increase NAD production?

Ryan:                   Yeah, so, as I mentioned, we were seeing positive correlations between people who are taking nicotinamide riboside, nicotinamide mononucleotide and/or doing NAD infusions. And so that’s in our dataset where we’re sort of looking at people who do versus people who don’t, which is not, again, the best study. It is informative. But it’s not the best study because probably a lot of those people who are taking NAD-related supplements are also those who were probably the most interested in their own health. So it’s a big confounding factor. But we are seeing a positive relationship between those people who were taking NAD-related supplementation and having sort of a better biological age.

Dr. Weitz:            Do we know anything about NR versus NMR? And do we know anything about dosage?

Ryan:                   Not at all. And I think the doses of NMN are sort of all over the place. And the nicotinamide riboside is a little bit more concrete. But we still don’t know anything about bioavailability. And so without some of that knowledge, it’s going to be hard for us to control and to compare the two back-to-back. And so I’m really hoping a lot of those companies like Tru Niagen and anyone doing NMN will start to get that bioavailability data.

Dr. Weitz:            What about that form of Astragalus that’s supposedly promotes longevity.

Ryan:                   So we don’t know, I should say.

Dr. Weitz:            The TA-65, I think.

Ryan:                   Yeah. TA-65, in particular, is supposed to increase telomerase and telomeres length. And we actually reached out to them for a study to see if we might be able to test their product with some of our telomeres length measurements. And I don’t think we had any interest. But we’d be interested to know as well.

Dr. Weitz:            All right. We have any other questions. Somebody was asking, do you have any special offers for a webinar participants to take the test?

Ryan:                   Unfortunately, we don’t have one now. For any of our practitioners who want to get started though we give sort of a big discount on their first orders. And so if you have any questions or would like to get started on our testing, please reach out to us directly at support@trudiagnostic.com or reach out to me atryan@trudiagnostic.com.  And we’ll hopefully get you started. And I think the best way to sort of see all the benefit is to go through it yourself. And so we’d love to have you do that. Please reach out to us and we’d love to help you.

Dr. Weitz:            And so, what is the process? Can you explain what the process is? Basically, we have the patients go online, register, and then they get sent the kit, or do you send us kits or-

Ryan:                   Yeah. So we can do either. We can drop ship it to the patient, or we can ship it to a clinic. And so if you don’t want the patients to use a finger stick blood spot test, you can collect a purple top EDTA tube from a venous puncture or you could even extract blood from another tube and put it into our tube. And so there’s a lot of ways that you can do it. It’s a really easy collection process for the patient, just takes usually about five to 10 minutes. Then, you drop it in the mail. And then, we’ll send the results back to you in right around two weeks. And so those actual, those boxes, which are kits contain everything you would need. They’re about the size of an iPhone box. So you can easily store it in your office and then give it to patients whenever they have interests.

Dr. Weitz:            Okay, great. And your website is-

Ryan:                   It’s going to be trudiagnostic.com. T-R-U Diagnostic. And again, if anyone wants to reach out to me via email, my email is ryan@trudiagnostic.com.

Dr. Weitz:            Awesome. Thank you so much, Ryan. That was awesome. A lot of very useful information. Thank you to everybody for joining, and we’ll see you next month.

Ryan:                   Thanks so much. Bye-bye.

Dr. Weitz:            Thank you, listeners, for making it all the way through this episode of the Rational Wellness Podcast. Please, take a few minutes and go to Apple podcasts and give us a five-star ratings and review. That would really help us so more people can find us in their listing of health podcasts.  I’d also like to let everybody know that I now have a few openings for new clients for nutritional consultations. If you’re interested, please call my office in Santa Monica at 310-395-3111. That’s 310-395-3111. And take one of the few openings we have now for a individual consultation for nutrition with Dr. Ben Weitz. Thank you and see you next week.

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Dr. Peter Kozlowski speaks about How to Unfunc Your Gut with 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

5:00  The gut is so important for our overall health because as Hippocrates told us 3,000 years ago, that all disease begins in the gut.  A lot of things that we do in modern life is damaging to the gut, including EMFs from our phones, stress, our food supply, toxins in the environment, antibiotics, meds, etc.  One of the most important things about the gut is that it is the barrier to keep things out that might harm us, so leaky gut is so problematic.  Once you get inflammation in the body, it can go anywhere and that’s why you get different symptoms when people get SIBO or candida or gluten sensitivity.  We also have 3 to 5 lbs of bacteria living in our microbiome and these bacteria interact with our genes and they help to keep us healthy.  We are mostly bacteria.

8:23  Dr. Kozlowski in his book Unfunc Your Gut discusses the important role that mental, emotional and spiritual health play in our gut health. Your nervous system talks to your gut through the vagus nerve. This is largely through our autonomic nervous system and we tend to be very sympathetic nervous system dominant.  The more we can activate our parasympathetic nervous system through meditation, therapy, heart rate variability, gratitude, acupuncture, breathing, the better your gut is going to function.

19:40  Food sensitivities.  Dr. Kozlowski does not find food sensitivity tests helpful since what typically comes out as a positive is based on what foods they have been eating for the last few months.  Most people who show multiple food sensitivities have open gap junctions, ie. leaky gut. He prefers to place patients on a 21 day elimination diet that eliminates at least gluten, dairy, soy, corn, eggs, and sugar.  On a full elimination diet, he will also cut out beef, pork, shellfish, processed meats, and coffee.   After 21 days, the eliminated foods will be reintroduced one by one. Foods that they still can’t tolerate, they should work on improving their gut health and then test those foods back in 6 months.

28:14  The healthiest diet for longevity is some version of the Mediterranean diet. Dr. Kozlowski recommends that people eat 9-12 servings of vegetables and fruits per day and a serving is 1 cup raw or 1/2 cup cooked.  In our standard American diet we don’t eat many vegetables.  In our typical breakfast of pancakes, bacon, breakfast sandwiches, cereal, etc. we typically don’t eat any vegetables. And then lunch is pizza or hotdogs or sandwiches, no vegetables again. And then perhaps there’s a side of broccoli at dinner.  So we’re eating one to three servings of vegetables instead of 9-12 servings of vegetables and fruits per day that he recommends.  We should definitely avoid sugar, processed foods, and processed vegetable oils in our diet.

31:25  The microbiome.  When you don’t take care of your garden, weeds grow and this happens with our microbiome.  Antibiotics are the easiest way to screw up your microbiome and one round of broad spectrum antibiotics can wipe out half your microbiome.  And then weeds take over your garden, which is dysbiosis.  Dr. Kozlowski prefers to do a stool test and urine testing to see what might be overgrown or out of balance in your microbiome.  It is a bad strategy to give probiotics to patients with SIBO or dysbiosis or candida, since you need to pull out the weeds first before trying to grow back the healthy bacteria. This is typically done through taking herbs like grapefruit seed extract or uva ursi or silver or berberine or oil of oregano or caprylic acid or garlic, or you can use the elemental diet to starve the dysbiotic bacteria.  Dr. Kozlowski likes to order the stool test from Doctor’s Data, which tells you which natural products will likely be effective against whatever is overgrown in your gut. He often uses combination supplements such as FC-Cidal, Dysbiocide, and A.D.P. from Biotics Research or Candibactin AR and BR from Metagenics.  He also likes to use Biocidin, which has the longest research behind it.  If the gut lining is inflamed, Dr. Kozlowski will use L-glutamine 5 gm 3 times per day. He may use high dose fish oil or GLA. He may recommend HCL, digestive enzymes, and/or ox bile.  They may need gall bladder support. His favorite SIBO protocol involves taking the herbs two weeks on, one week off for a total of nine weeks. For re-growing the microbiome, Dr. Kozlowski prefers to use prebiotics like Arabinogalactan or inulin and prebiotic foods like banana, asparagus, and artichokes rather than taking probiotics. 

Dr. Peter Kozlowski is a medical doctor who transitioned to Functional Medicine as an intern in medical school. He has trained with leaders in the Functional Medicine field, including Dr. Mark Hyman and Dr. Deepak Chopra. Dr. Kozlowski’s unique take on gut health is described in his new book, Unfunc Your Gut.

Dr. Ben Weitz is available for 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.

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. Today, our topic is gut health with Dr. Peter Kozlowski. Dr. Peter Kozlowski, he will give his unique take on gut health as described in his new book, Unfunc Your Gut. Dr. Kozlowski started out as a family practice MD, but transitioned to functional medicine as an intern. He has trained with leaders in the functional medicine field, including Dr. Mark Hyman and Dr. Deepak Chopra. Dr. Kozlowski, thank you so much for joining us today.

Dr. Kozlowski:                    It’s an honor. Thank you for having me.

Dr. Weitz:                           Good. Good. Good. So you’re speaking to us from Montana. How are things in Montana right now?

Dr. Kozlowski:                    I think we’re on like day number 20 over 90 degrees. So, hotter than normal here.

Dr. Weitz:                           Yeah. But climate change doesn’t exist.

Dr. Kozlowski:                    Yeah.

Dr. Weitz:                           So since you started off as a functional medicine MD, how did you find your way to functional medicine?

Dr. Kozlowski:                    Completely randomly. I just tell people that I got lucky. The majority of practitioners that I know in the functional medicine world usually got into it because they got sick themselves and they tried the traditional route and they couldn’t get better, so they found functional medicine and then decided to use that in their practice.  For me, I was an intern in family practice residency. And as an intern or as a resident, you do different rotations every month. So one month we focus on clinics, outpatient, inpatient, cardiology, OB/GYN, and you’re constantly being trained by different physicians. And when you’re on the inpatient service, every week, there’s somebody new that teaches you.  

And we had one doctor that every patient that was hospitalized, he would put them on a multi-vitamin and vitamin D. And we, as residents, thought it was ridiculous and used to make fun of him that he would make us write those kinds of orders because nobody else did it and we just didn’t get it. So I was working with him on… It was a Sunday night at like 2:00 AM and we had some downtime and I just asked him, I was like, “Why are you weird? Why are you different?”  And he’s like, “I’m studying something called functional medicine.” And I was like, “What is that?” And he took me to the IFM website and it just took off from there. I looked at it, I was like, “This looks pretty interesting.” They require you to go do CME during residency. So I was like, “Why not go check this out?” And within the first hour of the first conference, I just couldn’t look at medicine the same. It was all taught from a science, biochemistry, a physiology level. I couldn’t really argue with it, and it just made sense to me.

And then another thing was, at this conference, there was doctors that were from every profession from chiropractic, acupuncture, ophthalmology, cardiology, neurology, and they’re all here. And I was like… I didn’t get it. I was like, “What are you guys doing here?” And they were like, “This is the future of medicine.” And I heard that over and over and over.  So I left that conference and just really with my brain overloaded, but I was like, “I’m going to slowly focus my career on this.” And I continued throughout residency to go to conference, to work on my certification and got invited to do away rotation. So I left residency for like a month at a time to go work with some of the leaders in the field, and I would just follow them around.  And it wasn’t just the doctors. I would follow around the staff, the nutritionist, the health coach, the life coach, because everything was new to me. It was a completely different approach than I had learned in residency. So I was learning from everybody and I just took notes. And when I graduated, I started my own practice and I’ve been out on my own for seven years now.

Dr. Weitz:                            Cool. So why is the gut so important to our overall health?

Dr. Kozlowski:                    Yeah. So Hippocrates said it 3,000 years ago, right? All disease begins in the gut. And what I always tell people is, basically, since he said that, everything we’ve done is pretty damaging to the gut. With our phones, with stress, with what we’ve done to our food supply, our environment, antibiotics, meds, all of that stuff is damaging our gut.  But the reason, the true reason that it’s the key to our health is, in my opinion, because the gut is the gateway into your body. So when we say gut, it’s a long tube that starts with the mouth and ends with the anus, and it has openings on both ends, so it’s literally just a tube. And the inside of that tube is actually considered outside of your body. So if you swallow something and poop it out, it’s never been in your body.  So to me, the gut’s most important job besides digesting and absorbing is to decide what comes in and what stays out. So that’s where a lot of people have heard of this term, leaky gut. That’s pretty much exactly what it means. When your gut’s leaky, the junctions are wide open and anything that’s passing through your gut tube can pass into your body. Now it’s fair game, it’s in your blood, and the blood goes everywhere.  So you could take a hundred patients with SIBO, candida, gluten sensitivity, and they all have different symptoms because the inflammation is in the body and it can go anywhere. That, I think is the biggest reason. And then the secondary one is your microbiome, is that we all have three to five pounds of bacteria growing on the inside of the large intestine, the last part of your gut. And that bacteria constantly talks to us.  We, as humans have about 23,000 genes. They’ve found over 20 million bacterial genes in our gut. So one of my favorite T-shirts that I have says, “Mostly microbe,” that we’re mostly bacteria. And those bacteria, they develop, they start when we’re born and then we can either keep them healthy through our diet and lifestyle or we can damage them through our diet and lifestyle. So those are the two reasons why the gut is the key to your health.

Dr. Weitz:                            Yeah. I certainly know all about the importance of the microbiome and there’s incredible amount of research going on. But one thing I always find interesting is there are people who do not have a colon, they had Crohn’s disease or ulcerative colitis, and they had their colon cut out. And yet they continue to thrive, probably not ideally, but I’m always amazed about that.

Dr. Kozlowski:                    Yeah. I think it just proves the point of how resilient our bodies are, right? I assume if your large intestine gets cut out, your microbiome just starts to grow at the end of your small intestine and your body adjusts.

Dr. Weitz:                            Yeah. I don’t know. It’s a question we need to answer one of these days. So in your book, Unfunc Your Gut, in the beginning, you talk about stress, which is really important and often not talked about. So how does our mental, emotional, and spiritual health play, or what factor does that play in our gut health?

Dr. Kozlowski:                    So, spoiler alert, that’s the big secret that I reveal in the book is that your mental, emotional, spiritual health is the most important component. And that I learned through my own story, but more in my… I learned it from my patients because one of my faults is that I’m a perfectionist. So I don’t really think about the patients that get better, I only focus on the ones that didn’t.  And trying to figure out why could I put 10 people on a CBO Protocol and half get better and half don’t. And what I started to see over and over, it was usually their mental, emotional, spiritual health, which other terms are anxiety, depression, trauma. To me, I like mental, emotional, spiritual health.  But this, just like everything else in functional medicine, and there’s science behind it; and the main reason, anatomically, why that is because your gut, that tube is surrounded by a nervous system called the enteric nervous system. There’s 200-250 million neurons in that nervous system, more than in your brain or spinal cord or anywhere else.  That nervous system talks to your gut, but then it also sends signals to your brain and your brain sends signals to your gut. So that whole gut-brain connection that people talk about, it’s between the two nervous systems; your central and your enteric. Those systems are connected by the vagus nerve, that’s one of your cranial nerves. And this is where the mental, emotional, spiritual component comes in.

Your vagus nerve runs on your autonomic nervous system, which is your automatic nervous system, which is divided into two responses; sympathetic and parasympathetic. Sympathetic is fight-or-flight. So that is hiking in Montana, you see a bear and you want to escape, all the blood goes to your muscles and brain to try to figure out how to get away. Then when you’re sitting by the campfire, you go into parasympathetic and you rest and digest your food.  People right now, nowadays, are living as if they’re running from a bear 24/7. We wake up, we go straight to our phone, we check our email, our texts, we check the news, we sit down for breakfast, we’re reading our phone or watching the news. And so we’re just constantly activating that sympathetic nervous system, which is sending signals down your vagus nerve to your gut to tell you to not digest, to not absorb. It shuts down your gut bacteria. So that is the connection.  So the more that someone can activate their parasympathetic nervous system through things like meditation, therapy, heart rate variability, gratitude, acupuncture, there is a lot of ways to do it, just breathing, the better your gut is going to function. And then treating something like candida or dysbiosis or SIBO is much easier.

Dr. Weitz:                           Yeah. Actually, this is a device that uses vibrations and it helps get you into a parasympathetic mode as well.

Dr. Kozlowski:                    Oh, excellent.

Dr. Weitz:                           Yeah. Yeah.

Dr. Kozlowski:                    What’s it called?

Dr. Weitz:                            The Apollo.

Dr. Kozlowski:                    Okay. I’ll take a look at that.

Dr. Weitz:                            Yeah. So what do we do about how stress, our mental, emotional spiritual health affects our gut health? You just hinted at it by saying we got to get out of being in sympathetic mode all the time, but what else do we do? If your emotional health is affecting your gut health, what can you do?

Dr. Kozlowski:                    Yeah, the first step is just admitting there’s a problem. My own personal story is I’m in recovery and I used alcohol as a coping mechanism, and so that’s where I learned mental, emotional, spiritual health personally. But what I’ve seen over and over is, as someone who’s spent a long time in denial, usually, you can see it in other people, and so I see it in my patients.  And just having the first… Like I said, the first step is just admitting like, “Okay, maybe my relationship with my parents or with my spouse or my kids or my job could be having a role in my health.” And once you know that, you can’t really un-know it. And even though it’s the most important part of health, it’s the most difficult one for me to help someone with because it’s not what I was trained in. I learned it from my own story, but-

Dr. Weitz:            Interesting. I’ve really been enjoying this discussion, but I’d like to take a minute to tell you about a new product that I’m very excited about. I’d like to tell you about a new wearable called the Apollo. This is a device that can be worn on the wrist or the ankle, and it uses vibrations to stimulate your parasympathetic nervous system. This device has amazing benefits in terms of getting you out of that stressed out sympathetic nervous system and stimulating the parasympathetic nervous system. It has a number of different functions, especially helping you to relax, to focus, to concentrate, get into a deeper meditative state, even to help you sleep, and there’s even a mode to help you wake up. This all occurs through the scientific use of subtle vibrations.

                                For those of you who might be interested in getting the Apollo for yourself to help you reset your nervous system, go to apolloneuro.com and use the affiliate code, Weitz10. That’s my last name, WEITZ10. Now, back to the discussion.

Dr. Kozlowski:                    Every patient that I meet, I encourage them to work with a therapist while they’re working with me.

Dr. Weitz:                           Okay.

Dr. Kozlowski:                    And therapy was a huge part for me to uncover why did I need to use alcohol to deal with my feelings and emotions? And the analogy is like peeling back the layers of an onion. And over time, you just get deeper and deeper and figuring out what’s underlying that. And so that takes… I mean, it’s hard. It’s not easy, so I get why people don’t want to do it. It would be a lot easier to just find the right supplements to take or find the right procedure or treatment, whatever. This is the real work.  And for most people, it starts when we’re children. Trauma is… I have the best definition I’ve heard of trauma, is trauma is anything less than nurturing. And for a lot of us, it could be your parents working two jobs or working and not being around. And then that can start making you feel like you’re not good enough, and then that affects your gut, and then you start having abdominal symptoms. And then by the time you come into my office, you’re in your 30s, 40s, 50s and there’s autoimmune disease. And it started with something as simple as just being uncomfortable in your own skin, which shut down your gut.

So then the good thing about mental, emotional, spiritual health is there are so many different modalities to use, and it’s about exploring and finding which one works for you. For me, exercise is a big one. I feel much better when I exercise. I do a gratitude list every day with my wife. We usually take a walk in the evening and we always do three things that we’re grateful for. Building connections, helping others, these are things that work for me, but then there’s meditation, prayer. So it’s about exploring what is the right combo for you.

Dr. Weitz:                           Yeah, it’s interesting. I think that there’s a tendency for… When dealing with patients with some of these gut disorders that are not really structural, these functional gut disorders like SIBO and IBS, over the years, because it’s been difficult to get quantitative tests that really show what’s wrong. Typically, if you have a patient with IBS, a traditional gastroenterologist is going to do a colonoscope or an endoscope or a CAT scan, you’re not going to see anything.

Dr. Kozlowski:                    Never.

Dr. Weitz:                           So it’s difficult to see the exact structural reasons for why they’re having the problem. So, for many years, patients with IBS were dismissed as basically having an emotional disorder and given antidepressants and things like that. So there’s, I think, a tendency to try really hard to focus on the physical causes for these conditions. And maybe we’ve gone too far and forgotten that there really are emotional and stress-related issues that affect the gut.

Dr. Kozlowski:                    Yeah, I agree. And I think that there’s just a balance because for the… I mean, a lot of patients that have been diagnosed with IBS that come through with me and we do testing, the most common thing that I find is SIBO, an intestinal overgrowth of your small intestine, or dysbiosis or candida or low stomach acid, leaky gut. And treating those things, to me, I think we have good testing now so there’s tests for all of those conditions, and then there’s treatment plans that work.  I guess my point of my book was just, if that’s not working, if you’ve had the right testing, you’ve had a good treatment plan and it’s still not getting better, in my experience, usually, it’s been the mental, emotional, spiritual health that was the big thing that was missed.

Dr. Weitz:                            Right. Let’s talk about food sensitivities.

Dr. Kozlowski:                    Yeah.

Dr. Weitz:                            To begin with, why do so many people seem to have a lot of food sensitivities these days?

Dr. Kozlowski:                    I think it’s mostly because of what we’ve done to our food supply. Most of the food that we eat is not in the form that it started, that it was created as. It started with the hybridization of wheat in the 1960s. Right now, over 90% of soy and corn are genetically modified in the United States. Cows don’t eat grass. They are put in pens and fed hay and other things.  So we’ve changed the proteins of the majority of the foods that we eat, but we never tested how that would affect human beings. And that is, I think, the biggest reason why food sensitivities are increasing at the rate that they are.

Dr. Weitz:                            Now, there’s lots of sophisticated lab tests to measure food sensitivities that look at IgG, IgM, IgA. Companies like Cyrex, [inaudible 00:20:53] have very sophisticated food sensitivity testing. But you say in your book that you don’t feel like these tests are helpful.

Dr. Kozlowski:                    Yeah. And my experience has been that those tests are helpful for diagnosing leaky gut. And when someone does those… The majority of people that do those tests, it’s typically a log of what they’ve been eating for the last few months. Because if your gap junctions in your gut are open, then those proteins from those foods are going to be getting into your blood and you’re more likely to create an immune response against them.  To me, the gold standard that I’ve always used is an elimination diet, which is 21 days of cutting out the biggest offending foods and then reintroducing them one by one. And that’s another thing that is science-based. And when you have a sensitivity, you create IgG antibodies.  Everything in your body has a half-life. So if you smoke cigarettes, if you take prescription meds, if you drink alcohol, everything has a different half-life, or your hormones, toxins. The half-life of IgG antibodies is around 21 days. So let’s say I react to gluten and I had a bagel for breakfast today, and I have 100 antibodies floating around; if I don’t have any gluten for the next 21 days, that antibody count will drop in half to 50.  When I eat it again on day 22, if my immune system has identified it as an invader, it will attack and create inflammation which can present as symptoms like a headache, abdominal pain, a rash, acne, joint pain, it can present anywhere. So, to me, the best way that I’ve found to diagnose sensitivities, the most reliable, is you cut out the foods and then you add them back in one by one, every two days.

Dr. Weitz:                            Now, there’s different versions of the elimination diet. Some people recommend cutting out two foods or six foods or 10 foods. Which foods do you recommend cutting out?

Dr. Kozlowski:                    So typically, the top five or six offenders are gluten, dairy, soy, corn, eggs, and sugar. In a “full elimination diet”, we also cut out beef, pork, shellfish, processed meats, coffee. And I think there might be one more that I’m missing. I have it listed, the full list in the book.  So I really believe in meeting patients where they’re at. There are some people where if all you’re ready to cut out is your energy drink, that’s better than nothing, right? And if you’re just ready to cut out gluten, I’d rather have you do that than try to do a full elimination diet and quit after a day because you’re going nuts.

Dr. Weitz:                            Right.

Dr. Kozlowski:                    One of the things that I think has happened in our field is that there’s so many restrictive diets out there and there’s so much information out there that’s like, “You have to be paleo or you have to be keto or vegan or Mediterranean.”

To me, I and my patients think I’m nuts, I tell them, I’d rather have you eating fast food if it doesn’t stress you out. If you’re so worried about eating the perfect meal, it’s not going to help. You’re going to shut down your digestion, your cortisol is going to elevate, and you’re not going to get the benefits from that meal. And that’s okay. Like right now, you might not be ready for an elimination diet, but a year from now, you might be.

Dr. Weitz:                            [inaudible 00:24:38] is when they layer one diet on top of the other.

Dr. Kozlowski:                    Right.

Dr. Weitz:                           So they’re following their paleo diet, and then they eliminate high-FODMAP foods, and then they eliminate histamine foods.

Dr. Kozlowski:                    Yeah. Right. Then there’s like three things you can eat.

Dr. Weitz:                           Right.

Dr. Kozlowski:                    I’ve seen that a lot with the sensitivity testing too. People come in, they’ve had the testing and they’re eating like six foods. I believe in a candida diet, a low-FODMAP diet, elimination diet, but in short-term. Right? Some of those diets are too stressful to do long-term.

Dr. Weitz:                           Yeah. Short-term to get rid of symptoms, to help get your condition on the road to healing.

Dr. Kozlowski:                    Exactly.

Dr. Weitz:                           But long-term, you’re going to end up with nutritional deficiencies.

Dr. Kozlowski:                    Right. Yeah, absolutely.

Dr. Weitz:                           So you have patients cut out all these foods for 21 days. And then how often do they put food back and how long do they wait for? How many times a day do they need to eat it?

Dr. Kozlowski:                    Yeah. We’re starting an elimination diet challenge on August 1st on social media, on my Instagram and Facebook. So I’m going to be posting… In my book, we have over 50 recipes to help people, but we’re going to be posting recipes, answering questions, and just hopefully making it easier for people to do.  The way that I approach it is you reintroduce the food, one food at a time, three times that day. So day 22, you introduce, let’s say, gluten three times. You don’t add anything else new. You wait, day 23. If nothing’s happened in those two days, then you start the next food. So we’re doing every two days. A classic reaction to dairy is like, everything’s fine on day 22. But day 23, you wake up and your face is broken out in acne or something.  So, we do one food every two days, three servings on that day. If you have a reaction, you wait until the reaction’s gone to start the next food. For some people, it could be a couple of days. I’ve seen it be a week. And you use a tracking journal, which we have a copy of, and you just write down what happened. And the symptoms, if you went into an elimination diet because of migraines, when you have dairy and you react to it, you might get joint pain. You might not get the exact symptom that you’re looking for, but it still means it’s inflaming your body.

Dr. Weitz:                           If somebody has a pretty strong reaction to gluten, will you have them try it again in the future or will you just say, “Just avoid gluten?”

Dr. Kozlowski:                    Yeah. I tell people to try it again. What I tell them is to Unfunc their gut, get their gut right, and then try again in about six months. I mean, it can change. I’ve seen it change. What you’re sensitive to, you might not be sensitive to in the future. So my advice always is to try, especially if you’re missing the food… You meet a lot of people that are like, “I don’t care about gluten. I don’t ever want to eat it again.” And they’re fine. But then, I think more people are like, “Well, when can I eat this again?” So I always encourage trying.

Dr. Weitz:                            Sure. So what’s the healthiest diet for most people to follow for longevity?

Dr. Kozlowski:                    I keep it very, very simple. I give two main goals. The most evidence, what I’ve seen is behind the Mediterranean diet. But to keep things simple, what I encourage people to do is to eat 9-12 servings of vegetables and fruit a day. And if you’re eating that… A serving is a cup raw or a half-cup cooked. And if you’re eating that many vegetables and fruit in a day, there’s not room for the other stuff. You’re full from everything else.  And so, in our standard American diet, our typical breakfast of pancakes, bacon, breakfast sandwiches, all this stuff, cereal, we don’t eat any vegetables. And then lunch is pizza or hotdogs or sandwiches, no vegetables again. And then there’s a side of broccoli at dinner. So we’re eating one to three probably, the average American. Whereas I encourage people to shoot for 9-12.

So I think that’s an easy… I mean, it’s not easy for people to do, but it’s easy to remember like, “Okay, if I’m going to try to eat well, what should I do?” And it’s just like, “Increase that intake of natural vegetables and fruit.” And then I think that everybody should do an elimination diet because you might not even have symptoms right now, but you might be sensitive to some things. Besides the Mediterranean diet, that’s what I would recommend for people.  But I’ve met people that they swear by vegan, they swear by paleo, they swear by keto. That’s fine. I don’t tell people, “No. If that’s working for you, you have to stop it because I believe in something else.”

Dr. Weitz:                            Right. So in terms of prevention of cancer and cardiovascular disease, what do you think are some of the things to focus on? What foods or food groups or macronutrients, what should we reduce or avoid for most people?

Dr. Kozlowski:                    Sugar.

Dr. Weitz:                            Sugar.

Dr. Kozlowski:                    Yeah. You just cut out sugar, it’ll take you a long, long way.

Dr. Weitz:                            [inaudible 00:30:42].

Dr. Kozlowski:                    And then processed foods and saturated foods.

Dr. Weitz:                            Okay.

Dr. Kozlowski:                    Yeah.

Dr. Weitz:                            What do you mean? Saturated fat? Is that what you mean?

Dr. Kozlowski:                    Yeah. Yes. Yeah.

Dr. Weitz:                            Okay. Lots of controversy over what causes heart disease. Does saturated fat really cause heart disease? Does it raise your LDL Why? How does saturated fat do that?

Dr. Kozlowski:                    Sorry. So I misspoke. Yeah, I agree with you. So it’s like the trans fats, the fats that are in fast food and in French fries and the processed vegetable oils and canola oils and all that stuff.

Dr. Weitz:                            Right. Okay. Can you talk about the microbiome and what’s the best way to test for it, and what do we do to optimize our microbiome?

Dr. Kozlowski:                    Yeah. Your microbiome, the analogy that I really like is it’s like your own garden, like your garden at home. And so, in that analogy, the probiotics are the plants of your garden. Fibers and good sugars are the fertilizer of your garden. But what happens when you don’t take care of your garden is weeds grow, right? And that’s what happens in our guts. And that’s where you can get dysbiosis, candida, SIBO, those things.  So I think the best way to screw up your microbiome is antibiotics because antibiotics are tablets that were designed to kill bacteria. And where do you put them typically? In a tube that has five pounds of bacteria in it. So just taking antibiotics once can wipe out up to half of your microbiome. And then if half your garden is wiped out, what happens? Weeds start to take over, right?  And we’re being exposed to all these different weeds every day, all the time. And if your garden’s empty, those weeds see this fertile soil and will take over. So antibiotics are a big thing. A microbiome in general, because of that analogy, even though I’m known for gut health, I don’t typically start probiotics. I prefer to do it through food.

Probiotics, there’s a lot of discussion of do they actually stay in your gut? Where do they get broken down? How long do the effects last? But also, if there’s weeds overgrowing in your garden, you wouldn’t go to the nursery and buy more plants, right? You would pull the weeds out. And so pulling the weeds out is, in my experience, done through stool and urine-testing to identify what’s growing in there, and then treating that to make sure it goes away, and then focusing on pre and probiotic foods.  The other thing that’s happened to me is the most common condition that I treat is SIBO, and that’s when your microbiome, which should be living in your large intestine, is now living in your small intestine. And your small intestine is where you should be absorbing your nutrients and digesting some food, should not be covered in bacteria. So it’s bacteria overgrowing.  And if you have SIBO and you start a probiotic, you can actually get worse because you’re feeding the problem. And in our general society, if you tell someone you’ve got abdominal pain, they’re going to tell you to eat more fiber and take a probiotic, which for a lot of people works but if it doesn’t and you’re feeling worse, that could be a sign that you have SIBO.  So, stool testing, a stool analysis tells us what’s growing in your garden, how inflamed your gut is, how well your gut bacteria eat, do you have parasites?

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Dr. Weitz:                            So, Peter, what do you use to treat dysbiosis or bacterial overgrowth?

Dr. Kozlowski:                    Yeah, it varies in everybody. The three options typically are antibiotics, which I usually try to push people away from just due to all the side effects; a natural herbal approach, which I’ll talk a little bit more about; and then a third, and I call it the nuclear option, is an elemental diet, a liquid diet for two or three weeks. That’s usually… I’ve only used in either people that can’t get an ulcerative colitis under control or people that have failed treatment with SIBO multiple times, I’ll try that.  I’ve had a few patients over the years that have just started with an elemental diet, but that’s pretty rare because it’s so difficult. But when it comes to the herbal approach, so if you do a stool analysis and they find dysbiotic bacteria, they’ll do sensitivity testing. So they’ll tell you that whatever species is growing inside you reacts, responds to grapefruit seed extract or uva ursi or silver or berberine or oil of oregano. So if you have that information, you can really target your treatment because you’ll see resistant patterns on there.

Dr. Weitz:                           Yeah. Some of the stool-test companies do and others don’t. What stool tests do you usually order?

Dr. Kozlowski:                    Majority of the time I use Doctor’s Data.

Dr. Weitz:                           Okay.

Dr. Kozlowski:                    Because I’ve just found they always test more herbs than anybody else. So I like to see the resistance and sensitivity patterns. And my experience is that they seem to be better at catching candida and yeast overgrowth than other labs that I’ve used. So I like Doctor’s Data a lot.

Dr. Weitz:                           I think a lot of us are using other stool tests that don’t necessarily test those. So if you don’t have those, how do you decide what herbs to use?

Dr. Kozlowski:                    It’s a shotgun approach. So you can pick the herbs that are the most effective, and that’s some of that list, oil of oregano, uva ursi, silver, grapefruit seed extract, caprylic acid, garlic. These are all things that you can use. And when I’m treating, let’s say, SIBO, which with SIBO, through breath testing, you can get a yes or no answer. “Yes, you have it.” “No, you don’t.” But you have no clue what’s overgrowing.  So you don’t know if that’s probiotics overgrowing, you don’t know if that’s yeast overgrowing, you don’t know if it’s dysbiosis growing. So that’s a situation where we’re definitely using a shotgun approach. We’re just doing a broad spectrum.

Dr. Weitz:                           Well, a little bit, because if it’s methane, you know it’s archaea. If it’s hydrogen-

Dr. Kozlowski:                    That’s true.

Dr. Weitz:                           It’s likely different organisms. And now we have the hydrogen sulfide, which some say it’s the type of organisms that are involved in that.

Dr. Kozlowski:                    So when I’m treating those, I typically use a supplement from Biotics Research, FC-Cidal, Dysbiocide, and A.D.P. That combination of the three, that I’ve used for the last few years, mostly. Metagenics makes a combo product called CandiBactin.

Dr. Weitz:                            [inaudible 00:39:41].

Dr. Kozlowski:                    Yep, exactly. And then Biocidin, I think has the longest research behind it, or at least I’ve used that one the longest. And right now, just with all the things going on in the world, so many things are backordered, so it’s just trying to figure out what’s available and trying that.

Dr. Weitz:                            Yeah.

Dr. Kozlowski:                    Stuff.

Dr. Weitz:                            Yep. Yep. Yep. So, besides herbal antimicrobials, what else will you use?

Dr. Kozlowski:                    So, for dysbiosis, if somebody’s gut lining looks very inflamed, then I might do things to calm the gut lining, and my favorite is glutamine.

Dr. Weitz:                           Okay.

Dr. Kozlowski:                    High dose. Five grams, three times a day. Sometimes just anti-inflammatories like high-dose fish oil or gamma-linolenic acid (GLA), omega-6. So sometimes I’ll do some stuff like that. If somebody we suspect or they have low stomach acid, I will put them on hydrochloric acid. Sometimes we’ll use pancreatic or digestive enzymes, ox bile, gallbladder support. So those are the main things I think that I use.

Dr. Weitz:                           Okay. And do you go through phases of treatment or?

Dr. Kozlowski:                    Usually, my SIBO most common treatment plan is nine weeks where it’s two weeks on, one week off, and you cycle that three times.

Dr. Weitz:                           Okay. With the same herbs each time?

Dr. Kozlowski:                    Mm-hmm (affirmative). Yeah. There’s been times where I’ve tried to use different ones because one of the concerns is if you use the same stuff over and over, there’s obviously resistance. So you can definitely try to cycle it.  But no, typically, I’ll use… At least through the first time through, right? In the first two or three months that we’re trying, then I’ll stick to the same regimen and then either repeat testing or talk to the person and see if they’re not really getting better, then we need to adjust something.

Dr. Weitz:                           Right.

Dr. Kozlowski:                    I always try to take the path of least resistance. So usually, whatever’s going to be the easiest, let’s try that first, assuming the symptoms are not severe. Instead of just throwing everything all at once. It can be overwhelming, I think.

Dr. Weitz:                            Right. So let’s say you have a SIBO patient, you do the nine weeks of herbs. Is treatment done then?

Dr. Kozlowski:                    If they’re better. It depends. If their symptoms have gone away, which happens many times, it’s great, and they move on. And then the next phase is reintroducing the higher FODMAPs because I do like people to stay on a low-FODMAP diet during SIBO treatment.  The interesting thing I’ve found with people that have recovered from SIBO is frequently you’ll hear that there’s one food that they just can’t tolerate. And it’s always different. Every person tells me something different. So it’s just adding them back in the higher FODMAPs and making sure that your body doesn’t react to those still.

Dr. Weitz:                            I know Dr. Pimentel will put the patients on a promotility, prokinetic after he uses antibiotics, to decrease the likelihood that it’ll come back because there’s a whole motility focus. Some natural practitioners will use natural prokinetics.

Dr. Kozlowski:                    Absolutely. Yeah, I definitely agree with that, with the motility activators. I’ve found to be, to me, more important is to make sure the patient’s digesting, that their stomach acid is sufficient because to me, that’s the key, that’s what kills off the bacteria. So if you’re not making enough stomach acid, then that’s a pretty high recurrence rate for SIBO.

Dr. Weitz:                            So how do you know if you’re not making enough stomach acid?

Dr. Kozlowski:                    There’s two ways to test that I’ve found to be reliable. And the first one to me, when I first heard about it, I laughed. I thought it sounded kind of ridiculous. It’s called the baking soda test where you mix a quarter teaspoon of baking soda and a few ounces of water, drink it on an empty stomach. Baking soda is basic, your stomach should be acidic. When the bass and the acid meet, it creates an explosion which presents as gas and you start burping, which you should burp in the first three to five minutes.  So when I first heard of that, I was like, “This sounds like a high school chemistry experiment. This sounds ridiculous.” But I’ve actually found it to be pretty reliable. If people don’t burp, then it usually means they don’t have enough acid.

And then the second step is actually supplementing hydrochloric acid. I outline the whole protocol in the book, but you start with one capsule, but you only take it before eating protein. So I tell people in the beginning, just with meat, fish, eggs, your bigger proteins. Definitely not with a smoothie. But you start with one and you take it and then you eat.

A normal reaction would be to get some heartburn, to get some discomfort because you dropped in acid, your stomach’s making acid, there’s too much and it refluxes. An abnormal response to that is to not feel anything or to feel better, that’s a marker that you have low acid. And then the question is how bad is it? So every two days, we increase the dose from one to two, two to three, until you get some heartburn or discomfort. And let’s say that happens after you took three, then your dose is two. And that’s what I would have you on.

And the most common question that I get is, “Well, how long am I going to be on this?” And to me, it usually depends. What I tell people is it depends on the underlying cause. With majority of people that I’ve seen, the biggest cause of low stomach acid besides aging is our stress and the sympathetic nervous system. So if that’s activated, you’re shutting down your acid production. So when your parasympathetic gets activated, then you’ll start making more. And then let’s say you’ve been on two capsules; all of a sudden, you take it one day and it kind of burns, you know it’s time to cut back or come off of it.

Dr. Weitz:                            And you don’t like to use probiotics. You use what? Fermented foods?

Dr. Kozlowski:                    For stimulating the microbiome?

Dr. Weitz:                            Yeah.

Dr. Kozlowski:                    Yeah. I prefer focusing on pre and probiotics and foods. So fermented foods, sauerkraut, things like that, dairy or dairy alternatives, and then prebiotics. I believe more in prebiotics, so things like banana, asparagus, artichokes, things like that, that are going to feed your microbiome.  And to me, if you’re going to supplement one, I usually actually go with prebiotics just to stimulate your bacteria to grow. I can’t say that I don’t ever use them. In general, supplements I think should be supplements. And so what I tell people frequently is if you’re traveling or if your diet sucks that day, you didn’t have anything fermented, then take a probiotic. But if your diet is strong, then you don’t need it, in my opinion.

Dr. Weitz:                            What’s your favorite prebiotic product?

Dr. Kozlowski:                    Arabinogalactan or inulin? Inulin is typically in a powder. Arabinogalactan comes in capsules and powder, so sometimes that’s easier. If you take your pre and probiotic together, they call it a symbiotic. So those are the two big ones that I would use.

Dr. Weitz:                            Okay. I think that’s pretty much a wrap, Dr. Kozlowski. Have final thoughts you want to leave our viewers and listeners?

Dr. Kozlowski:                    No, thank you very much for having me. And if I can give one piece of advice, it is to stay in the present moment. There is an ancient philosopher that said anxiety is worrying about the future, depression is worrying about the past, so what’s the best treatment is the present moment. And I think so much of our lives are taking us out of the present moment, so the best thing you can do is to get back into it and your gut will heal and then all the protocols or supplements or whatever you need to treat whatever’s going on will be much more effective.

Dr. Weitz:                           That’s great. How can listeners and viewers find out more about you, your book, et cetera?

Dr. Kozlowski:                    Yeah. So my book, Unfunc Your Gut, with a C, Unfunc with a C, you can get it anywhere on Amazon, Barnes & Noble, your local bookstores, so it’s pretty available. To contact me or to learn more about me, doc-koz.com, D-O-C dash K-O-Z dot-com. And I’m on Instagram and Facebook. On Instagram, it’s @doc_koz. And on Facebook, it’s just Peter Kozlowski M.D., which I’ve gotten more active lately and just sharing stuff there.

Dr. Weitz:                           Great. Thanks, doc.

Dr. Kozlowski:                    Yeah. Thank you.

Dr. Weitz:                            Thank you listeners for making it all the way through this episode of the Rational Wellness Podcast. Please take… I’d also like to let everybody know that I now have a few openings for new clients for nutritional consultations. If you’re interested, please call my office in Santa Monica at 310-395-3111. That’s 310-395-3111. And take one of the few openings we have now for an individual consultation for nutrition with Dr. Ben Weitz. Thank you and see you next week.